Rational Design and Multibiological Profiling of Novel Donepezil-Trolox Hybrids against Alzheimer's Disease, with Cholinergic, Antioxidant, Neuroprotective, and Cognition Enhancing Properties.

A novel series of donepezil-trolox hybrids were designed, synthesized, and evaluated as multifunctional ligands against Alzheimer's disease (AD). Biological assays showed that these derivatives possessed moderate to good inhibitory activities against acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B) as well as remarkable antioxidant effects. The optimal compound 6d exhibited balanced functions with good inhibition against hAChE (IC = 0.

Novel cinnamamide-dibenzylamine hybrids: Potent neurogenic agents with antioxidant, cholinergic, and neuroprotective properties as innovative drugs for Alzheimer's disease.

By using fragments endowed with interesting and complementary properties for the treatment of Alzheimer's disease (AD), a novel series of cinnamamide-dibenzylamine hybrids have been designed, synthesized, and evaluated biologically. In vitro assay indicated that most of the target compounds exhibited a significant ability to inhibit ChEs, strong potency inhibitory of self-induced β-amyloid (Aβ) aggregation and to act as potential antioxidants and biometal chelators. A Lineweaver-Burk plot and molecular modeling study showed that compound 7f targeted both the CAS and PAS of AChE.

Design, synthesis and evaluation of coumarin-pargyline hybrids as novel dual inhibitors of monoamine oxidases and amyloid-β aggregation for the treatment of Alzheimer's disease.

A series of coumarin-pargyline hybrids (4a-x) have been designed, synthesized and evaluated as novel dual inhibitors of Alzheimer's disease (AD). Most of the compounds exhibited a potent ability to inhibit amyloid-β (Aβ) aggregation and monoamine oxidases. In particular, compound 4x exhibited remarkable inhibitory activities against monoamine oxidases (IC, 0.

Smartphone-based cyclic voltammetry system with graphene modified screen printed electrodes for glucose detection.

Smartphone-based electrochemical devices have such advantages as the low price, miniaturization, and obtaining the real-time data. As a popular electrochemical method, cyclic voltammetry (CV) has shown its great practicability for quantitative detection and electrodes modification. In this study, a smartphone-based CV system with a simple method of electrode modification was constructed to perform electrochemical detections.

Pressure induced polymerization of acetylide anions in CaC and 10 fold enhancement of electrical conductivity.

Transformation between different types of carbon-carbon bonding in carbides often results in a dramatic change of physical and chemical properties. Under external pressure, unsaturated carbon atoms form new covalent bonds regardless of the electrostatic repulsion. It was predicted that calcium acetylide (also known as calcium carbide, CaC) polymerizes to form calcium polyacetylide, calcium polyacenide and calcium graphenide under high pressure.

Synthesis and pharmacological evaluation of novel chromone derivatives as balanced multifunctional agents against Alzheimer's disease.

In a continuing effort to develop multitargeted compounds as potential treatment agents against Alzheimer's disease (AD), a series of chromone derivatives were designed, synthesized and evaluated. In vitro assay indicated that most of the target compounds have both MAOs inhibition activities, antioxidant activity and biometal chelating ability. Especially, compound s19 exhibits good inhibitory potency for inhibition of MAOs (IC value of 5.

Synthesis and pharmacological evaluation of multi-functional homoisoflavonoid derivatives as potent inhibitors of monoamine oxidase B and cholinesterase for the treatment of Alzheimer's disease.

A series of homoisoflavonoid derivatives was designed, synthesized and evaluated as potential multi-functional anti-Alzheimer's agents for their inhibitory activity on cholinesterase and monoamine oxidase. Among them, compound showed moderate acetylcholinesterase (AChE) inhibitory activity (eeAChE IC = 0.89 ± 0.

Cannabidiol administration reduces sublesional cancellous bone loss in rats with severe spinal cord injury.

Patients with spinal cord injury (SCI) undergo severe loss of bone mineral below the level of lesion, and data on available treatment options after SCI is scarce. The aim of this work was to investigate the therapeutic effect of cannabidiol (CBD), a non-psychoactive cannabis, on sublesional bone loss in a rat model of SCI. The adult male rats were exposed to surgical transection of the cord and treated with CBD for consecutive 14 days.

g-CN/AgBr nanocomposite decorated with carbon dots as a highly efficient visible-light-driven photocatalyst.

Visible-light-driven photocatalysis as a green technology has attracted intense interest due to its potential applications in environmental remediation. However, the poor visible light utilization and low electron-hole separation efficiency of photocatalysts largely limited their practical application. In this work, a new ternary visible-light driven photocatalyst of g-CN/CDs/AgBr has been prepared by the introduction of carbon dots (CDs) onto the surface of g-CN, followed by in-situ growth of AgBr nanoparticles on CDs-modified g-CN nanosheets.

