Electrically Induced Crystal Field Distortion in a Ferroelectric Perovskite Revealed by Electron Paramagnetic Resonance.

The magnetoelectric material has attracted multidisciplinary interest in the past decade for its potential to accommodate various functions. Especially, the external electric field can drive the quantum behaviors of such materials via the spin-electric coupling effect, with the advantages of high spatial resolution and low energy cost. In this work, the spin-electric coupling effect of Mn2+-doped ferroelectric organic-inorganic hybrid perovskite [(CH3)3NCH2Cl]CdCl3 with a large piezoelectric effect was investigated. The electric field manipulation efficiency for the allowed transitions was determined by the pulsed electron paramagnetic resonance. The orientation-included Hamiltonian of the spin-electric coupling effect was obtained via simulating the angle-dependent electric field modulated continuous-wave electron paramagnetic resonance. The results demonstrate that the applied electric field affects not only the principal values of the zero-field splitting tensor but also its principal axis directions. This work proposes and exemplifies a route to understand the spin-electric coupling effect originating from the crystal field imposed on a spin ion being modified by the applied electric field, which may guide the rational screening and designing of hybrid perovskite ferroelectrics that satisfy the efficiency requirement of electric field manipulation of spins in quantum information applications.

Combined SET7/9 and CDK4 inhibition act synergistically against osteosarcoma.

Osteosarcoma is the most common malignant bone tumor. It has a poor prognosis because of a lack of therapeutic targets and strategies. The SET domain-containing lysine-specific methyltransferase, SET7/9, has various functions in different cancer types in tissue-type and signaling context-dependent manners. The role of SET7/9 in osteosarcoma cells is currently controversial and its potential as a therapeutic candidate in osteosarcoma is unknown. In the present study, SET7/9 inhibition or ablation suppressed osteosarcoma cell proliferation by causing G1 arrest. Mechanistically, SET7/9 inhibition disrupted the interaction between cyclin-dependent kinase 4 (CDK4) and cyclin D1, which affected CDK4-cyclin D1 complex function, leading to decreased phosphorylation of retinoblastoma protein. CDK4 was overexpressed in osteosarcoma tissues and was closely related to a poor prognosis in patients with osteosarcoma. We therefore hypothesized that SET7/9 inhibition might increase the sensitivity of osteosarcoma cells to CDK4 inhibitors, potentially decreasing the risk of adverse effects of CDK4 inhibitors. The combination of SET7/9 and CDK4 inhibition enabled dose reductions of both inhibitors and had a synergistic effect against osteosarcoma growth in vivo. Collectively, these findings indicate that SET7/9 plays an oncogenic role in osteosarcoma by regulating CDK4-cyclin D1 complex interaction and function. The combination of SET7/9 and CDK4 inhibition may thus provide a novel effective therapeutic strategy for osteosarcoma with no significant toxicity.

Angular-resolved Rabi oscillations of orthorhombic spins in a Co(II) molecular qubit.

Magnetic molecules are promising candidates for quantum information processing (QIP) due to their tunable electron structures and quantum properties. A high spin Co(II) complex, CoH2dota, is studied for its potential to be used as a quantum bit (qubit) utilizing continuous wave (CW) and pulsed electron paramagnetic resonance (EPR) spectroscopy at low temperature. On the X-band microwave energy scale, the system can be treated as an effective spin 1/2 with a strongly anisotropic g-tensor resulting from the significant spin-orbital coupling. An experimental and theoretical study is conducted to investigate the anisotropic Rabi oscillations of the two magnetically equivalent spin centres with different orientations in a single crystal sample, which aims to verify the relationship between the Rabi frequency and the orientation of the g-tensor. The findings of this study show that an effective quantum manipulation method is developed for orthorhombic spin systems.

Spin-Electric Coupling with Anisotropy-Induced Vanishment and Enhancement in Molecular Ferroelectrics.

