The overproduction of reactive oxygen species (ROS) generates oxidative stress in cells. Oxidative stress results in various pathophysiological conditions, especially cancers and neurodegenerative diseases (NDD). The Keap1-Nrf2 [Kelch-like ECH-associated protein 1-nuclear factor (erythroid-derived 2)-like 2] regulatory pathway plays a central role in protecting cells against oxidative and xenobiotic stresses. The Nrf2 transcription factor activates the transcription of several cytoprotective genes that have been implicated in protection from cancer and NDD. The Keap1-Nrf2 system acts as a double-edged sword: Nrf2 activity protects cells and makes the cell resistant to oxidative and electrophilic stresses, whereas elevated Nrf2 activity helps in cancer cell survival and proliferation. Several groups in the recent past, from both academics and industry, have reported the potential role of Nrf2-mediated transcription to protect from cancer and NDD, resulting from mechanisms involving xenobiotic and oxidative stress. It suggests that the Keap1-Nrf2 system is a potential therapeutic target to combat cancer and NDD by designing and developing modulators (inhibitors/activators) for Nrf2 activation. Herein, we review and discuss the recent advancement in the regulation of the Keap1-Nrf2 system, its role under physiological and pathophysiological conditions including cancer and NDD, and modulators design strategies for Nrf2 activation.

Here we report a modular strategy for preparing physically cross-linked and mechanically robust free-standing hydrogels comprising unique thermotropic liquid crystalline (LC) domains and magnetic nanoparticles both of which serve as the physical cross-linkers resulting in hydrogels that can be used as magnetically responsive soft actuators. A series of amphiphilic LC pentablock copolymers of poly(acrylic acid) (PAA), poly(5-cholesteryloxypentyl methacrylate) (PC5MA), and poly(ethylene oxide) (PEO) blocks in the sequence of PAA-PC5MA-PEO-PC5MA-PAA were prepared using reversible addition-fragmentation chain transfer polymerization. These pentablock copolymers served as macromolecular ligands to template Fe(3)O(4) magnetic nanoparticles (MNPs), which were directly anchored to the polymer chains through the coordination bonds with the carboxyl groups of PAA blocks. The resulting polymer/MNP nanocomposites comprised a complicated hierarchical structure in which polymer-coated MNP clusters were dispersed in a microsegregated pentablock copolymer matrix that further contained LC ordering. Upon swelling, the hierarchical structure was disrupted and converted to a network structure, in which MNP clusters were anchored to the polymer chains and LC domains stayed intact to connect solvated PEO and PAA blocks, leading to a free-standing LC magnetic hydrogel (LC ferrogel). By varying the PAA weight fraction (f(AA)) in the pentablock copolymers, the swelling degrees (Q) of the resulting LC ferrogels were tailored. Rheological experiments showed that these physically cross-linked free-standing LC ferrogels exhibit good mechanical strength with storage moduli G' of around 10(4)-10(5) Pa, similar to that of natural tissues. Furthermore, application of a magnetic field induced bending actuation of the LC ferrogels. Therefore, these physically cross-linked and mechanically robust LC ferrogels can be used as soft actuators and artificial muscles. Moreover, this design strategy is a versatile platform for incorporation of different types of nanoparticles (metallic, inorganic, biological, etc.) into multifunctional amphiphilic block copolymers, resulting in unique free-standing hybrid hydrogels of good mechanical strength and integrity with tailored properties and end applications.

