Inhibition of human carboxylesterases by magnolol : Kinetic analyses and mechanism

Magnolol, the most abundant bioactive constituent of the Chinese herb Magnolia officinalis, has been found with multiple biological activities, including anti-oxidative, anti-inflammatory and enzyme-regulatory activities. In this study, the inhibitory effects and inhibition mechanism of magnolol on human carboxylesterases (hCEs), the key enzymes responsible for the hydrolytic metabolism of a variety of endogenous esters as well as ester-bearing drugs, have been well-investigated. The results demonstrate that magnolol strongly inhibits hCE1-mediated hydrolysis of various substrates, whereas the inhibition of hCE2 by magnolol is substrate-dependent, ranging from strong to moderate. Inhibition of intracellular hCE1 and hCE2 by magnolol was also investigated in living HepG2 cells, and the results showed that magnolol could strongly inhibit intracellular hCE1, while the inhibition of intracellular hCE2 was weak. Inhibition kinetic analyses and docking simulations revealed that magnolol inhibited both hCE1 and hCE2 in a mixed manner, which could be partially attributed to its binding at two distinct ligand-binding sites in each carboxylesterase, including the catalytic cavity and the regulatory domain. In addition, the potential risk of the metabolic interactions of magnolol via hCE1 inhibition was predicted on the basis of a series of available pharmacokinetic data and the inhibition constants. All these findings are very helpful in deciphering the metabolic interactions between magnolol and hCEs, and also very useful for avoiding deleterious interactions via inhibition of hCEs.Peer reviewe

Non-covalent surface modification of boron nitride nanotubes for enhanced catalysis

Boron nitride nanotubes were functionalized by microperoxidase-11 in aqueous media, showing improved catalytic performance due to a strong electron coupling 10 between the active centre of microperoxidase-11 and boron nitride nanotubes. One main application challenge of enzymes as biocatalysts is molecular aggregation in the aqueous solution. This issue is addressed by immobilization of enzymes on solid supports which 15 can enhance enzyme stability and facilitate separation, and recovery for reuse while maintaining catalytic activity and selectivity. The protein-nanoparticle interactions play a key role in bio-nanotechnology and emerge with the development of nanoparticle-protein “corona”. Bio-molecular coronas provide a 20 unique biological identity of nanosized materials.1, 2 As a structural analogue to carbon nanotubes (CNTs), Boron nitride nanotubes have boron and nitrogen atoms distributed equally in hexagonal rings and exhibit excellent mechanical strength, unique physical properties, and chemical stability at high-temperatures. 25 The chemical inertness of BN materials suits to work in hazardous environments, making them an optimal candidate in practical applications in biological and medical field.3,

Ultraflexible and Energy‐Efficient Artificial Synapses Based on Molecular/Atomic Layer Deposited Organic–Inorganic Hybrid Thin Films

Abstract Flexible artificial synapses, a conjunctive product of brain‐inspired neuromorphic computing and wearable electronics, arouse enormous interest in highly connected and energy‐efficient neural networks. The organic–inorganic hybrid materials hold great potential in flexible devices due to versatile properties. Here, an organic–inorganic hybrid synaptic device consisting of 2 nm Al2O3 and 22 nm Al‐based hydroquinone (Al‐HQ) sandwiched between Pt and poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) electrodes is prepared on highly flexible cellophane by molecular/atomic layer deposition (MLD/ALD). The vertically integrated Pt/Al2O3/Al‐HQ/PEDOT:PSS device exhibits reliable resistive switching with an ON/OFF ratio greater than 103. Several important bio‐synaptic functions, such as long‐term potentiation, long‐term depression, paired‐pulse facilitation, and spike‐time‐dependent plasticity, are realized in this device with the extremely low energy consumption of ≈25.2 fJ per reset operation, which is ascribed to the unique electron trapping/detrapping and tunneling mechanism. Remarkably, the excellent flexibility and robustness of this hybrid synaptic device is confirmed under the minimum curvature radius of ≈0.7 mm after 104 bending cycles. A pattern recognition computation based on these hybrid synapse devices shows a 90.2% learning accuracy. This research paves a way for the MLD/ALD‐derived organic–inorganic‐hybrid‐based artificial synapse applications in flexible energy‐efficient neuron network systems toward system‐on‐plastics

The accuracy of a method for printing three-dimensional spinal models.

To study the morphology of the human spine and new spinal fixation methods, scientists require cadaveric specimens, which are dependent on donation. However, in most countries, the number of people willing to donate their body is low. A 3D printed model could be an alternative method for morphology research, but the accuracy of the morphology of a 3D printed model has not been determined.Forty-five computed tomography (CT) scans of cervical, thoracic and lumbar spines were obtained, and 44 parameters of the cervical spine, 120 parameters of the thoracic spine, and 50 parameters of the lumbar spine were measured. The CT scan data in DICOM format were imported into Mimics software v10.01 for 3D reconstruction, and the data were saved in .STL format and imported to Cura software. After a 3D digital model was formed, it was saved in Gcode format and exported to a 3D printer for printing. After the 3D printed models were obtained, the above-referenced parameters were measured again.Paired t-tests were used to determine the significance, set to P<0.05, of all parameter data from the radiographic images and 3D printed models. Furthermore, 88.6% of all parameters of the cervical spine, 90% of all parameters of the thoracic spine, and 94% of all parameters of the lumbar spine had Intraclass Correlation Coefficient (ICC) values >0.800. The other ICC values were <0.800 and >0.600; none were <0.600.In this study, we provide a protocol for printing accurate 3D spinal models for surgeons and researchers. The resulting 3D printed model is inexpensive and easily obtained for spinal fixation research

The parameters of L1–L5 and comparison of data from radiographic images and 3D-printed models.

<p><b>Note</b>: <b>WVD</b>: Width of vertebral body; <b>APDVD</b>: Anteroposterior diameter of vertebral body; <b>LHVD</b>: Left height of vertebral body; <b>RHVD</b>: Right height of vertebral body; <b>WVC</b>: Width of vertebral canal; <b>APDVC</b>: Anteroposterior diameter of vertebral canal; <b>WRP</b>: Width of right pedicle; <b>HRP</b>: Height of right pedicle; <b>WLP</b>: Width of left pedicle; <b>HLP</b>: Height of left pedicle.</p><p>The parameters of L1–L5 and comparison of data from radiographic images and 3D-printed models.</p