Manipulating quantum properties by electric fields using spin-electric coupling (SEC) effects promises spatial addressability. While several studies about inorganic materials showing the SEC functionality have been reported, the vastly tunable crystal structures of molecular ferroelectrics provide a range of rationally designable materials yet to be exploited. In this work, Mn2+-doped molecular ferroelectrics are chosen to experimentally demonstrate the feasibility of achieving the quantum coherent SEC effect in molecular ferroelectrics for the first time. The electric field pulse applied between Hahn-echo pulses in electron paramagnetic resonance (EPR) experiments causes controllable phase shifts via manipulating of the zero-field splitting (ZFS) of the Mn(II) ions. Detailed investigations of the aMn crystal showed unexpected SEC vanishment and enhancement at different crystal orientations, which were elucidated by studying the spin Hamiltonian and magnetic anisotropy. With the enhanced SEC efficiency being achieved (0.68 Hz m/V), this work discovers an emerging material library of molecular ferroelectrics to implement coherent quantum control with selective and tunable SEC effects toward highly scalable quantum gates.

MIR31HG polymorphisms are related to steroid-induced osteonecrosis of femoral head among Chinese Han population.

BACKGROUNDS: MIR31 host gene (MIR31HG) polymorphisms play important roles in the occurrence of osteonecrosis. However, the association of MIR31HG polymorphisms with the risk of steroid-induced osteonecrosis of the femoral head (SONFH) remains unclear. In this study, we aimed to investigate the correlation between MIR31HG polymorphisms and SONFH susceptibility in the Chinese Han population. METHODS: A total of 708 volunteers were recruited to detect the effect of seven single nucleotide polymorphisms (SNPs) in the MIR31HG gene on SONFH risk in the Chinese Han population. Genotyping of MIR31HG polymorphisms was performed using the Agena MassARRAY platform. The odds ratio (OR) and 95% confidence interval (95% CI) were used to evaluate the correlation between MIR31HG polymorphisms and SONFH risk using logistic regression model. RESULTS: According to the results of genetic model, rs10965059 in MIR31HG was significantly correlated with the susceptibility to SONFH (OR = 0.56, p = 0.002). Interestingly, the stratified analysis showed that rs10965059 was associated with the reduced risk of SONFH in subjects aged > 40 years (OR = 0.30, p < 0.001) and male populations (OR = 0.35, p < 0 .001). Moreover, rs10965059 was associated with the reduced risk of bilateral SONFH (OR = 0.50, p = 0.002). Finally, multi-factor dimension reduction (MDR) results showed that the combination of rs1332184, rs72703442, rs2025327, rs55683539, rs2181559, rs10965059 and rs10965064 was the best model for predicting SONFH occurrence (p < 0.0001). CONCLUSION: The study indicated that rs10965059 could be involved in SONFH occurrence in the Chinese Han population, which might provide clues for investigating the role of MIR31HG in the pathogenesis of SONFH.

Implementation of Quantum Level Addressability and Geometric Phase Manipulation in Aligned Endohedral Fullerene Qudits.

Endohedral nitrogen fullerenes have been proposed as building blocks for quantum information processing due to their long spin coherence time. However, addressability of the individual electron spin levels in such a multiplet system of 4 S3/2 has never been achieved because of the molecular isotropy and transition degeneracy among the Zeeman levels. Herein, by molecular engineering, we lifted the degeneracy by zero-field splitting effects and made the multiple transitions addressable by a liquid-crystal-assisted method. The endohedral nitrogen fullerene derivatives with rigid addends of spiro structure and large aspect ratios of regioselective bis-addition improve the ordering of the spin ensemble. These samples empower endohedral-fullerene-based qudits, in which the transitions between the 4 electron spin levels were respectively addressed and coherently manipulated. The quantum geometric phase manipulation, which has long been proposed for the advantages in error tolerance and gating speed, was implemented in a pure electron spin system using molecules for the first time.

Multiprocessing Quantum Computing through Hyperfine Couplings in Endohedral Fullerene Derivatives.

