A new strategy for the treatment of Parkinson's disease: Discovery and bio-evaluation of the first central-targeting tyrosinase inhibitor.

The high level of tyrosinase leads to the generation of neuromelanin, further causing the abnormality of redox-related protein level and mediating the occurrence and development of Parkinson's disease (PD). However, the existing tyrosinase inhibitors are mostly natural product extracts or polyphenolic derivatives, which hindered them from penetrating the blood-brain barrier (BBB). Herein, we obtained a novel tyrosinase inhibitor, 2-06 (tyrosinase: monophenolase IC = 70.

Opportunities and perspectives of small molecular phosphodiesterase inhibitors in neurodegenerative diseases.

Phosphodiesterase (PDE) is a superfamily of enzymes that are responsible for the hydrolysis of two second messengers: cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). PDE inhibition promotes the gene transcription by activating cAMP-response element binding protein (CREB), initiating gene transcription of brain-derived neurotrophic factor (BDNF). The procedure exerts neuroprotective profile, and motor and cognitive improving efficacy.

Targeting glycogen synthase kinase-3β for Alzheimer's disease: Recent advances and future Prospects.

Senile plaques induced by β-amyloid (Aβ) abnormal aggregation and neurofibrillary tangles (NFT) caused by tau hyperphosphorylation are important pathological manifestations of Alzheimer's disease (AD). Glycogen synthase kinase-3 (GSK-3) is a conserved kinase; one member GSK-3β is highly expressed in the AD brain and involved in the formation of NFT. Hence, pharmacologically inhibiting GSK-3β activity and expression is a good approach to treat AD.

Generation and enhancement of the sum sideband under double radiation pressure.

A theoretical scheme to enhance the sum sideband generation (SSG) via double radiation pressure is proposed. In this scheme, both sides of the double-cavity system are driven by red and blue detuned pump lasers and frequency components are generated at the sum sideband through optomechanical nonlinear interaction. The results show that the efficiency of SSG can be improved with orders of magnitude.

Review of triazole scaffolds for treatment and diagnosis of Alzheimer's disease.

Triazole scaffolds, a series of 5-membered heterocycles, are well known for their high efficacy, low toxicity, and superior pharmacokinetics. Alzheimer's disease (AD) is the first neurodegenerative disorder with complex pathological mechanisms. Triazole, as an aromatic group with three nitrogen atoms, forms polar and non-polar interactions with diverse key residues in the receptor-ligand binding procedure, and has been widely used in the molecular design in the development of anti-AD agents.

The effect of transcranial magnetic stimulation on the recovery of attention and memory impairment following stroke: a systematic review and meta-analysis.

Background: Previous studies indicated inconsistent results for the treatment effect of repetitive transcranial magnetic stimulation (rTMS) on attention and memory impairment following stroke.

Methods: Randomized controlled trials (RCTs) on TMS for the treatment of stroke were retrieved from Online databases. Data were analyzed by RevMan 5.

Cooling of mechanical resonator in a hybrid intracavity squeezing optomechanical system.

A hybrid intracavity squeezing optomechanical cooling system, in which an auxiliary cavity couples to an optomechanical cavity with a nonlinear medium inside it, is proposed to realize the ground state cooling of the mechanical resonator in the highly unresolved sideband regime. We demonstrate that the quantum backaction heating can be suppressed perfectly by the intracavity squeezing, and the cooling process can be further promoted by adjusting the tunnel coupling between the coupled cavities. The scheme has good performance in resisting the environmental thermal noise and better tolerance for the auxiliary cavity quality factor and provides the possibility for the quantum manipulation of the mechanical resonator with large mass and low frequency.

Superior treatment efficacy of neuromodulation rehabilitation for upper limb recovery after stroke: a meta-analysis.

Background: This study aims to explore the treatment efficacy of different motor rehabilitation interventions for upper limb impairment recovery.

Research Design & Methods: Publications were searched in PubMed and Embase. 4 grouped motor rehabilitation treatments (training, technological intervention, pharmacological intervention, and neuromodulation) were compared.

Medicinal Prospects of Targeting Tyrosinase: A Feature Review.

Tyrosinase is a bifunctional polyphenol oxidase (PPO), catalyzing two oxidative reactions: monophenols to o-quinones (monophenolase activity) and o-diphenols to oquinones (diphenolase activity). As tyrosinase is the rate-limiting enzyme for the melanogenesis process, it is an attractive target for melanogenesis inhibition. Aiming at skin whitening, anticancer, Parkinson's disease (PD) treatment, antibacterial, fruit and vegetable preservation and other anti-pigmentation effect, medicinal chemists have exploited diverse tyrosinase inhibitors through various approaches.

A highly effective and stable butyrylcholinesterase inhibitor with multi-faceted neuroprotection and cognition improvement.

Butyrylcholinesterase (BChE) has been more and more attractive for treating neurodegenerative diseases, especially Alzheimer's disease (AD). In this study, we conducted activity and druggability optimization based on the structures that were previously reported. Most compounds exhibited pronounced BChE inhibitory capacity with nanomolar IC values.

Discovery of Resorcinol-Based Polycyclic Structures as Tyrosinase Inhibitors for Treatment of Parkinson's Disease.

Tyrosinase is involved in the synthesis of neuromelanin in the substantia nigra, which is closely correlated with the pathogenesis of Parkinson's disease. Herein, we identified (l-Tyr, IC = 6.25 ± 1.

Strategies for Structural Modification of Small Molecules to Improve Blood-Brain Barrier Penetration: A Recent Perspective.

