Prion neurotoxicity

Although the mechanisms underlying prion propagation and infectivity are now well established, the processes accounting for prion toxicity and pathogenesis have remained mysterious. These processes are of enormous clinical relevance as they hold the key to identification of new molecular targets for therapeutic intervention. In this review, we will discuss two broad areas of investigation relevant to understanding prion neurotoxicity. The first is the use of in vitro experimental systems that model key events in prion pathogenesis. In this context, we will describe a hippocampal neuronal culture system we developed that reproduces the earliest pathological alterations in synaptic morphology and function in response to PrP^Sc. This system has allowed us to define a core synaptotoxic signaling pathway involving the activation of NMDA and AMPA receptors, stimulation of p38 MAPK phosphorylation and collapse of the actin cytoskeleton in dendritic spines. The second area concerns a striking and unexpected phenomenon in which certain structural manipulations of the PrP^C molecule itself, including introduction of N‐terminal deletion mutations or binding of antibodies to C‐terminal epitopes, unleash powerful toxic effects in cultured cells and transgenic mice. We will describe our studies of this phenomenon, which led to the recognition that it is related to the induction of large, abnormal ionic currents by the structurally altered PrP molecules. Our results suggest a model in which the flexible N‐terminal domain of PrP^C serves as a toxic effector which is regulated by intramolecular interactions with the globular C‐terminal domain. Taken together, these two areas of study have provided important clues to underlying cellular and molecular mechanisms of prion neurotoxicity. Nevertheless, much remains to be done on this next frontier of prion science.     

Effect of Aryl Substituents and Fluorine Addition on the Optoelectronic Properties and Organic Solar Cell Performance of a High Efficiency Indacenodithienothiophene‐alt‐Quinoxaline π‐Conjugated Polymer

A series of donor‐acceptor (D‐A) π‐conjugated polymers, based on indacenodithienothiophene (IDTT) as an electron‐donating unit and quinoxaline as an electron‐deficient moiety, are synthesized via a Pd‐catalyzed Stille cross‐coupling polymerization. Molecular characteristics, photovoltaic parameters, and optoelectronic properties are examined through structural differences corresponding to thienyl versus phenyl side group substitutions on the IDTT and the non‐fluorinated versus the monofluoro quinoxaline derivatives. One of the most important outcome is that the power conversion efficiency (PCE) in the studied polymers is more device architecture dependent (conventional vs inverted) rather than chemical structure dependent. From single junction solar cells based on bulk heterojunction polymer:[6,6]‐phenyl‐C₇₁‐butyric acid methyl ester (PC₇₁BM) systems as the active layer, a maximum PCE of 5.33% has been achieved from the polymer containing the thienyl substituent on the IDTT and one fluorine atom on the quinoxaline. This demonstrates that finding the optimum molecular weight of ThIDTT‐QF or introducing the monofluoro‐quinoxaline in a regioregular motif in the polymer backbone significantly higher PCE can be expected versus the fully optimized high performance PhIDTT‐Q conjugated polymer.     

Gallol‐Tethered Injectable AuNP Hydrogel with Desirable Self‐Healing and Catalytic Properties

Injectable self‐healing hydrogels have drawn growing attention for their extensive applications in biomedical fields. Hydrogels containing nanoparticles also exhibit promising potentials in catalysis, wastewater treatment, and organic synthesis. Inspired by the multifunction of gallol presented herein, a simple one‐pot method to produce a gallol‐tethered gelatin hydrogel via Schiff base under oxidizing conditions using various oxidants is presented. The hydrogels prepared by NaIO₄‐induced cross‐linking present a high self‐healing rate (up to 84.5%), injectable ability, tunable mechanical property, flexible viscoelasticity, and macroporous structure owing to the combination of covalent cross‐linking and supramolecular interactions. HAuCl₄ contributes to the 3D structure formation of the gelatin hydrogel via oxidation cross‐linking. It is reduced by the gallol groups to produce nanogold (AuNP)‐decorated hydrogel (Au‐gel). This Au‐gel is fully characterized by UV–vis, XRD, TEM, SEM, EDX, and ICP‐MS and exhibits a high‐catalytic activity for the reduction of 4‐nitrophenol. The solid Au‐gel catalyst is robust, easily recyclable, and reused at least eight times.     