We report synthesis and characterization of a new class of side-chain liquid crystalline random terpolymers (SCLCP), its cross-linked network (SCLCN), and the corresponding shape memory properties. The SCLCP comprising three monomers, 5-{15-(cholesteryloxycarbonyl)-pentadecyloxycarbonyl}-bicyclo[2.2.1]hept-2-ene (NBCh15), 5-(acryloyl butoxycarbonyl)-bicyclo[2.2.1]hept-2-ene (NBBA), and poly(ethylene glycol) functionalized norbornene (NBPEG), is synthesized by ring-opening metathesis polymerization (ROMP) using Grubbs catalyst second generation, resulting in a random terpolymer. Each monomer provides a specific function in the terpolymer: (1) NBCh15 affords liquid crystalline properties, (2) NBBA is a cross-linkable unit, and (3) NBPEG acts as an internal plasticizer. The mesomorphic structure of the terpolymer investigated by X-ray diffraction (XRD) exhibits highly interdigitated smectic A (SmA) mesophase comprising cholesteryl ester mesogens. The acrylate end group in the NBBA undergoes cross-linking by curing at 120 °C, resulting in the SCLCN. Optimal cross-linking conditions are determined by monitoring gel fraction produced from different curing times. Thermal transitions including glass transition temperature (T g) and clearing temperature (T cl) before and after cross-linking are analyzed by differential scanning calorimetry (DSC). Linear viscoelastic properties of the SCLCN reveal three different relaxations associated with dynamic soft elasticity as well as T g and T cl. One-way shape memory cycles (1W-SMCs) of the SCLCN are programmed using (1) T g, (2) T cl, and (3) combined (T g and T cl) as a shape memory transition temperature (T trans). The T g-based SMCs exhibits excellent shape fixing (>97%) and shape recovery ratio (>96%) with large strain (>150%). In the T cl-based SMCs, the cooling induced elongation of strain is observed due to the development of interdigitated SmA mesophase. The shape fixing by interdigitated SmA is achieved during the T cl-based SMCs unlike conventional shape fixing methods such as vitrification or crystallization. If both T g and T cl serve as T trans for SMCs, the permanent shape is restored by two stages of shape recovery around T g and T cl. The dual T trans (T g and T cl) inherent in this SCLCN allows for creating different types of SMCs and for the memorization of shape at two different temperature windows, thereby, programmed shapes by different mechanism would be recovered in a more precise manner.

Herein, we investigate the influence of nanoscale smectic polymorphism within end-on fixed side-chain liquid crystalline polymer networks (SCLCNs) on macroscopic shape-memory and actuation properties. We have synthesized a series of SCLC-type linear (TP-n) and cross-linked random terpolymers (XL-TP-n) with varying length of flexible methylene spacers (n = 5, 10, and 15) between polynorbornene main-chain and cholesteryl ester side-chains. Thermal and mechanical analyses by differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) confirm a glass transition (T(g)), a clearing temperature (T(cl)), and a network structure in the XL-TP-n. Detailed structural investigation conducted using wide-angle and small-angle X-ray scattering (WAXS and SAXS) at room temperature proves self-assembled smectic A (SmA) polymorphism of the XL-TP-n which evolves from non-interdigitated bilayer (SmA(2)) for n = 5 to mixed layers of monolayer-like highly interdigitated layer (SmA(1)) and SmA(2) for n = 10 and to SmA(1) for n = 15. In addition, TP10 at temperatures above 60 °C interestingly shows transformation of SmA structure from mixed layer (SmA(1) + SmA(2)) to interdigitated structure (SmA(d)). The SmA polymorphism developed in TP-n during shape-memory cycles (SMCs) significantly impacts the ultimate strain responses. A mechanism for the unique interdigitation-based thermostrictive behavior is proposed. More importantly, this new actuation mechanism observed in these XL-TP-n can be exploited to develop intelligent thermal actuators.

We report on the development of a liquid crystalline block copolymer with brush-type architecture as a platform for creating functional materials by magnetic-fielddirected self-assembly. Ring-opening metathesis of n-alkyloxy cyanobiphenyl and polylactide (PLA) functionalized norbornene monomers provides efficient polymerization yielding low polydispersity block copolymers. The mesogenic species, spacer length, monomer functionality, brush-chain length, and overall molecular weight were chosen and optimized to produce hexagonally packed cylindrical PLA domains which self-assemble and align parallel to an applied magnetic field. The PLA domains can be selectively removed by hydrolytic degradation resulting in the production of nanoporous films. The polymers described here provide a versatile platform for scalable fabrication of aligned nanoporous materials and other functional materials based on such templates.

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A scalable approach for developing large area polymer films, with stimuli responsive vertically aligned nanopores is reported. Magnetic fields are used to create highly aligned hexagonally packed block copolymer cylindrical microdomains with order parameters exceeding 0.95. Selective etch removal of material yields nanoporous films which demonstrate reversible pore closure on heating.

Alkene metathesis catalyst development has made significant progress over recent years. Research in metathesis catalyst design has endeavoured to tackle three key issues: those of (i) catalyst efficiency and activity, (ii) substrate scope and selectivity--particularly stereoselective metathesis reactions--and (iii) the minimization of metal impurities and catalyst recycling. This article describes a brief history of metathesis catalyst development, followed by a survey of more recent research, with a particular emphasis on ruthenium catalysts.