Genetic Variants of the MTMR9 Gene Are Associated with Nonspecific Intellectual Disability: A Family-Based Association Study.

Background: Mutations within the myotubularin-related protein 9 gene (MTMR9) have been identified in several families with nonsyndromic intellectual disability (NSID), a generalized neurodevelopmental disorder; however, the relationship between MTMR9 and NSID needs to be verified using a larger sample size. Aim: To explore whether genetic variants in the MTMR9 gene are linked to susceptibility of NSID among the Chinese population. Materials and Methods: Seven single nucleotide polymorphisms (SNPs) of the MTMR9 gene (rs4559208, rs3824211, rs2164272, rs2164273, rs1897951, rs6991606, and rs7815802) were analyzed using family-based association testing among 258 Han Chinese NSID families. Results: Three SNPs of MTMR9 were significantly associated with NSID (z = 2.152, p = 0.031 for rs4559208; z = 2.403, p = 0.016 for rs2164273; and z = 2.758, p = 0.006 for rs7815802). Three alleles of these SNPs were more likely to be transferred from the carrier parents to the affected offspring. Haplotypes constructed using these SNPs also showed a similar transmitting trend (z = 2.505, p = 0.012, χ2(3) = 8.835, and global p = 0.032). Carriers with the G-G-C haplotype showed a higher risk of NSID (odds ratio = 1.46, 95% confidence interval [1.01-2.09], p = 0.04) than others. In silico functional predictions supported an etiological role for these three SNPs in NSID biology. Conclusions: This study provides additional insights into the association of NSID with specific alleles, and haplotypes within the MTMR9 gene. Genotypic analyses of the MTMR9 gene should be considered for patients presenting with NSID of unknown etiology.

Prediction of Alzheimer's disease with serum lipid levels in Asian individuals: a meta-analysis.

Background: The serum lipid profile has become a routine clinical test and used as an important predictor for Alzheimer's disease (AD), although its predictive value remains undetermined. Objective: To evaluate the role of serum lipid levels in predicting the risk of AD. Methods: Meta-analyses were conducted using Comprehensive Meta-analyses (CMA) software to investigate the association between four conventional serum lipid profile parameters and the risk of AD, focused on samples from Asian. Results: In total, 3423 AD patients and 6127 healthy participants were involved. The results demonstrated that AD patients showed higher LDL-C and TC levels (SMD = 0.27, 95% CI: 0.04-0.51, p = 0.02 for LDL-C; SMD = 0.25, 95% CI: 0.05-0.46, p = 0.02 for TC) compared with those of healthy controls. People with higher LDL-C and/or TC levels had an increased risk of AD (OR = 1.64, 95% CI: 1.07-2.51 for LDL-C and OR = 1.58, 95% CI: 1.10-2.92 for TC). Conclusions: This study provided evidence that serum LDL-C and TC levels were associated with the risk of AD in Asian individuals. The routine lipid profile may be useful for AD diagnosis, monitoring and treatment.

Silsesquioxane stabilized platinum-palladium alloy nanoparticles with morphology evolution and enhanced electrocatalytic oxidation of formic acid.

Bimetallic catalysts have attracted enormous attention with their enhanced electrocatalytic properties in fuel cells. Herein a series of silsesquioxane (POSS) stabilized platinum-palladium (PtPd) alloy nanoparticles (NPs) with morphology evolution were facilely synthesized with the co-chemical reduction using formaldehyde as the reductant. By varying the ratio of Pt to Pd, the PtPd alloy NPs evolved from truncated octahedrons to octahedrons, and triangular nanoplates. The mechanism of morphology evolution is that Pt and Pd could self-assemble on POSS to form PtxPd1-x intermediates with different Pt/Pd ratios. In addition, formaldehyde could selectively bind to the {1 1 1} facets of Pd to control the growth rates of different facets and help PtxPd1-x intermediates with different Pt/Pd ratio grow into different morphology of PtxPd1-x alloys. The morphology tuning endowed the PtPd alloy NPs superior performance for formic acid electrooxidation. Compared with Pt, Pd NPs, and commercial Pt/C catalyst, the PtPd alloy NPs displayed larger electrochemically active surface area, enhanced electrocatalytic activity and durability toward oxidation of formic acid, and increased CO tolerance. This work suggested that modification of catalytic activity through morphology tuning with composition adjustment might provide some new pathways for the design of promising catalysts with advanced performance.

Non-covalent interaction between dietary stilbenoids and human serum albumin: Structure-affinity relationship, and its influence on the stability, free radical scavenging activity and cell uptake of stilbenoids.

