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Joint endoprosthetics is one of the most successful surgical-orthopedic procedures worldwide, enabling pain reduction and complete restoration of mobility. In the Federal Republic of Germany, around 400,000 joint endoprostheses, hip and knee joints are currently implanted every year ( https://www.eprd.

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During normal cellular homeostasis, unfolded and mislocalized proteins are recognized and removed, preventing the build-up of toxic byproducts. When protein homeostasis is perturbed during ageing, neurodegeneration or cellular stress, proteins can accumulate several forms of chemical damage through reactive metabolites. Such modifications have been proposed to trigger the selective removal of chemically marked proteins; however, identifying modifications that are sufficient to induce protein degradation has remained challenging.

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The Shab family potassium channels are highly enriched at the presynaptic terminals of human neurons.

J Biol Chem

January 2025

Biochemistry & Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA; Molecular, Cellular & Integrated Neurosciences, Colorado State University, Fort Collins, CO 80523, USA; Cell & Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA. Electronic address:

The Shab family voltage-gated K channels (i.e., Kv2.

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Synthesis and biological evaluation of new dual APN/NEP inhibitors as potent analgesics.

Bioorg Chem

January 2025

School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China. Electronic address:

An alternative approach for the management of acute and chronic pains involves prolonging the half-life of endogenous opiates, such as enkephalins that are released in response to nociceptive stimuli. This can be achieved through the inhibition of enzymatic pathways responsible for the hydrolysis of these peptides, particularly targeting Aminopeptidase N (APN) and Neutral Endopeptidase (NEP). In this study, we designed and synthesized a series of dual enkephalinase inhibitors (DENKIs) targeting both APN and NEP as novel analgesic treatments.

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Proximity Ligation Assay to Study Oncogene-Derived Transcription-Replication Conflicts.

J Vis Exp

January 2025

Institute of Biochemistry and Molecular Biology, Hengyang Medical School, University of South China; National Health Commission Key Laboratory of Birth Defect Research and Preventio, Hunan Provincial Maternal and Child Health Care Hospital;

Both DNA replication and RNA transcription utilize genomic DNA as their template, necessitating spatial and temporal separation of these processes. Conflicts between the replication and transcription machinery, termed transcription-replication conflicts (TRCs), pose a considerable risk to genome stability, a critical factor in cancer development. While several factors regulating these collisions have been identified, pinpointing primary causes remains difficult due to limited tools for direct visualization and clear interpretation.

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