Fluorescence imaging in the second near-infrared window (NIR-II) allows visualization of deep anatomical features with an unprecedented degree of clarity. NIR-II fluorophores draw from a broad spectrum of materials spanning semiconducting nanomaterials to organic molecular dyes, yet unfortunately all water-soluble organic molecules with >1,000 nm emission suffer from low quantum yields that have limited temporal resolution and penetration depth. Here, we report tailoring the supramolecular assemblies of protein complexes with a sulfonated NIR-II organic dye (CH-4T) to produce a brilliant 110-fold increase in fluorescence, resulting in the highest quantum yield molecular fluorophore thus far. The bright molecular complex allowed for the fastest video-rate imaging in the second NIR window with ∼50-fold reduced exposure times at a fast 50 frames-per-second (FPS) capable of resolving mouse cardiac cycles. In addition, we demonstrate that the NIR-II molecular complexes are superior to clinically approved ICG for lymph node imaging deep within the mouse body.
Integrins are a family of transmembrane glycoprotein signaling receptors that can transmit bioinformation bidirectionally across the plasma membrane. Integrin αIIbβ3 is expressed at a high level in platelets and their progenitors, where it plays a central role in platelet functions, hemostasis, and arterial thrombosis. Integrin αIIbβ3 also participates in cancer progression, such as tumor cell proliferation and metastasis. In resting platelets, integrin αIIbβ3 adopts an inactive conformation. Upon agonist stimulation, the transduction of inside-out signals leads integrin αIIbβ3 to switch from a low-to high-affinity state for fibrinogen and other ligands. Ligand binding causes integrin clustering and subsequently promotes outside-in signaling, which initiates and amplifies a range of cellular events to drive essential platelet functions such as spreading, aggregation, clot retraction, and thrombus consolidation. Regulation of the bidirectional signaling of integrin αIIbβ3 requires the involvement of numerous interacting proteins, which associate with the cytoplasmic tails of αIIbβ3 in particular. Integrin αIIbβ3 and its signaling pathways are considered promising targets for antithrombotic therapy. This review describes the bidirectional signal transduction of integrin αIIbβ3 in platelets, as well as the proteins responsible for its regulation and therapeutic agents that target integrin αIIbβ3 and its signaling pathways.
Background: The patellar tendon is often considered the “gold standard” graft for reducing the risk of graft rupture after anterior cruciate ligament (ACL) reconstruction. However, its use may also be associated with an increased risk of injury to the contralateral ACL. Purpose: To clarify the association between graft choice and the risk of revision and contralateral ACL reconstruction. Study Design: Cohort study; Level of evidence, 2. Methods: Prospective data captured by the New Zealand ACL Registry between April 2014 and December 2018 were reviewed. All primary ACL reconstructions performed using either a hamstring tendon or patellar tendon autograft were included. Cox regression survival analysis adjusting for patient factors was performed to compare the risk of revision and contralateral ACL reconstruction between the hamstring tendon graft and the patellar tendon graft. Results: A total of 7155 primary ACL reconstructions were reviewed, of which 5563 (77.7%) were performed using a hamstring tendon graft and 1592 (22.3%) were performed using a patellar tendon graft. Patients with a hamstring tendon graft had a revision rate of 2.7% compared with 1.3% in patients with a patellar tendon graft (adjusted hazard ratio [HR], 2.51; 95% CI, 1.55-4.06; P < .001). The patellar tendon graft was associated with an increased risk of contralateral ACL reconstruction compared with the hamstring tendon graft (adjusted HR, 1.91; 95% CI, 1.15-3.16; P = .012). The number needed to treat (NNT) with a patellar tendon graft to prevent 1 revision was 73.6. However, the NNT with a hamstring tendon graft to prevent 1 contralateral reconstruction was 116.3. Conclusion: Use of a patellar tendon graft reduced the risk of graft rupture but was associated with an increased risk of injury to the contralateral ACL. Adequate rehabilitation and informed decision making on return to activity and injury prevention measures may be important in preventing subsequent injury to the healthy knee.
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