Visible Light Controlled Polymerization of Azide‐Derived Monomers: A Facile,Metal‐Free PET‐ATRP Route to Construct Azide Polymers

Well‐defined azide polymers are successfully synthesized by visible‐light‐induced metal‐free electron transfer–atom transfer radical polymerization (PET‐ATRP) at room temperature. This technique uses Eosin Y/Et₃N as the reductive quenching photocatalyst system, which can effectively prevent the destruction of the azide group in polymerization. Four kinds of azide‐derived monomers participate well in this reaction and obtain satisfactory results. The kinetic behavior, “ON/OFF” experiment, and chain‐extension experiment confirm the living feature of this visible light controlled polymerization. Moreover, random copolymers obtained by this protocol can be used as surface modifier which further demonstrates the utility and reliability of this method.     

Preparation of Light‐Responsive Aliphatic Polycarbonate via Versatile Polycondensation for Controlled Degradation

Starting from (2,2,5‐trimethyl‐1,3‐dioxan‐5‐yl)methanamine with light‐responsive 4,5‐dimethoxy‐2‐nitrobenzyl protecting groups, a variety of light‐responsive copolycarbonates (LrPCs) are synthesized by a general two‐step polycondensation using lithium acetylacetonate (LiAcac) as catalyst. UV/Vis, ¹H nuclear magnetic resonance (NMR), and size exclusion chromatography (SEC) confirm the rapid decomposition of these polymers in response to irradiation with UV light. Stable and monodisperse nanoparticles with hydrodynamic diameters of 100 nm, formulated from 25% LrPC and 75% poly(lactic‐co‐glycolic acid) (PLGA), undergo rapid disruption upon triggering with UV light, while standard PLGA nanoparticles remain stable. Moreover, differing from the ring‐opening polymerization (ROP) of trimethylene carbonate‐based monomers, direct polycondensation of 1,3‐propanediol‐based monomers with pendent functional groups and other diols will enable the introduction of various properties into the polycarbonate backbone, and expand the family of biodegradable synthetic polymers for potential biomedical applications.     

Efficient Production of High‐Quality Polystyrene‐Functionalized Graphene via Graphite Exfoliation in Chloroform with a Heterobifunctional Hyperbranched Polyethylene as Stabilizer

Efficient production of high‐quality, functionalized graphene is highly desirable for large‐scale applications of graphene. Herein, a route for producing high‐quality, polystyrene (PS)‐functionalized graphene is demonstrated via graphite exfoliation in chloroform with a heterobifunctional hyperbranched polyethylene, HBPE@Py@PS, as stabilizer. The HBPE@Py@PS, possessing a pyrene‐functionalized hyperbranched polyethylene backbone and multiple PS side chains, is synthesized by combining chain walking polymerization and atom transfer radical polymerization techniques. It is confirmed that the HBPE@Py@PS can effectively promote graphite exfoliation in chloroform under sonication to render stable dispersions of high‐quality graphene, with an exfoliation efficiency high as 15% and a monolayer proportion, 61%. Meanwhile, it can irreversibly adsorb on the exfoliated graphene surface based on the π–π stacking interactions, concurrently rendering PS‐functionalized graphene that is fluorescent and highly dispersible in chloroform, with a film conductivity reaching 1100 S m^?1. The as‐produced graphene may find its applications as nanofiller for various PS‐based graphene nanocomposites.     

One‐Step Route to Ladder‐Type C–N Linked Conjugated Polymers

A one‐step synthetic method is demonstrated to construct ladder‐type conjugated polymers without the resource to post‐cyclization procedures. The ladder‐type C–N linked conjugated polymers ( P1 and P2 ) and model compounds ( 1 and 2 ) are achieved in high yields. The obtained model compounds and polymers display desirable solubility in commonly used solvents and high thermal stability, which show a promising application in photoelectric material field.     

