Therapeutic efficacy of dexmedetomidine on chronic obstructive pulmonary disease via downregulating lncRNA PACER.

OBJECTIVE: The aim of the study was to clarify the therapeutic mechanism of Dexmedetomidine (DEX) on the chronic obstructive pulmonary disease (COPD) and its regulatory effect on long non-coding RNA (lncRNA) PACER. PATIENTS AND METHODS: Serum level of PACER in COPD patients was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic potential of PACER in COPD was assessed by plotting ROC curves. The in vivo COPD model was generated in rats by cigarette smoking exposure. Primary rat alveolar epithelial cells were isolated, purified and cultured. After overexpression of PACER in primary rat alveolar epithelial cells, proliferative and migratory abilities were assessed by cell counting kit-8 (CCK-8) and transwell assay, respectively. Subsequently, we detected changes in PACER expression, viability and migratory potentials in primary rat alveolar epithelial cells harvested from control rats, and those harvested from COPD rats and induced with either DEX or not. Rescue experiments were conducted to uncover the involvement of PP2A in PACER-regulated cell phenotypes. RESULTS: PACER was upregulated in serum of COPD patients, which was a potential biomarker for diagnosing COPD. Overexpression of PACER in primary rat alveolar epithelial cells enhanced proliferative and migratory abilities. Compared with primary rat alveolar epithelial cells harvested from control rats, proliferative and migratory abilities were stronger in those harvested from COPD rats and induced with either DEX or not. Notably, DEX induction decreased PACER expression, and proliferative and migratory abilities in primary rat alveolar epithelial cells harvested from COPD rats. Overexpression of PP2A could partially abolish the promotive effects of PACER on proliferative and migratory abilities in DEX-induced primary rat alveolar epithelial cells harvested from COPD rats. CONCLUSIONS: PACER drives the proliferative and migratory abilities of alveolar epithelial cells through activating PP2A. Dexmedetomidine is conducive to COPD treatment by downregulating PACER.

On the fracture mechanisms of nacre: Effects of structural orientation.

The nacre of mollusk shells is distinguished by an exceptional mechanical efficiency which is derived essentially from its lamellar structure and frequently acts as a source of inspiration for the development of biomimetic materials. The structure and mechanical properties of nacre have been intensively investigated with a special focus on its toughening strategies; nevertheless, the fracture mechanisms, more specifically the critical stress/strain conditions for the failure of nacre, and the effects of structural orientation and hydration state remain largely unexplored. Here uniaxial compression tests were performed on nacre of both dry and hydrated states with different off-axis angles, i.e., the inclination of loading axis with respect to the lamellar structure, ranging from 0° to 90°. The mechanical properties and fracture characteristics of nacre and their dependences on the structural orientation and hydration state were elucidated in terms of mechanics behind failure. Quantitative relationships were established between the mechanical properties and off-axis angle based on different failure criteria. The competition between the fracture modes of fragmentation and shearing was quantified by comparing their respective driving force and resistance on the interfacial plane. This study may aid the understanding on the mechanical behavior of nacre and nacre-inspired synthetic materials and promote a better replication of the underlying design principles of nacre in man-made systems.

Giant panda׳s tooth enamel: Structure, mechanical behavior and toughening mechanisms under indentation.

The giant panda׳s teeth possess remarkable load-bearing capacity and damage resistance for masticating bamboos. In this study, the hierarchical structure and mechanical behavior of the giant panda׳s tooth enamel were investigated under indentation. The effects of loading orientation and location on mechanical properties of the enamel were clarified and the evolution of damage in the enamel under increasing load evaluated. The nature of the damage, both at and beneath the indentation surfaces, and the underlying toughening mechanisms were explored. Indentation cracks invariably were seen to propagate along the internal interfaces, specifically the sheaths between enamel rods, and multiple extrinsic toughening mechanisms, e.g., crack deflection/twisting and uncracked-ligament bridging, were active to shield the tips of cracks from the applied stress. The giant panda׳s tooth enamel is analogous to human enamel in its mechanical properties, yet it has superior hardness and Young׳s modulus but inferior toughness as compared to the bamboo that pandas primarily feed on, highlighting the critical roles of the integration of underlying tissues in the entire tooth and the highly hydrated state of bamboo foods. Our objective is that this study can aid the understanding of the structure-mechanical property relations in the tooth enamel of mammals and further provide some insight on the food habits of the giant pandas.

