Inhibition of circDGKZ ameliorates myocardial ischemia/reperfusion injury by targeting miR-345-5p/TLR4.

Aims: This study aims to explore the molecular mechanism of circular RNAs' (circRNAs) potential involvement in myocardial ischaemia-reperfusion injury (MIRI).

Methods And Results: Differently expressed genes in myocardial infarction (MI) were identified by screening the GEO database. Serum was collected from MI patients and healthy volunteers (n = 5 for each group).

A Novel Method for Targeted Identification of Essential Proteins by Integrating Chemical Reaction Optimization and Naive Bayes Model.

Targeted identification of essential proteins is of great significance for species identification, drug manufacturing, and disease treatment. It is a challenge to analyze the binding mechanism between essential proteins and improve the identification speed while ensuring the accuracy of the identification. This paper proposes a novel method called EPCRO for identifying essential proteins, which incorporates the chemical reaction optimization (CRO) algorithm and the naive Bayes model to effectively detect essential proteins.

Facile and Controllable Synthesis of CuS@Ni-Co Layered Double Hydroxide Nanocages for Hybrid Supercapacitors.

The synthesis of battery-type electrode materials with hollow nanostructures for high-performance hybrid supercapacitors (HSCs) remains challenging. In this study, hollow CuS@Ni-Co layered double hydroxide (CuS-LDH) composites with distinguished compositions and structures are successfully synthesized by co-precipitation and the subsequent etching/ion-exchange reaction. CuS-LDH-10 with uniformly dispersed CuS prepared with the addition of 10 mg of CuS shows a unique hollow polyhedral structure constituted by loose nanosphere units, and these nanospheres are composed of interlaced fine nanosheets.

Interaction in Li@Fullerenes and Li@Fullerenes: First Principle Insights to Li-Based Endohedral Fullerenes.

This work reveals first principle results of the endohedral fullerenes made from neutral or charged single atomic lithium (Li or Li) encapsulated in fullerenes with various cage sizes. According to the calculated binding energies, it is found that the encapsulation of a single lithium atom is energetically more favorable than that of lithium cation. Lithium, in both atomic and cationic forms, exhibits a clear tendency to depart from the center in large cages.

Discovery of ITX 4520: a highly potent orally bioavailable hepatitis C virus entry inhibitor.

The manuscript reports an identification of a highly potent, orally bioavailable hepatitis C virus entry inhibitor through optimization of a previously reported class of molecules (1) that were not stable in the rat plasma. Compound 39 (ITX 4520) exhibited an excellent PK profile in both rats and dogs with good oral exposure, half-life and oral bioavailability. The compound is also well-tolerated in the preliminary in vivo toxicity studies and has been selected as a pre-clinical candidate for our HCV clinical pipeline.

Semaphorin3A regulates neuronal polarization by suppressing axon formation and promoting dendrite growth.

Semaphorin 3A (Sema3A) is a secreted factor known to guide axon/dendrite growth and neuronal migration. We found that it also acts as a polarizing factor for axon/dendrite development in cultured hippocampal neurons. Exposure of the undifferentiated neurite to localized Sema3A suppressed its differentiation into axon and promoted dendrite formation, resulting in axon formation away from the Sema3A source, and bath application of Sema3A to polarized neurons promoted dendrite growth but suppressed axon growth.

Phosphorylation of E3 ligase Smurf1 switches its substrate preference in support of axon development.

Ubiquitin E3 ligases serve for ubiquitination of specific substrates, and its ligase efficacy is regulated by interacting proteins or substrate modifications. Whether and how the ligases themselves are modified by cellular signaling is unclear. Here we report that protein kinase A (PKA)-dependent phosphorylation of Smad Ubiquitin Regulatory Factor 1 (Smurf1) can switch its substrate preference between two proteins of opposing actions on axon development.

Local and long-range reciprocal regulation of cAMP and cGMP in axon/dendrite formation.

Cytosolic cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) often mediate antagonistic cellular actions of extracellular factors, from the regulation of ion channels to cell volume control and axon guidance. We found that localized cAMP and cGMP activities in undifferentiated neurites of cultured hippocampal neurons promote and suppress axon formation, respectively, and exert opposite effects on dendrite formation. Fluorescence resonance energy transfer imaging showed that alterations of the amount of cAMP resulted in opposite changes in the amount of cGMP, and vice versa, through the activation of specific phosphodiesterases and protein kinases.

Differential activity-dependent secretion of brain-derived neurotrophic factor from axon and dendrite.

Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival and differentiation during development and for synaptic function and plasticity in the mature brain. BDNF-containing vesicles are widely distributed and bidirectionally transported in neurons, and secreted BDNF can act on both presynaptic and postsynaptic cells. Activity-dependent BDNF secretion from neuronal cultures has been reported, but it remains unknown where the primary site of BDNF secretion is and whether neuronal activity can trigger BDNF secretion from axons and dendrites with equal efficacy.

Axon initiation and growth cone turning on bound protein gradients.

Extracellular gradients of secreted guidance factors are known to guide axon pathfinding and neuronal migration. These factors are likely to bind to cell surfaces or extracellular matrix, but whether and how they may act in bound gradients remains mostly unclear. In this study, we have developed a new technique for rapid production of stable microscopic gradients of substrate-bound proteins by covalent bonding of the proteins with an epoxy-coated glass substrate while they are diffusing in an agarose gel.

Anti-inflammatory effects of LJP 1586 [Z-3-fluoro-2-(4-methoxybenzyl)allylamine hydrochloride], an amine-based inhibitor of semicarbazide-sensitive amine oxidase activity.

Semicarbazide-sensitive amine oxidase (SSAO, amine oxidase, copper-containing 3, and vascular adhesion protein-1) is a copper-containing enzyme that catalyzes the oxidative deamination of primary amines to an aldehyde, ammonia, and hydrogen peroxide. SSAO is also involved in leukocyte migration to sites of inflammation, and the enzymatic activity of SSAO is essential to this role. Thus, inhibition of SSAO enzyme activity represents a target for the development of small molecule anti-inflammatory compounds.

Bioactive nanofibers: synergistic effects of nanotopography and chemical signaling on cell guidance.

Biodegradable nanofibers have tremendous potential for tissue repair. However, the combined effects of nanofiber organization and immobilized bioactive factors on cell guidance are not well understood. In this study, we developed aligned and bioactive nanofibrous scaffolds by immobilizing extracellular matrix protein and growth factor onto nanofibers, which simulated the physical and biochemical properties of native matrix fibrils.

Rapid learning in cortical coding of visual scenes.

Experience-dependent plasticity in adult visual cortex is believed to have important roles in visual coding and perceptual learning. Here we show that repeated stimulation with movies of natural scenes induces a rapid improvement in response reliability in cat visual cortex, whereas stimulation with white noise or flashed bar stimuli does not. The improved reliability can be accounted for by a selective increase in spiking evoked by preferred stimuli, and the magnitude of improvement depends on the sparseness of the response.

Design, synthesis, and biological evaluation of semicarbazide-sensitive amine oxidase (SSAO) inhibitors with anti-inflammatory activity.

In an attempt to examine the effect of inhibition of semicarbazide-sensitive amine oxidase (SSAO; EC 1.4.3.

Anti-inflammatory effects of inhibiting the amine oxidase activity of semicarbazide-sensitive amine oxidase.

Human semicarbazide-sensitive amine oxidase (SSAO) or vascular adhesion protein-1 (VAP-1) is a copper-containing amine oxidase (AOC3, EC 1.4.3.

Spike timing-dependent synaptic plasticity in visual cortex: a modeling study.

Recent studies show that synaptic modification depends critically on the relative spike timing of pre- and postsynaptic neurons. Here we explore the functional implications of spike timing-dependent synaptic plasticity in the visual cortex using a model circuit with modifiable intracortical excitatory connections. First we simulated the experiments using two-point stimuli, in which two visual stimuli in a topographically represented feature space were repeatedly presented in quick succession, and found that tuning of the cortical neurons was modified in a manner similar to that observed experimentally.

Asymmetry in visual cortical circuits underlying motion-induced perceptual mislocalization.

Motion signals in the visual field can cause strong biases in the perceived positions of stationary objects. Local motion signal within an object induces a shift in the perceived object position in the direction of motion, whereas adaptation to motion stimuli causes a perceptual shift in the opposite direction. The neural mechanisms underlying these illusions are poorly understood.

Temporal specificity in the cortical plasticity of visual space representation.

The circuitry and function of mammalian visual cortex are shaped by patterns of visual stimuli, a plasticity likely mediated by synaptic modifications. In the adult cat, asynchronous visual stimuli in two adjacent retinal regions controlled the relative spike timing of two groups of cortical neurons with high precision. This asynchronous pairing induced rapid modifications of intracortical connections and shifts in receptive fields.