Cortical regulation of striatal projection neurons and interneurons in a Parkinson's disease rat model.

Striatal neurons can be either projection neurons or interneurons, with each type exhibiting distinct susceptibility to various types of brain damage. In this study, 6-hydroxydopamine was injected into the right medial forebrain bundle to induce dopamine depletion, and/or ibotenic acid was injected into the M1 cortex to induce motor cortex lesions. Immunohistochemistry and western blot assay showed that dopaminergic depletion results in significant loss of striatal projection neurons marked by dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein, molecular weight 32 kDa, calbindin, and μ-opioid receptor, while cortical lesions reversed these pathological changes.

Development, comparison and application of sorbent-assisted accelerated solvent extraction, microwave-assisted extraction and ultrasonic-assisted extraction for the determination of polybrominated diphenyl ethers in sediments.

Fast and selective analytical methods were developed based on sorbent-assisted mechanism and microwave-assisted extraction (SA-MAE), accelerate solvent extraction (SA-ASE) and ultrasonic-assisted extraction (SA-UAE) for the determination of polybrominated diphenyl ethers (PBDEs) in sediments. The experimental parameters, such as extraction conditions and sorbent amounts, were optimized according to Taguchi Orthogonal Arrays. The accuracy of developed SA-methods was a satisfactory ranging from 71% to 118%.

Molecular Role of EGFR-MAPK Pathway in Patchouli Alcohol-Induced Apoptosis and Cell Cycle Arrest on A549 Cells and .

Nowadays, chemotherapy is still the main effective treatment for cancer. Herb prescriptions containing (also known as "Guang-Huo-Xiang") have been widely used in Chinese medicine today. In our research, we found that patchouli alcohol, a compound isolated from the oil of , exerted antitumor ability against human lung cancer A549 cells ability both and .

Tetramethylpyrazine Promotes Migration of Neural Precursor Cells via Activating the Phosphatidylinositol 3-Kinase Pathway.

Stem cell therapy may provide a novel therapeutic method for the replacement and regeneration of damaged neural cells in the central nervous system. However, insufficient stem cell migrating into the injured regions limits its applications. Although tetramethylpyrazine (TMP) originally isolated from Ligusticum walliichi (Chuanxiong) has been widely used to treat ischemic stroke in the clinic for many years because of its role in neuroprotection, how TMP impacts the migration of neural progenitor/precursor cells (NPCs) and what is the underlying cellular and molecular mechanism remain largely unknown.

Neuroprotective effects of benzyloxy substituted small molecule monoamine oxidase B inhibitors in Parkinson's disease.

The benzyloxy substituted small molecules are well-known highly potent monoamine oxidase B inhibitors, but their therapeutic potential against Parkinson's disease have not been investigated in detail. In this paper, a series of representative benzyloxy substituted derivatives were synthesized and evaluated for MAO-A/B inhibition. In addition, their neuroprotective effects were investigated in 6-OHDA- and rotenone-treated PC12 cells.

D-Phenylalanine inhibits biofilm development of a marine microbe, Pseudoalteromonas sp. SC2014.

D-Amino acids have been reported to be able to inhibit biofilm formation or disperse existing biofilms of many microbes; in some cases this is due to growth inhibition as an unspecific effect. In this work, six different D-amino acids were tested for their inhibitory effects on biofilm development and bacterial growth of Pseudoalteromonas sp. SC2014, a marine microbe involved in microbiologically influenced corrosion (MIC).

A Comparative Study of Three Interneuron Types in the Rat Spinal Cord.

Interneurons are involved in the physiological function and the pathomechanism of the spinal cord. Present study aimed to examine and compare the characteristics of Cr+, Calb+ and Parv+ interneurons in morphology and distribution by using immunhistochemical and Western blot techniques. Results showed that 1) Cr-Calb presented a higher co-existence rate than that of Cr-Parv, and both of them were higher in the ventral horn than in the dosal horn; 2) Cr+, Calb+ and Parv+ neurons distributing zonally in the superficial dosal horn were small-sized.

Not leaving home: grandmothers and male dispersal in a duolocal human society.

Models suggest that dispersal patterns will influence age- and sex-dependent helping behavior in social species. Duolocal social systems (where neither sex disperses and mating is outside the group) are predicted to be associated with mothers favoring sons over daughters (because the latter are in reproductive competition with each other). Other models predict daughter-biased investment when benefits of wealth to sons are less than daughters.

