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A facultative plasminogen-independent thrombolytic enzyme from Sipunculus nudus
Abstract Current thrombolytic therapies primarily function by converting plasminogen into plasmin, a process dependent on the fibrin–activator complex. This dependence, coupled with the substantial molecular size of plasmin, constrains its effectiveness in degrading D-dimer and restricts its diffusion within thrombi. Here, we introduce a small facultative plasminogen-independent thrombolytic enzyme, snFPITE, isolated from Sipunculus nudus . Compared to traditional thrombolytic agents, snFPITE does not require plasminogen for thrombolysis, although its presence enhances lytic activity. This enzyme fully degrades cross-linked fibrin without leaving residual nondegradable D-dimer and generates a smaller fibrinolytic-active agent from plasminogen. A series of male rats and mice models further confirm that snFPITE is a safety injectable thrombolytic agent. Mechanistically, snFPITE activates plasminogen and degrades fibrin(ogen) in a multisite cleavage manner. snFPITE is inhibited by plasminogen activator inhibitor 1 and α2-antiplasmin via a competitive inhibition. We further identify 28 snFPITE candidate sequences, of which 10 are confirmed as functional genes.
Brensocatib in Bronchiectasis — A New Sheriff in Town?
Q&A Europa Clipper mission
Clearing the Smoke on Fossil Fuels — The Health Imperative for a Countermarketing Campaign
Daily briefing: Ancient Phoenicians spread their culture — but not their DNA
Dihydroartemisinic acid dehydrogenase-mediated alternative route for artemisinin biosynthesis
Case 12-2025: A 56-Year-Old Woman with Sore Throat and Rash
Radiation-hardened dendritic-like nanocomposite films with ultrahigh capacitive energy density
Clonal Hematopoiesis as a Driver of Solid Tumors
Parkinson’s gut-microbiota links raise treatment possibilities
Active energy compression of a laser-plasma electron beam
Abstract Radio-frequency (RF) accelerators providing high-quality relativistic electron beams are an important resource enabling many areas of science, as well as industrial and medical applications. Two decades ago, laser-plasma accelerators1 that support orders of magnitude higher electric fields than those provided by modern RF cavities produced quasi-monoenergetic electron beams for the first time2–4. Since then, high-brightness electron beams at gigaelectronvolt (GeV) beam energy and competitive beam properties have been demonstrated from only centimetre-long plasmas5–9, a substantial advantage over the hundreds of metres required by RF-cavity-based accelerators. However, despite the considerable progress, the comparably large energy spread and the fluctuation (jitter) in beam energy still effectively prevent laser-plasma accelerators from driving real-world applications. Here we report the generation of a laser-plasma electron beam using active energy compression, resulting in a performance so far only associated with modern RF-based accelerators. Using a magnetic chicane, the electron bunch is first stretched longitudinally to imprint an energy correlation, which is then removed with an active RF cavity. The resulting energy spread and energy jitter are reduced by more than an order of magnitude to below the permille level, meeting the acceptance criteria of a modern synchrotron, thereby opening the path to a compact storage ring injector and other applications.
Chemical imaging delineates Aβ plaque polymorphism across the Alzheimer’s disease spectrum
Abstract Amyloid-beta (Aβ) plaque formation in Alzheimer’s disease (AD) pathology is morphologically diverse. Understanding the association of polymorphic Aβ pathology with AD pathogenesis and progression is critical in light of emerging Aβ-targeting therapies. In this work, functional amyloid microscopy enhanced by deep learning was integrated with mass spectrometry imaging to delineate polymorphic plaques and to identify their associated Aβ make-up. In both sporadic AD (n = 12) and familial AD (n = 6), dense-core plaques showed higher levels of Aβ1-40 and N-terminal pyroglutamated Aβx-42 compared to diffuse plaques and plaques in non-demented, amyloid positive individuals (n = 5). Notably, a distinct dense-core plaque subtype, coarse-grained plaque, was observed in AD but not in non-demented, amyloid positive patients. Coarse-grained plaques were more abundant in early onset AD, showed increased neuritic dystrophy and higher levels of Aβ1-40 and Aβ3pE-40, an Aβ-pattern similar to cerebral amyloid angiopathy. The correlative chemical imaging paradigm presented here allowed to link structural and biochemical characteristics of Aβ plaque polymorphism across various AD etiologies.