Mechanical behavior of mother-of-pearl and pearl with flat and spherical laminations.

Laminated structure reduces the common inverse relationship of strength and toughness in many biological materials. Here the mechanical behavior of pearl and nacre with spherical and flat laminations was investigated and compared with the geological aragonite counterpart. The biological ceramics demonstrate higher strength, better reliability, and improved damage resistance owing to their laminated arrangement. Kinking and delamination occur in pearl to resist damage in addition to the crack-tip shielding mechanisms as in nacre, such as crack deflection, bridging, and platelet pull-out. The fracture mechanisms were interpreted in terms of the stress state using finite element simulation. This study may help clarify the compressive mechanics of laminated sphere between platens and advance the understanding on the mechanical behavior of biological and bio-inspired laminated materials.

Water-assisted self-healing and property recovery in a natural dermal armor of pangolin scales.

Self-healing capacity, of which the inspiration comes from biological systems, is significant for restoring the mechanical properties of materials by autonomically repairing damages. Clarifying the naturally occurring self-healing behaviors and mechanisms may provide valuable inspiration for designing synthetic self-healing materials. In this study, water-assisted self-healing behavior was revealed in a natural dermal armor of pangolin scales. The indentation damages which imitate the injury caused by predatory attack can be continuously mitigated through hydration. The healing kinetics was characterized according to the variations of indentation crater dimension and quantitatively described in terms of the viscoelastic behavior of biopolymer. The mechanical properties of original, damaged, and recovered scales in both dry and wet states were systematically evaluated by three-point bending and compared through statistical analysis. The hydration effects and mechanisms were explored by examining the dynamic mechanical properties and thermal behaviors. The promoted self-healing process can be attributed to the improved flexibility of macromolecules in the biopolymer. This study may stimulate useful self-healing strategies in bio-inspired design and aid in developing high-performance synthetic self-healing materials.

Structure and mechanical behaviors of protective armored pangolin scales and effects of hydration and orientation.

As natural flexible dermal armor, pangolin scales provide effective protection against predatory threats and possess other notable properties such as anti-adhesion and wear-resistance. In this study, the structure, mechanical properties, deformation and damage behaviors of pangolin scales were systematically investigated with the effects of hydration and orientation evaluated. The scales are divided into three macro-layers constituted by overlapping keratin tiles with distinct lamellar arrangements which are further composed of lower-ordered lamellae. Both hardness and strength are significantly decreased by hydration; while the plasticity is markedly improved concomitantly, and as such, the mechanical damages are mitigated. The tensile strength invariably approximates to one third of hardness in value. The tensile deformation is dominated by lamellae stretching and pulling out under wet condition, which is distinct from the trans-lamellar fracture in dry samples. The compressive behaviors are featured by pronounced plasticity in both dry and wet scales; and notable strain-hardening capacity is introduced by hydration, especially along the thickness direction wherein kinking occurs. Inter-lamellar cracking is effectively alleviated in wet samples compared with the dry ones and both of them deform by macroscopic buckling. This study may help stimulate possible inspiration for the design of high-performance synthetic armor materials by mimicking pangolin scales.

Second renormalization of tensor-network states.

We propose a second renormalization group method to handle the tensor-network states or models. This method dramatically reduces the truncation error of the tensor renormalization group. It allows physical quantities of classical tensor-network models or tensor-network ground states of quantum systems to be accurately and efficiently determined.

Density matrix renormalization group numerical study of the kagome antiferromagnet.

We numerically study the spin-1/2 antiferromagnetic Heisenberg model on the kagome lattice using the density-matrix renormalization group method. We find that the ground state is a magnetically disordered spin liquid, characterized by an exponential decay of spin-spin correlation function in real space and a magnetic structure factor showing system-size independent peaks at commensurate magnetic wave vectors. We obtain a spin triplet excitation gap DeltaE(S=1)=0.055+/-0.005 by extrapolation based on the large size results, and confirm the presence of gapless singlet excitations. The physical nature of such an exotic spin liquid is also discussed.