Dietary stilbenoids are associated with many benefits for human health, which depend on their bioavailability and bioaccessibility. The stilbenoid-human serum albumin (HSA) interactions are investigated to explore the structure-affinity relationship and influence on the stability, free radical scavenging activity and cell uptake of stilbenoids. The structure-affinity relationship of the stilbenoids-HSA interaction was found as: (1) the methoxylation enhanced the affinity, (2) an additional hydroxyl group increases the affinity and (3) the glycosylation significantly weakened the affinity. HSA obviously masked the free radical scavenging potential of stilbenoids. The stabilities of stilbenoids in different medium were determined as: HSA solution>human plasma>Dulbecco's modified Eagle's medium. It appears that the milk enhanced the cell uptake of stilbenoids with multi-hydroxyl groups and weakened the cell uptake of stilbenoids with methoxyl group on EA.hy 926 endothelial cells. The stilbenoids are hardly absorbed by human umbilical vein endothelial cells in the presence of milk.

Interaction between Z-ligustilide from Radix Angelica sinensis and human serum albumin.

Z-ligustilide (LIG), an essential oil extract from Radix Angelica sinensis, has broad pharmaceutical applications in treating cardiovascular and cerebrovascular diseases. Interaction of LIG with the major transport protein of human blood circulation, human serum albumin (HSA) has been investigated by steady-state, UV-vis and circular dichroism (CD) spectroscopic methods, as well as the effect of metal ions (e.g. Zn(2+), Cu(2+), Fe(3+), Co(2+), Ni(2+)) on the LIG-HSA system. Fluorescence results revealed that a moderate binding affinity (1.59 × 10(4) M(-1) at 298 K) between LIG and HSA with a 1:1 stoichiometry. Thermodynamic analysis of the binding data (ΔS = +12.96 J mol(-1) K(-1) and ΔH =- 20.11 kJ mol(-1)) suggested the involvement of hydrophobic and van der Waals forces, as well as hydrogen bonding in the complex formation. The specific binding distance r (3.75 nm) between donor (Trp-214) and acceptor (LIG) was obtained according to fluorescence resonance energy transfer. CD results showed that slight conformational changes occurred in the protein upon complexation with LIG.

Two macrocyclic polyamines as modulators of metal-mediated Aß40 aggregation.

Dysfunctional interactions of amyloid-ß (Aß) with Zn and Cu ions are proved to be related to the etiology of Alzheimer's disease (AD). Disruption of these metal-Aß interactions using metal chelators holds considerable promise as a therapeutic strategy to combat this incurable disease. Herein, we report that two cyclam derivatives (L1 and L2) are capable of modulating Zn(2+)/Cu(2+)-mediated Aß40 aggregation, reactive oxygen species (ROS) production, and neurotoxicity. These chelators were found to inhibit the metal-induced Aß40 aggregation, dissociate metal-Aß40 aggregates and restore the metal-induced ß-sheet structure of Aß40 to its random coil conformation, as observed by BCA protein assay, thioflavin T fluorescence and circular dichroism spectroscopy. Moreover, preliminary investigation of SH-SY5Y cells indicates that L1 and L2 can diminish the neurotoxicity of metal-Aß40 species, control metal-Aß40-triggered ROS production and protect cells against apoptosis. These observations warrant the further investigations of L1 and L2 as potential anti-AD agents.

DNA cycle amplification device on magnetic microbeads for determination of thrombin based on graphene oxide enhancing signal-on electrochemiluminescence.

A novel and sensitive strategy which integrated a DNA cycle device onto magnetic microbeads (MB), amplifying the signal with graphene oxide (GO) and enhancing electrochemiluminescence (ECL) intensity, was developed and was further successfully applied to thrombin detection.

Fabrication and characterization of poly(N-isopropyl acrylamide)-gold nanoshell structures.

Novel core-shell structures were presented here which consist of Poly(N-isopropyl acrylamide) (PNIPAM) microspheres as cores and gold as shells. The fabrication of these structures was convenient because the modifications to PNIPAM or gold nanoparticles (GNPs) were omitted. GNPs were attached to the surface of PNIPAM microspheres by means of electrostatic adsorption, and then acted as seeds to grow quickly into complete shells by optimizing the pH of the HAuCl4 solution to control the growth rate of gold nanoshells (GNSs). These structures combine the thermo-responsive behavior of PNIPAM microspheres with optical property of GNSs, and the localized surface plasmon resonance (LSPR) of the GNSs can be changed by adjusting the temperature of the PNIPAM microspheres which make them have great prospects for drug release. Their good biological stability in bovine serum albumin (BSA) and the LSPR located near 700 nm are expected for optical biosensors and optical analysis of whole-blood.

Chitosan as an active support for assembly of metal nanoparticles and application of the resultant bioconjugates in catalysis.