In the development of central nervous system (CNS) drugs, the blood-brain barrier (BBB) restricts many drugs from entering the brain to exert therapeutic effects. Although many novel delivery methods of large molecule drugs have been designed to assist transport, small molecule drugs account for the vast majority of the CNS drugs used clinically. From this perspective, we review studies from the past five years that have sought to modify small molecules to increase brain exposure.

Highly Potent and Selective Butyrylcholinesterase Inhibitors for Cognitive Improvement and Neuroprotection.

Butyrylcholinesterase (BChE) has been considered as a potential therapeutic target for Alzheimer's disease (AD) because of its compensation capacity to hydrolyze acetylcholine (ACh) and its close association with Aβ deposit. Here, we identified (BChE IC = 16 nM) and (BChE IC = 25 nM) as highly effective and selective BChE inhibitors, which were proved to be safe and long-acting. Candidate compounds exhibited neuroprotective effects and the ability to improve cognition in scopolamine- and Aβ peptide-induced cognitive deficit models.

Discovery and Biological Evaluation of a Novel Highly Potent Selective Butyrylcholinsterase Inhibitor.

To discover novel BChE inhibitors, a hierarchical virtual screening protocol followed by biochemical evaluation was applied. The most potent compound (BChE IC = 0.18 ± 0.

Design, synthesis and biological evaluation of novel carboline-cinnamic acid hybrids as multifunctional agents for treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a complex neurodegenerative disease with multiple pathological features. Multifunctional compounds able to simultaneously interact with several pathological components have been considered as a solution to treat the complex pathologies of neurodegenerative diseases. β-carboline and cinnamic acid have been extensively studied for their widespread biological effects in treatment of AD, further application is limited due to its poor solubility and high toxicity.

Transparency and tunable slow-fast light in a hybrid cavity optomechanical system.

We theoretically investigate the optomechanically induced transparency (OMIT) phenomenon in a hybrid optomechanical system composing of an optomechanical cavity and a traditional one. A Kerr medium is inserted in the optomechanical cavity and the other traps the atomic ensemble. We demonstrate the appearance of electromagnetically and optomechanically induced transparency when there is only Kerr medium or atoms in the system.

Reasonably activating Nrf2: A long-term, effective and controllable strategy for neurodegenerative diseases.

Neurodegenerative diseases are a variety of debilitating and fatal disorder in central nervous system (CNS). Besides targeting neuronal activity by influencing neurotransmitters or their corresponding receptors, modulating the underlying processes that lead to cell death, such as oxidative stress and mitochondrial dysfunction, should also be emphasized as an assistant strategy for neurodegeneration therapy. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has been closely verified to be related to anti-inflammation and oxidative stress, rationally regulating its belonging pathway and activating Nrf2 is emphasized to be a potential treatment approach.

Dynamic generation of multi-qubit entanglement in the ultrastrong-coupling regime.

We propose a dynamic evolution protocol for generating multi-qubit GHZ states in the ultrastrong-coupling regime of circuit QED. By varying the time length of sequences, the protocol works for any coupling strength g/ω ≥ 0.25.

Design, synthesis and evaluation of novel bivalent β-carboline derivatives as multifunctional agents for the treatment of Alzheimer's disease.

To develop potent multi-target ligands against Alzheimer's disease (AD), a series of novel bivalent β-carboline derivatives were designed, synthesized, and evaluated. In vitro studies revealed these compounds exhibited good multifunctional activities. In particular, compounds 8f and 8g showed the good selectivity potency on BuChE inhibition (IC = 1.

High-speed quantum-random number generation by continuous measurement of arrival time of photons.

We demonstrate a novel high speed and multi-bit optical quantum random number generator by continuously measuring arrival time of photons with a common starting point. To obtain the unbiased and post-processing free random bits, the measured photon arrival time is converted into the sum of integral multiple of a fixed period and a phase time. Theoretical and experimental results show that the phase time is an independent and uniform random variable.

Four-level refrigerator driven by photons.

We propose a quantum absorption refrigerator driven by photons. The model uses a four-level system as its working substance and couples simultaneously to hot, cold, and solar heat reservoirs. Explicit expressions for the cooling power Q̇(c) and coefficient of performance (COP) η(COP) are derived, with the purpose of revealing and optimizing the performance of the device.

Multi-bit quantum random number generation by measuring positions of arrival photons.

We report upon the realization of a novel multi-bit optical quantum random number generator by continuously measuring the arrival positions of photon emitted from a LED using MCP-based WSA photon counting imaging detector. A spatial encoding method is proposed to extract multi-bits random number from the position coordinates of each detected photon. The randomness of bits sequence relies on the intrinsic randomness of the quantum physical processes of photonic emission and subsequent photoelectric conversion.

Thermal Brownian motor coupled by Casimir interaction.

We study a Feynman-like thermal Brownian motor, in which the asymmetric corrugated cylinder as the ratchet is coupled with a corrugated plate by the noncontact Casimir interaction between them. The source of driving of the system is the thermal fluctuations and its dynamic evolution is described by a set of Langevin equations. Further, the mean velocity and thermal efficiency of the motor in the overdamped limit are studied in detail as a function of the temperature of the baths, external load applied, magnitude of the Casimir interaction, and other relevant parameters by the numerical stimulation.

Outcomes of a randomized trial of continuum of care services for children in a child welfare system.

The Connecticut Department of Children and Families Title IV-E waiver demonstration evaluated whether the well-being of children approved for residential mental health services could be improved, and lengths of stay in restrictive placements reduced, by providing case rate payments to community agencies to provide continuum of care services. Children between ages 7 and 15 were randomly assigned to either the demonstration group (n = 78) or to usual state-supported services (n = 79). One-year outcome results indicated that in a situation that is less costly, improvement in outcomes occurred in less restrictive settings.