Accurate determination of tensor network state of quantum lattice models in two dimensions.

We have proposed a novel numerical method to calculate accurately physical quantities of the ground state using the tensor network wave function in two dimensions. The tensor network wave function is determined by an iterative projection approach which uses the Trotter-Suzuki decomposition formula of quantum operators and the singular value decomposition of matrix. The norm of the wave function and the expectation value of a physical observable are evaluated by a coarse-grain tensor renormalization group approach. Our method allows a tensor network wave function with a high bond degree of freedom (such as D=8) to be handled accurately and efficiently in the thermodynamic limit. For the Heisenberg model on a honeycomb lattice, our results for the ground state energy and the staggered magnetization agree well with those obtained by the quantum Monte Carlo and other approaches.

Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-kappaB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner.

Diterpenoids isolated from Labiatae family herbs have strong antitumor activities with low toxicity. In this study, Eriocalyxin B (EriB), a diterpenoid extracted from Isodon eriocalyx, was tested on human leukemia/lymphoma cells and murine leukemia models. Acute myeloid leukemia cell line Kasumi-1 was most sensitive to EriB. Significant apoptosis was observed, concomitant with Bcl-2/Bcl-XL downregulation, mitochondrial instability and caspase-3 activation. AML1-ETO oncoprotein was degraded in parallel to caspase-3 activation. EriB-mediated apoptosis was associated with NF-kappaB inactivation by preventing NF-kappaB nuclear translocation and inducing IkappaBalpha cleavage, and disturbance of MAPK pathway by downregulating ERK1/2 phosphorylation and activating AP-1. Without affecting normal hematopoietic progenitor cells proliferation, EriB was effective on primary t(8;21) leukemia blasts and caused AML1-ETO degradation. In murine t(8;21) leukemia models, EriB remarkably prolonged the survival time or decreased the xenograft tumor size. Together, EriB might be a potential treatment for t(8;21) leukemia by targeting AML1-ETO oncoprotein and activating apoptosis pathways.

Quantum spin-Hall effect and topologically invariant Chern numbers.

We present a topological description of the quantum spin-Hall effect (QSHE) in a two-dimensional electron system on a honeycomb lattice with both intrinsic and Rashba spin-orbit couplings. We show that the topology of the band insulator can be characterized by a 2 x 2 matrix of first Chern integers. The nontrivial QSHE phase is identified by the nonzero diagonal matrix elements of the Chern number matrix (CNM). A spin Chern number is derived from the CNM, which is conserved in the presence of finite disorder scattering and spin nonconserving Rashba coupling. By using the Laughlin gedanken experiment, we numerically calculate the spin polarization and spin transfer rate of the conducting edge states and determine a phase diagram for the QSHE.

Numerical study of the spin-Hall conductance in the Luttinger model.

We present the first numerical studies of the disorder effect on the recently proposed intrinsic spin-Hall conductance in a three dimensional lattice Luttinger model. The results show that the spin-Hall conductance remains finite in a wide range of disorder strength, with large fluctuations. The disorder-configuration-averaged spin-Hall conductance monotonically decreases with the increase of disorder strength and vanishes before the Anderson localization takes place. The finite-size effect is also discussed.

[Structure-activity-relationship study of the new anticancer drug lycobetaine (AT-1840)].

Lycobetaine (AT-1840), developed by our institute, is a new chemotherapeutic agent with relatively high percentage of remission on the treatment of ovary cancer and stomach cancer; no remarkable changes in blood picture, EKG and GPT, were observed. Early examination of the structure activity relationship of lycobetaine gave the following results: 1. A potential betaine and a methylenedioxy group in this compound may be critical for exhibiting antitumor activity; 2. Fission of the five membered ring of lycobetaine will not affect its antitumor activity. In order to see whether the distance between the phenolic oxygen and quaternary nitrogen affects its antitumor activity, compounds 7a-c, 8a-b were synthesized and screened against tumor in mice bearing EAC Preliminary experimental results showed that among the open ring analogs of lycobetaine, 7a, 7b and 8d possessed marked antitumor activity and 7c did not. The results indicate that changes in the distance of the betaine in lycobetaine obviously influence its antitumor activity.