Cardiac-targeted delivery of a novel Drp1 inhibitor for acute cardioprotection.

Dynamin-related protein 1 (Drp1) is a mitochondrial fission protein and a viable target for cardioprotection against myocardial ischaemia-reperfusion injury. Here, we reported a novel Drp1 inhibitor (DRP1i1), delivered using a cardiac-targeted nanoparticle drug delivery system, as a more effective approach for achieving acute cardioprotection. DRP1i1 was encapsulated in cubosome nanoparticles with conjugated cardiac-homing peptides (NanoDRP1i1) and the encapsulation efficiency was 99.

An optimized plasmalogen modulating dietary supplement provides greater protection in a male than female mouse model of dilated cardiomyopathy.

We previously reported that plasmalogens, a class of phospholipids, were decreased in a setting of dilated cardiomyopathy (DCM). Plasmalogen levels can be modulated via a dietary supplement called alkylglycerols (AG) which has demonstrated benefits in some disease settings. However, its therapeutic potential in DCM remained unknown.

α-Ketoglutarate dehydrogenase is a therapeutic vulnerability in acute myeloid leukemia.

Perturbations in intermediary metabolism contribute to the pathogenesis of acute myeloid leukemia (AML) and can produce therapeutically actionable dependencies. Here, we probed whether alpha-ketoglutarate (aKG) metabolism represents a specific vulnerability in AML. Using functional genomics, metabolomics, and mouse models, we identified the aKG dehydrogenase complex, which catalyzes the conversion of aKG to succinyl CoA, as a molecular dependency across multiple models of adverse-risk AML.

Unraveling the Origin of Unusual Cs Atom Disorder in Cesium Octahedral Molybdenum Halide Cluster Compounds, Cs[{MoX}X] (X = Cl and Br).

In this study, we investigate structural disorder and its implications in metal cluster (MC)-based compounds, specifically focusing on Cs[{MoX}X] (X = Cl and Br). Utilizing synchrotron radiation X-ray diffraction, Fourier transform infrared spectroscopy, and luminescence measurements, we examined the incorporation of water molecules into these compounds and their effects on the crystal structure and optical properties. Our findings reveal that the presence of water molecules induces the lattice disorder, particularly the displacement of Cs atoms.

Incorporating Economic Evidence in Clinical Guidelines: A Framework From the Clinical Guidelines Committee of the American College of Physicians.

In recognition of accelerating health care spending and alignment with the American College of Physicians (ACP) principles of promoting high-value care, the ACP Clinical Guidelines Committee (CGC) developed a framework to standardize its approach to identifying, appraising, and considering economic evidence in the development of ACP clinical guidelines. This article presents the CGC's process for incorporating economic evidence, which encompasses cost-effectiveness analyses, economic outcomes in randomized controlled trials, and resource utilization (intervention cost) data. Economic evidence is one component of ACP recommendations.