Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene (DMD), and is characterized by progressive weakness in skeletal and cardiac muscles. Currently, dilated cardiomyopathy due to cardiac muscle loss is one of the major causes of lethality in late-stage DMD patients. To study the molecular mechanisms underlying dilated cardiomyopathy in DMD heart, we generated cardiomyocytes (CMs) from DMD and healthy control induced pluripotent stem cells (iPSCs). DMD iPSC-derived CMs (iPSC-CMs) displayed dystrophin deficiency, as well as the elevated levels of resting Ca2+, mitochondrial damage and cell apoptosis. Additionally, we found an activated mitochondria-mediated signaling network underlying the enhanced apoptosis in DMD iPSC-CMs. Furthermore, when we treated DMD iPSC-CMs with the membrane sealant Poloxamer 188, it significantly decreased the resting cytosolic Ca2+ level, repressed caspase-3 (CASP3) activation and consequently suppressed apoptosis in DMD iPSC-CMs. Taken together, using DMD patient-derived iPSC-CMs, we established an in vitro model that manifests the major phenotypes of dilated cardiomyopathy in DMD patients, and uncovered a potential new disease mechanism. Our model could be used for the mechanistic study of human muscular dystrophy, as well as future preclinical testing of novel therapeutic compounds for dilated cardiomyopathy in DMD patients.

Herein, a ternary boron-oxygen-nitrogen embedded polycyclic aromatic hydrocarbon with multiple resonance thermally activated delayed fluorescence (MR-TADF), namely DBNO, is developed by adopting the para boron-πboron and para oxygen-π-oxygen strategy. The designed molecule presents a vivid green emission with a high photoluminescence quantum yield (96 %) and an extremely narrow full width at half maximum (FWHM) of 19 nm/ 0.09 eV, which surpasses all previously reported green TADF emitters to date. In addition, the long molecular structure along the transition dipole moment direction endows it with a high horizontal emitting dipole ratio of 96 %. The organic light-emitting diode (OLED) based on DBNO reveals a narrowband green emission with a peak at 504 nm and a FWHM of 24 nm/0.12 eV. Particularly, a significantly improved device performance is achieved by the TADFsensitization (hyperfluorescence) mechanism, presenting a FWHM of 27 nm and a maximum external quantum efficiency (EQE) of 37.1 %.

How to develop efficient red-emitting organometallics of earth-abundant copper­(I) is a formidable challenge in the field of organic light-emitting diodes (OLEDs) because Cu­(I) complexes have weak spin-orbit coupling and a serious excited-state reorganization effect. Here, a red Cu­(I) complex, MAC*-Cu-DPAC, was developed using a rigid 9,9-diphenyl-9,10-dihydroacridine donor ligand in a carbene-metal-amide motif. The Cu­(I) complex achieved satisfactory red emission, a high photoluminescence quantum yield of up to 70%, and a sub-microsecond lifetime. Thanks to a linear geometry and the acceptor and donor ligands in a coplanar conformation, the complex exhibited a high horizontal dipole ratio of 77% in the host matrix, first demonstrated for coinage metal­(I) complexes. The resulting OLEDs delivered high external quantum efficiencies of 21.1% at a maximum and 20.1% at 1000 nits, together with a red emission peak at ∼630 nm. These values represent the state-of-the-art performance for red-emitting OLEDs based on coinage metal complexes.

Scheme 1. Molecular design strategy for narrowband emission circularly polarized thermally activated delayed fluorescence (CP-TADF) emitters.

Organic light-emitting diodes (OLEDs) have had commercial success in displays and lighting. Compared to red and green OLEDs, blue OLEDs are still the bottleneck because the high-energy and long-lived triplet exciton in traditional blue OLEDs causes the short operational lifetime of the device. As a new type emitter, lanthanide complexes with a 5d–4f transition could have short excited-state lifetimes on the order of nanoseconds. To achieve a high-efficiency 5d–4f transition, we systematically tuned the steric and electronic effects of tripodal tris­(pyrazolyl)­borate ligands and drew a full picture of their Ce­(III) complexes. Intriguingly, all of these complexes show bright blue emission with high photoluminescence quantum yields exceeding 95% and short decay lifetimes of 35–73 ns both in the solid powder and in dichloromethane solutions. Using the Ce­(III) complex emitter, we show a blue OLED with a maximum external quantum efficiency of 14.1% and a maximum luminance of 33,160 cd m–2, and the specific electroluminescence mechanism of direct exciton formation on the Ce­(III) ion with a near-unity exciton utilization efficiency is also confirmed. The discovered photoluminescence and electroluminescence property–structure relationships may shed new light on the rational design of highly efficient lanthanide-based blue emitters and their optoelectronic devices such as OLEDs.

DNA damage accumulates with age (Lombard et al., 2005). However, whether and how robust DNA repair machinery promotes longevity is elusive. Here, we demonstrate that ATM-centered DNA damage response (DDR) progressively declines with senescence and age, while low dose of chloroquine (CQ) activates ATM, promotes DNA damage clearance, rescues age-related metabolic shift, and prolongs replicative lifespan. Molecularly, ATM phosphorylates SIRT6 deacetylase and thus prevents MDM2-mediated ubiquitination and proteasomal degradation. Extra copies of Sirt6 extend lifespan in Atm-/- mice, with restored metabolic homeostasis. Moreover, the treatment with CQ remarkably extends lifespan of Caenorhabditis elegans, but not the ATM-1 mutants. In a progeria mouse model with low DNA repair capacity, long-term administration of CQ ameliorates premature aging features and extends lifespan. Thus, our data highlights a pro-longevity role of ATM, for the first time establishing direct causal links between robust DNA repair machinery and longevity, and providing therapeutic strategy for progeria and age-related metabolic diseases.

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