Nonsense mutations promote premature translational termination and cause anywhere from 5-70% of the individual cases of most inherited diseases. Studies on nonsense-mediated cystic fibrosis have indicated that boosting specific protein synthesis from <1% to as little as 5% of normal levels may greatly reduce the severity or eliminate the principal manifestations of disease. To address the need for a drug capable of suppressing premature termination, we identified PTC124-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons. PTC124 activity, optimized using nonsense-containing reporters, promoted dystrophin production in primary muscle cells from humans and mdx mice expressing dystrophin nonsense alleles, and rescued striated muscle function in mdx mice within 2-8 weeks of drug exposure. PTC124 was well tolerated in animals at plasma exposures substantially in excess of those required for nonsense suppression. The selectivity of PTC124 for premature termination codons, its well characterized activity profile, oral bioavailability and pharmacological properties indicate that this drug may have broad clinical potential for the treatment of a large group of genetic disorders with limited or no therapeutic options.

Spinal muscular atrophy (SMA) is a genetic disease caused by mutation or deletion of the survival of motor neuron 1 (SMN1) gene. A paralogous gene in humans, SMN2, produces low, insufficient levels of functional SMN protein due to alternative splicing that truncates the transcript. The decreased levels of SMN protein lead to progressive neuromuscular degeneration and high rates of mortality. Through chemical screening and optimization, we identified orally available small molecules that shift the balance of SMN2 splicing toward the production of full-length SMN2 messenger RNA with high selectivity. Administration of these compounds to Δ7 mice, a model of severe SMA, led to an increase in SMN protein levels, improvement of motor function, and protection of the neuromuscular circuit. These compounds also extended the life span of the mice. Selective SMN2 splicing modifiers may have therapeutic potential for patients with SMA.

A novel type of polymer nanocomposite (NC) hydrogel with extraordinary mechanical properties at low inorganic content is prepared and investigated. The NC hydrogels consist of isethionate-loaded layered double hydroxide/polyacrylamide (LDH-Ise/PAM) - with LDH-Ise being used because of its swelling properties - and no conventional organic crosslinker. The NC hydrogels exhibit an unusual hierarchical porous structure at the micro- and nanometer scales, and their elongation at break can exceed 4000%.

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In this review, recent advances in organic polymer thermoelectric composites, mainly focusing on the preparation strategies to achieve enhanced thermoelectric performance, have been discussed.

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The urgent need for consistent, reliable, ecofriendly, and stable power sources drives the development of new green energy materials. Thermoelectric (TE) materials receive increasing attention due to their unique capability of realizing the direct energy conversion between heat and electricity, showing diverse applications in harvesting waste heat and low‐grade heat. Carbon materials such as carbon nanotubes (CNTs) and graphene have experienced a rapid development as TE materials because of their intrinsic ultrahigh electrical conductivity and light weight. Besides, polymer‐based carbon composites are particularly fascinating as the combination of the merits of polymers and filler materials leads to high TE performance and superior flexibility. Herein, the recent TE advances are systematically summarized in the studied popularity of carbon materials (ie, CNTs and graphene) and the category of polymers. The conducting polymer‐based carbon materials are particularly highlighted. Finally, the remaining challenges and some tentative suggestions possibly guiding future developments are proposed, which may pave a way for a bright future of carbon and carbon composites in the energy market.