A Triple‐Shape Memory Material via Thermal Responsive Behavior of Liquid Crystalline Network Incorporating Main‐Chain/Side‐Chain LC Units

In the last several years, multiple‐shape memory liquid crystalline networks (LCNs) have received more and more attention due to the basic theoretical research on them and their wide potential applications. In this article, a novel main‐chain/side‐chain liquid crystalline monomer and its corresponding polymer networks based on the thiol‐ene click reaction are reported. Properties of the synthesized liquid crystalline monomer are well studied with nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) spectra, differential scanning calorimetry (DSC), and polarized optical microscopy (POM). The as‐prepared free‐standing LCN films are investigated well by FTIR, DSC, POM, and X‐ray diffraction (XRD), which show them having good liquid crystalline properties. Tensile test and dynamical mechanical analysis (DMA) results indicate the LCN films have excellent thermal mechanical properties. By adjusting the crosslinking densities, LCN films exhibit two thermal transition temperatures (T_g and T_NI) that can be utilized to trigger the triple‐shape memory behaviors. The cyclic thermal mechanical analysis conducted by DMA reveals that LCN films exhibit good triple‐shape memory properties with high‐shape fixity ratio (R_f (S1→S2) is 99.2% and R_f (S2→S3) is 99.3%) and shape recovery ratio (R_r (S3→S2) is 92.4% and R_r (S2→S1) is 98.5%).     

Aligned Tubular Conjugated Microporous Polymer Films for the Aggregation‐Induced Emission‐Based Sensing of Explosives

This work shows the sensing performance of conjugated microporous polymer (CMP) tubes. Aligned tubular CMP films (CMP‐AT) are synthesized by a template method. The Sonogashira coupling of tetra(4‐ethynyl)phenylethylene with 1,4‐diiodobenzene in the cylindrical pores of anodic aluminum oxide (AAO) plates and the etching of templates result in the CMP‐AT films. Due to the tetraphenylethylene moieties in the materials, the CMP‐AT films show aggregation‐induced emission (AIE). Based on emission‐quenching behavior, the sensing performance of CMP‐AT films toward model explosives, nitrotoluenes, is studied. The CMP‐AT films having longer CMP tubes with thinner wall thickness show better sensing performance with the Stern–Volmer constant (K_sv) values up to 92 400 M^?1 toward 2,4‐dinitrotoluene. The reduced diffusion pathway of substrates by the thin wall of the CMP tubes is critical for the AIE quenching‐based sensing of nitrotoluenes. These observations indicate that the functionality of CMP materials can be further enhanced by their morphological engineering. Due to the chemical stability of CMP materials, the CMP‐AT‐5 film can be recycled at least five times, maintaining the original sensing performance and tubular morphology.     

Bio‐Inspired Multiple Cycle Healing and Damage Sensing in Elastomer–Magnet Nanocomposites

Damage‐sensing and healing are biological functions which are urgently required in structural health monitoring and remediation of engineering structures. The development of a bio‐inspired multiple cycle damage sensing and triggered healing magnet–polymer nanocomposite (Magpol) is reported. Magpol is comprised of an acrylonitrile butadiene co‐polymer (NBR) matrix and a magnetic nanoparticle (MNP) filler. Magpol nanocomposites in a range of MNP filler concentrations are studied. NBR is selected as the matrix due to its extensive use in industrial coatings, for example, in the automotive industry. Mn‐Zn ferrite MNP is chosen due to its appropriate Curie temperature and good specific absorption rate. Exposure of damaged Magpol to a remote external alternating magnetic field results in MNP heating. The MNP heats the surrounding NBR matrix, resulting in triggered healing. Fractured Magpol samples are successfully healed over several cycles. Incorporation of rhodamine b mechano‐chromophore in Magpol results in multicycle damage sensing by photo‐luminescent absorption. Thus, the developed Magpol is attractive for structural health monitoring and remediation application.