Efficient streptavidin-functionalized nitrogen-doped graphene for the development of highly sensitive electrochemical immunosensor.

In this work, an efficient and universal streptavidin-functionalized nitrogen-doped graphene (NG) was for the first time proposed and used to develop a highly sensitive electrochemical immunosensor for the detection of tumor markers. Transmission electron microscopy, electrochemical impedance spectrum, static water contact measurement, and cyclic voltammetry were used to characterize the streptavidin-functionalized NG platform and immunosensor. The biofunctionalized NG showed excellent hydrophilicity, larger specific surface area, and high electrochemical activity.

Monitoring the electrochemical responses of neurotransmitters through localized surface plasmon resonance using nanohole array.

In this study, a novel spectroelectrochemical method was proposed for neurotransmitters detection. The central sensing device was a hybrid structure of nanohole array and gold nanoparticles, which demonstrated good conductivity and high localized surface plasmon resonance (LSPR) sensitivity. By utilizing such specially-designed nanoplasmonic sensor as working electrode, both electrical and spectral responses on the surface of the sensor could be simultaneously detected during the electrochemical process.

Dihydromyricetin Ameliorates 3NP-induced Behavioral Deficits and Striatal Injury in Rats.

Oxidative stress is closely involved in neurodegenerative diseases. The present study aimed to examine the effect of anti-oxidant DHM (dihydromyricetin) on 3NP (3-nitropropionic acid) -induced behavioral deficits of experimental rats and striatal histopathological injury by using behavioral, imaging, biochemistry, histochemistry and molecular biology technologies. The experimental results showed that both motor dysfunctions and learning and memory impairments induced by 3NP were significantly reduced after DHM treatment.

Rational modification of donepezil as multifunctional acetylcholinesterase inhibitors for the treatment of Alzheimer's disease.

A series of novel donepezil derivatives was designed, synthesized and evaluated as multifunctional acetylcholinesterase (AChE) inhibitors for the treatment of Alzheimer's disease (AD). The screening results indicated that most of the compounds exhibited potent inhibition of AChE with IC50 values in the nanomolar range. Moreover, these derivatives displayed good antioxidant, Aβ interaction, blood-brain barrier penetration (PAMPA-BBB+) and ADMET properties (in silico).

Synthesis and evaluation of multi-target-directed ligands for the treatment of Alzheimer's disease based on the fusion of donepezil and melatonin.

A novel series of compounds obtained by fusing the acetylcholinesterase (AChE) inhibitor donepezil and the antioxidant melatonin were designed as multi-target-directed ligands for the treatment of Alzheimer's disease (AD). In vitro assay indicated that most of the target compounds exhibited a significant ability to inhibit acetylcholinesterase (eeAChE and hAChE), butyrylcholinesterase (eqBuChE and hBuChE), and β-amyloid (Aβ) aggregation, and to act as potential antioxidants and biometal chelators. Especially, 4u displayed a good inhibition of AChE (IC50 value of 193nM for eeAChE and 273nM for hAChE), strong inhibition of BuChE (IC50 value of 73nM for eqBuChE and 56nM for hBuChE), moderate inhibition of Aβ aggregation (56.

Synthesis and pharmacological evaluation of donepezil-based agents as new cholinesterase/monoamine oxidase inhibitors for the potential application against Alzheimer's disease.

In a continuing effort to develop multitargeted compounds as potential treatment agents against Alzheimer's disease (AD), a series of donepezil-like compounds were designed, synthesized and evaluated. In vitro studies showed that most of the designed compounds displayed potent inhibitory activities toward AChE, BuChE, MAO-B and MAO-A. Among them, w18 was a promising agent with balanced activities, which exhibited a moderate cholinesterase inhibition (IC, 0.

Single-point mutation-mediated local amphipathic adjustment dramatically enhances antibacterial activity of a fungal defensin.

The emergence and rapid spread of multiresistant bacteria has lead to an urgent need for novel antimicrobials. Based on single-point substitutions, we generated a series of mutants of micasin, a dermatophytic defensin, with enhanced activities against multiple clinical isolates of Staphylococcus species, including 4 antibiotic-resistant strains. We first mapped the functional surface of micasin by alanine-scanning mutational analysis of its highly exposed residues, through which we found that substitution of site 8 (acidic Glu) dramatically enhanced bacterial killing of this peptide.

Kinship as a frequency dependent strategy.

Humans divide themselves up into separate cultures, which is a unique and ubiquitous characteristic of our species. Kinship norms are one of the defining features of such societies. Here we show how norms of marital residence can evolve as a frequency-dependent strategy, using real-world cases from southwestern China and an evolutionary game model.