Metal nanoparticle-chitosan (NPs-chitosan) bioconjugates were formed by exposure of chitosan to an aqueous solution of metal salts under thermal treatment. The metal nanoparticles that are formed strongly bound to chitosan, which encouraged us to investigate their catalytic performance. It was demonstrated that the metal NPs-chitosan bioconjugates functioned as effective catalysts for the reduction of 4-nitrophenol in the presence of NaBH(4), which was monitored by means of spectrophotometry as a function of reaction time. The silver NPs-chitosan bioconjugates exhibited excellent catalytic activity and were reusable for up to seven cycles. In contrast, the gold NPs-chitosan catalyst displayed poor catalytic activity, even in the second cycle. A highlight of our approach is that chitosan simultaneously acts as an active support for the synthesis and assembly of nanoparticles, and the resultant bioconjugates bear the advantage of easy separation from the reaction medium.

A cuttlebone-derived matrix substrate for hydrogen peroxide/glucose detection.

A simple biosensor for hydrogen peroxide (H(2)O(2)) and glucose was fabricated by incorporating gold nanoparticles (GNPs) onto a cuttlebone-derived matrix substrate (CDMS). Such a three-dimensional chamber-like structure naturally bears abundant amino groups for the direct immobilization of GNPs without a series of modifications. And preferably, the framework endows CDMS with a very high surface area for the attachment of GNPs, resulting in effective optical signal transduction and improved sensitivity of the detection system. The principle behind this biosensor is that the localized surface plasmon resonance (LSPR) of the immobilized GNPs changes with the enlargement of GNPs by H(2)O(2)-mediated chemical reduction of chloroauric acid. Using this approach, we demonstrate the proof of an optical biosensor to quantify the concentration of H(2)O(2) as well as glucose. UV-vis absorption spectra were recorded to obtain quantitative information about the H(2)O(2) or glucose concentration. The detection range of our biosensor to H(2)O(2) concentration was from 2 x 10(-6) to 1.5 x 10(-4)M, while the linear response range of glucose concentration was from 5 x 10(-6) to 5 x 10(-5)M. Inspiringly and interestingly, the growth of GNPs on CDMS gives rise to color changes, this phenomenon shows that the rapid detection by our sensor has the superiority in visual detection to a certian extent, which has been a potential application in qualitative or semiquantitative analysis for medicine and biotechnology.

[Chitosan and its applications in synthesis of metal nanomaterials].

Chitosan has natural abundance, unique bioactivity and attractive physicochemical properties. Recent years, the synthesis of chitosan-based metal nanomaterials has attracted increasing attention. The synthesis of metal nanoparticles utilizing biomolecular or organism offers a mild medium, and thus a greater degree of control over the nanoparticles produced, along with higher reproducibility. In particular, preparation of metal nanoparticles based on biomolecular or organism has its unique facility in integrating "minimum feature sizes" into labile biological components to an excellent synergy and bifunctional effect and consequently a more broad application. Herein, we review the new development of chitosan, chitosan-based synthesis of metal nanomaterials, and their application.

Cuttlebone-derived organic matrix as a scaffold for assembly of silver nanoparticles and application of the composite films in surface-enhanced Raman scattering.

Biologically derived materials provide a rich variety of approaches toward new functional materials because of their fascinating structures and environment-friendly features, which is currently a topic of research interest. In this paper, we show that the cuttlebone-derived organic matrix (CDOM) is an excellent scaffold for the one-step synthesis and assembly of silver nanoparticles (AgNPs), which can be further used as substrate for surface-enhanced Raman scattering (SERS). Formation of AgNPs-CDOM composite was accomplished by the reaction of CDOM with AgNO(3) and NH(3).H(2)O solution at 80 degrees C without using any other stabilizer and reducing agents. UV-vis spectra and TEM were utilized to characterize the AgNPs and investigate their formation process. Results demonstrate that the size and distribution of AgNPs can be partly regulated by changing incubation time; the concentration of NH(3).H(2)O is critical to the formation rate of AgNPs. As a proof of principle, we show that the AgNPs-CDOM composite can be employed in trace analysis using SERS.

Simultaneous synthesis and assembly of gold nanoparticles in cuttlebone-derived organic matrix: a "green" pathway for gold nanocomposite.

We demonstrate herein a "green" pathway for the formation of a gold nanocomposite using the cuttlebone-derived organic matrix. The gold nanocomposite is achieved through the first exposure of the organic matrix to HAuCl4 solution at room temperature and its subsequent heating at 80 degrees C. The process results in the formation of a macro porous gold nanocomposite consisting of gold nanoparticles embedded in the cuttlebone-derived organic matrix background, which shows the characteristic plasma absorption of gold nanostructures. UV-vis-IR spectrophotometer and transmission electron microscope (TEM) were used to characterize the gold nanocomposite and trace the formation process. A highlight of the research is that we adopted a nontoxic and renewable reagent of cuttlebone-derived organic matrix, which functioned as the reducing reagent, stabilizer and scaffold for the synthesis of gold nanoparticles.