Magnetic molecules have shown great potential in quantum information processing due to the chemical tunablity of their quantum behaviors. Chemical derivatives of endohedral nitrogen fullerenes with long coherence time and rich energy levels were synthesized and studied to demonstrate the ability of multiprocessing in quantum information using electron magnetic resonance. After initialization of the 12-levelled spin system, subgroups of spin energy levels coursed by the hyperfine couplings can be selectively manipulated. The cooperatively combining of the parallel calculations enabled quantum error correction, increasing the correct rate by up to 17.82 %. Also, different subgroups of transitions divided by hyperfine coupling can be treated as independent qubits, and multi-task quantum computing were realized by performing Z-gate and X-gate simultaneously, which accelerates the overall gating speed.

Chitooligosaccharide inhibits RANKL-induced osteoclastogenesis and ligation-induced periodontitis by suppressing MAPK/ c-fos/NFATC1 signaling.

Considering the high rate of osteoclast-related diseases worldwide, research targeting osteoclast formation/function is crucial. In vitro, we demonstrated that chitooligosaccharide (CS) dramatically inhibited osteoclastogenesis as well as osteoclast function dose-dependently. CS suppressed osteoclast-specific genes expression during osteoclastogenesis. Furthermore, we found that CS attenuated receptor activator of nuclear factor kappa B ligand (RANKL)-mediated mitogen-activated protein kinase (MAPK) pathway involving p38, erk1/2, and jnk, leading to the reduced expression of c-fos and nuclear factor of activated T cells c1 (NFATc1) during osteoclast differentiation. In vivo, we found CS protected rats from periodontitis-induced alveolar bone loss by micro-computerized tomography and histological analysis. Overall, CS inhibited RANKL-induced osteoclastogenesis and ligature-induced rat periodontitis model, probably by suppressing the MAPK/c-fos/NFATc1 signaling pathway. Therefore, CS may be a safe and promising treatment for osteoclast-related diseases.

2D Sandwiched Nano Heterostructures Endow MoSe2 /TiO2- x /Graphene with High Rate and Durability for Sodium Ion Capacitor and Its Solid Electrolyte Interphase Dependent Sodiation/Desodiation Mechanism.

Nano heterostructures relying on their versatile construction and the breadth of combined functionality have shown great potential in energy storage fields. Herein, 2D sandwiched MoSe2 /TiO2- x /graphene nano heterostructures are designed by integrating structural and functional effects of each component, aiming to address the rate capability and cyclic stability of MoSe2 for sodium ion capacitors (SICs). These 2D nano heterostructures based on graphene platform can facilitate the interfacial electron transport, giving rise to fast reaction kinetics. Meanwhile, the 2D open structure induces a large extent of surface capacitive contribution, eventually leading to a high rate capability (415.2 mAh g-1 @ 5 A g-1 ). An ultrathin oxygen deficient TiO2- x layer sandwiched in these nano heterostructures provides a strong chemical-anchoring regarding the products generated during the sodiation/desodiation process, securing the entire cyclic stability. The associated sodiation/desodiation mechanism is revealed by operando and ex situ characterizations, which exhibits a strong solid electrolyte interphase (SEI) dependence. The simulations verify the dependent sodiation products and enhanced heterostructural chemical-anchoring. Assembled SICs based on these nano heterostructures anode exhibit high initial Coulombic efficiency, energy/power densities, and long cycle life, shedding new light on the design of nano heterostructure electrodes for high performance energy storage application.

Nirogacestat suppresses RANKL-Induced osteoclast formation in vitro and attenuates LPS-Induced bone resorption in vivo.

Bone resorption, initiated by osteoclasts (OCs), plays an essential role in bone homeostasis. The abnormalities of bone resorption may induce a series of diseases, including osteoarthritis, osteoporosis and aseptic peri-implant loosening. Nirogacestat (PF-03084014, PF), a novel gamma-secretase inhibitor, has been used in phase II clinical trial for treatment of desmoid tumor. However, whether it has the therapeutic effect on abnormal bone resorption remains to be evaluated. In this study, we investigated the role of PF in the regulation of receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclastogenesis in vitro, and the lipopolysaccharide (LPS)-induced bone resorption in vivo. It was found that PF could suppress the formation of osteoclasts from bone marrow macrophages (BMMs) without causing cytotoxicity, inhibit bone resorption and downregulate the mRNA level of osteoclast-specific markers, including calcitonin receptor (CTR), tartrate resistant acid phosphatase (TRAP), cathepsin K (CTSK), dendritic cell-specific transmembrane protein (Dc-stamp), Atp6v0d2 (V-ATPase d2) and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). Furthermore, Notch2 signaling, as well as RANKL-induced AKT signaling was significantly inhibited in BMMs. Consistent with in vitro observation, we found that PF greatly ameliorated LPS-induced bone resorption. Taken together, our study demonstrated that PF has a great potential to be used in management of osteolytic diseases.

AZD8835 inhibits osteoclastogenesis and periodontitis-induced alveolar bone loss in rats.

Chronic periodontitis (CP) is one of the most common oral diseases, which is characterized by the loss of connective tissue and alveolar bone in adults. AZD8835, a novel dual phosphoinositide-3-kinase (PI3K) inhibitor, is currently in phase 1 clinical evaluation to treat breast cancer. However, whether AZD8835 has any effect on teeth and alveolar bone health remains unclear. In the current study, we aimed to investigate the potential effect of AZD8835 in treating CP in vitro and in vivo. We found that AZD8835 could inhibit osteoclast differentiation, bone resorption, and downregulate the expression of osteoclast marker genes, such as tartrate-resistant acid phosphatase (Trap), cathepsin K (Ctsk), V-ATPase d2 (Atp6v0d2), and calcitonin receptor (Ctr). In addition, AZD8835 suppressed osteoclastogenesis by inhibiting receptor activator of nuclear factor kappa B ligand (RANKL)-induced PI3K/protein kinase B (AKT), extracellular signal-regulated kinase, and nuclear factor-κB signaling in BMMs. In vivo, AZD8835 greatly ameliorated alveolar bone (ABL) loss in rats with CP. Meanwhile, histological examination showed fewer osteoclasts in the treatment group. In conclusion, these results indicated that AZD8835 is a promising agent to reduce ABL in CP.

LY411575, a potent γ-secretase inhibitor, suppresses osteoclastogenesis in vitro and LPS-induced calvarial osteolysis in vivo.

A series of osteolytic bone diseases are usually related to excessive bone resorption and osteoclast formation. Thus, agents or drugs which can target osteoclast development and attenuate bone loss are potentially considerable in preventing and treating of bone lytic diseases. In recent years, many studies have reported that Notch signaling has substantial impacts on the process of osteoclast differentiation, maturation, and bone destruction. In the present study, we showed that LY411575, a γ-secretase inhibitor, could potently suppress osteoclast differentiation, osteoclast-specific gene expression, and bone resorption via suppressing Notch/HES1/MAPK (ERK and p38)/Akt-mediated NFATc1 induction in vitro. Consistent with in vitro results, LY411575 exhibited protective effects in lipopolysaccharides-induced calvarial bone destruction in vivo. Collectively, these results indicate that LY411575 may have therapeutic potential in the treatment of osteoclast-mediated osteolytic bone diseases.

Single-Crystal Study of a Low Spin Co(II) Molecular Qubit: Observation of Anisotropic Rabi Cycles.

A mononuclear low spin ( S = 1/2) Co(II) molecule crystallized in a 4-fold symmetry is fully investigated by CW and pulsed EPR on a single crystal sample. The quantum phase memory time of the molecule around 1 µs at 5 K is direction-independent, while the Rabi oscillation frequency is anisotropic. The spin Hamiltonian analyses reveal that the anisotropic Landé factor and hyperfine tensor do not influence the anisotropy apparently when the microwave magnetic field is applied along a certain direction. It is considered that the possibly involved nuclear spin forbidden transitions may be responsible for the small distinction of Rabi frequencies in two directions.

Delta-like 2 negatively regulates chondrogenic differentiation.

Delta-like 2 (Dlk2), a glycoprotein highly homologous to Dlk1, belongs to the Notch/Delta/Serrata family. Dlk2 has been shown to be an important regulator of adipogenesis; however, its role in other cellular differentiation processes is still unknown. Therefore, in this study, we aimed to determine the role of Dlk2 in chondrogenic differentiation. We found that Dlk2 overexpression promoted the growth of ATDC5 cells but inhibited insulin-induced ATDC5 chondrogenic differentiation, as supported by the reduction in cartilage matrix formation and gene expression of aggrecan (acan), collagentype II (col2a1) and X (col10a1). In contrast, Dlk2 silencing inhibited the proliferation of ATDC5 cells but enhanced their chondrogenic differentiation. We then evaluated the roles of mitogen-activated protein kinases (MAPKs), which are activated by insulin during the chondrogenesis of ATDC5 cells. Overexpression of Dlk2 protein strongly promoted the activation of p38, but not extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK). Moreover, as expected, Dlk2 silencing inhibited the activation of p38, but had no effect on the ERK1/2 and JNK pathways. Finally, we also detected the expression of Dlk2 in mouse epiphyseal cartilage during embryo development. The expression of the Dlk2 protein in the limb bud could be detected at embryonic day 11.5; additionally, it was found to decrease in the superficial zones, but remained unchanged in the deep/hypertrophic zones. In conclusion, our results suggested that Dlk2 acted as an important regulator of chondrogenesis through the p38 pathway. These findings may lead to strategies for the treatment of cartilage-related diseases such as osteoarthritis.

Comparative Efficacy of Alendronate upon Vertebral Bone Mineral Density and Fracture Rates in East Asians Versus Non-East Asians with Postmenopausal Osteoporosis: A Systematic Review and Meta-Analysis.

Bisphosphonates, such as alendronate, have become the most widely used and effective anti-resorptive therapy for postmenopausal osteoporosis. Previous genetic studies suggest that ethnicity may drive differing responses to bisphosphonate therapy in East Asians and non-East Asians. Therefore, the aim of this study was to comparatively evaluate the efficacy of alendronate upon lumbar spinal BMD and vertebral fracture rates in East Asians and non-East Asians with postmenopausal osteoporosis. MEDLINE, EMBASE, and Cochrane CENTRAL were searched for relevant randomized controlled trials (RCTs) comparing the efficacy of alendronate versus placebo (or calcium/mineral and/or Vitamin D or hormone replacement therapy) in primary postmenopausal osteoporotic women. We calculated the weighted mean differences (WMDs) for lumbar spinal BMD and the risk ratios (RRs) for vertebral fracture risk along with their respective 95% confidence intervals (CIs). From an initial set of 445 non-duplicate records, 13 full-text articles were finally included in this meta-analysis consisting of four East Asian RCTs and nine non-East Asian RCTs. Alendronate therapy displayed significant effects in improving lumbar spinal BMD in both East Asians [WMD (95% CI)=5.30 (0.32-10.29), p=0.037] and non-East Asians [WMD (95% CI)=5.73 (3.61-7.85), p=0.000]. Alendronate therapy did not display significant effects upon vertebral fracture risk in East Asians [RR (95% CI)=0.41 (0.06-2.73), p=0.358] but did display a significant effect upon lowering vertebral fracture risk in non-East Asians [RR (95% CI)=0.55 (0.42-0.72), p=0.000]. These findings suggest that ethnicity may affect the efficacy of bisphosphonate therapy in postmenopausal osteoporotic women.

Three-dimensional imaging of distribution of refractive index by parallel phase-shifting digital holography using Abel inversion.

Although digital holography is a powerful technique obtaining a phase image of a transparent object, the image reconstructed by the technique merely expresses phase distribution of the light wave after transmitting through the object. Phase variation of inside of the object is difficult to be obtained. Then, we applied Abel inversion method to the high-speed phase image of a dynamic transparent object assumed axially symmetric. The phase is accurately recorded by phase-shifting method. We experimentally recorded transparent dynamic gas flow, assumed axially symmetric along the direction in which gas flowed, at 3,000 frame/s and reconstructed motion picture of 3D distribution of the refractive index of the gas from the high-speed phase motion picture obtained by parallel phase-shifting digital holography.

Two Magnetic Switching Complexes Based on the Fe(II) Ion.

Two neutral mononuclear iron(II) complexes with different spin-crossover (SCO) properties, Fe(L1)2(SCN)2 (1) and Fe(L2)2(SCN)2 (2) (L1 = 2-(thiophen-3-yl)-1H-imidazo[4,5-f][1,10]phenanthroline and L2 = 2-(thiophen-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline), were solvothermally synthesized. With the different substituted position in 1,10-phenanthroline derivatives, 1 exhibits gradual SCO around room temperature with T1/2 = 280 K, while 2 displays abrupt SCO with 10 K hysteresis at T1/2↓ = 210 K and T1/2↑ = 220 K.

Calibration and 3D reconstruction of underwater objects with non-single-view projection model by structured light stereo imaging.

Establishing the projection model of imaging systems is critical in 3D reconstruction of object shapes from multiple 2D views. When deployed underwater, these are enclosed in waterproof housings with transparent glass ports that generate nonlinear refractions of optical rays at interfaces, leading to invalidation of the commonly assumed single-viewpoint (SVP) model. In this paper, we propose a non-SVP ray tracing model for the calibration of a projector-camera system, employed for 3D reconstruction based on the structured light paradigm. The projector utilizes dot patterns, having established that the contrast loss is less severe than for traditional stripe patterns in highly turbid waters. Experimental results are presented to assess the achieved calibrating accuracy.

RGB-D SLAM Based on Extended Bundle Adjustment with 2D and 3D Information.

In the study of SLAM problem using an RGB-D camera, depth information and visual information as two types of primary measurement data are rarely tightly coupled during refinement of camera pose estimation. In this paper, a new method of RGB-D camera SLAM is proposed based on extended bundle adjustment with integrated 2D and 3D information on the basis of a new projection model. First, the geometric relationship between the image plane coordinates and the depth values is constructed through RGB-D camera calibration. Then, 2D and 3D feature points are automatically extracted and matched between consecutive frames to build a continuous image network. Finally, extended bundle adjustment based on the new projection model, which takes both image and depth measurements into consideration, is applied to the image network for high-precision pose estimation. Field experiments show that the proposed method has a notably better performance than the traditional method, and the experimental results demonstrate the effectiveness of the proposed method in improving localization accuracy.

Precise calibration of binocular vision system used for vision measurement.

Binocular vision calibration is of great importance in 3D machine vision measurement. With respect to binocular vision calibration, the nonlinear optimization technique is a crucial step to improve the accuracy. The existing optimization methods mostly aim at minimizing the sum of reprojection errors for two cameras based on respective 2D image pixels coordinate. However, the subsequent measurement process is conducted in 3D coordinate system which is not consistent with the optimization coordinate system. Moreover, the error criterion with respect to optimization and measurement is different. The equal pixel distance error in 2D image plane leads to diverse 3D metric distance error at different position before the camera. To address these issues, we propose a precise calibration method for binocular vision system which is devoted to minimizing the metric distance error between the reconstructed point through optimal triangulation and the ground truth in 3D measurement coordinate system. In addition, the inherent epipolar constraint and constant distance constraint are combined to enhance the optimization process. To evaluate the performance of the proposed method, both simulative and real experiments have been carried out and the results show that the proposed method is reliable and efficient to improve measurement accuracy compared with conventional method.