Structure, signal transduction, activation, and inhibition of integrin αIIbß3.

Integrins are heterodimeric receptors comprising α and ß subunits. They are expressed on the cell surface and play key roles in cell adhesion, migration, and growth. Several types of integrins are expressed on the platelets, including αvß3, αIIbß3, α2ß1, α5ß1, and α6ß1. Among these, physically αIIbß3 is exclusively expressed on the platelet surface and their precursor cells, megakaryocytes. αIIbß3 adopts at least three conformations: i) bent-closed, ii) extended-closed, and iii) extended-open. The transition from conformation i) to iii) occurs when αIIbß3 is activated by stimulants. Conformation iii) possesses a high ligand affinity, which triggers integrin clustering and platelet aggregation. Platelets are indispensable for maintaining vascular system integrity and preventing bleeding. However, excessive platelet activation can result in myocardial infarction (MI) and stroke. Therefore, finding a novel strategy to stop bleeding without accelerating the risk of thrombosis is important. Regulation of αIIbß3 activation is vital for this strategy. There are a large number of molecules that facilitate or inhibit αIIbß3 activation. The interference of these molecules can accurately control the balance between hemostasis and thrombosis. This review describes the structure and signal transduction of αIIbß3, summarizes the molecules that directly or indirectly affect integrin αIIbß3 activation, and discusses some novel antiαIIbß3 drugs. This will advance our understanding of the activation of αIIbß3 and its essential role in platelet function and tumor development.

Optimal Deployment Strategy for Reconfigurable Intelligent Surface under LoSD via Joint Active and Passive Beamforming.

A reconfigurable intelligent surface (RIS) is a new and revolutionizing technology to achieve spectrum-efficient (SE) and energy-efficient (EE) wireless networks. In this paper, we study an optimal deployment strategy of RIS in a line-of-sight domain (LoSD) based on an actual deployment scenario, which jointly considers path loss, transmit power and the energy efficiency of the system. Furthermore, we aim to minimize the transmit power via jointly optimizing its transmit beamforming and the reflect phase shifts of RIS, subject to the quality-of-service (QoS) constraint, namely, the signal-to-noise ratio (SNR) constraint at the user. However, this optimization problem is non-convex with intricately coupled variables. To tackle this challenge, we first apply proper transformation on the QoS constraint and then propose an efficient alternating optimization (AO) algorithm. Simulation results demonstrate that compared to a conventional endpoint deployment strategy that simply deploys RIS at the transceiver ends, our proposed LoSD deployment strategy significantly reduces the transmit power by optimizing the available LoS links when a single RIS is relayed. The impact of the number of reflect elements on the system EE is also unveiled.

Integrated Spatial Modulation and STBC-VBLAST Design toward Efficient MIMO Transmission.

In this contribution, the concept of spatial modulation (SM) is firstly integrated into the structure of space-time block codes (STBC)-aided vertical Bell-labs layered space-time (VBLAST) systems, in order to strike a balanced tradeoff among bit error ratio (BER), spectral efficiency and computational complexity. First of all, in order to enhance the BER performance of STBC-VBLAST, we advocate an effective transmit power allocation (TPA) scheme with negligible implementation costs, while dividing the STBC and VBLAST layers with alleviated interference, so as to facilitate combination with SM. Then, we further utilize the unique structure of SM for enhancing the spectral efficiency of original STBC-VBLAST, wherein the information is conveyed by not only the amplitude/phase modulation (APM) symbols but also the antenna indices. In addition, constellation sets of STBC symbols are specifically designed to be rotated to make full use of the degrees of freedom. Finally, the performance advantages of the above-mentioned structures over traditional STBC-VBLAST are demonstrated by the theoretical derivation of a closed-form expression for the union bound on the bit error probability for various spectral efficiencies, and they are supported by simulation results.

Changes in inflammatory responses and autophagy during apheresis platelet preservation and their correlation with platelet transfusion refractoriness in patients with acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is a common hematopoietic malignancy, and platelet transfusion plays a crucial role in its treatment. This study aimed to investigate the changes in inflammatory response and autophagy during the preservation of apheresis platelets (AP) and their correlation with platelet transfusion refractoriness (PTR) in ALL. ALL patients were included, and APs were categorized based on the preservation period (day 0, day 1, days 2-3, and days 4-5). The activation factors procaspase-activating compound 1 (PAC-1) and P-selectin (CD62P), AP aggregation function, inflammation levels (interleukin 1 beta [IL-1ß], interleukin 6 [IL-6], tumor necrosis factor alpha [TNF-α] and NOD-like receptor thermal protein domain associated protein 3 [NLRP3]), and autophagy-related genes (p62) during AP preservation were assessed. Following co-culturing APs with peripheral blood mononuclear cells (PBMCs), specific activation markers were studied to observe APs influence on immune cells activation. The effectiveness of platelet transfusion was assessed, and risk factors for PTR were analyzed. As the storage duration of AP increased, the activation factors, coagulation factor activity, inflammation levels, and the activation of immune cells in AP increased, while fibrinogen levels and AP aggregation function decreased. The expression levels of autophagy-related genes (the autophagy marker light chain 3B gene [LC3B] and Beclin 1 gene) decreased with prolongation preservation. The effective rate of AP transfusion in ALL patients was 68.21%. AP preservation time, IL-6, p62, and Beclin 1 were identified as independent risk factors affecting PTR in ALL patients. In conclusion, during AP preservation, inflammation, autophagy, and activation of immune cells were observed to increase. AP preservation time, IL-6, p62, and Beclin 1 were independent risk factors for PTR.

Induction of autophagy and autophagy-dependent apoptosis in diffuse large B-cell lymphoma by a new antimalarial artemisinin derivative, SM1044.

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. R-CHOP is currently the standard therapy for DLBCL, but the prognosis of refractory or recurrent patients remains poor. In this study, we synthesized a new water-soluble antimalarial drug artemisinin derivative, SM1044. The treatment of DLBCL cell lines with SM1044 induces autophagy-dependent apoptosis, which is directed by an accelerated degradation of the antiapoptosis protein Survivin, via its acetylation-dependent interaction with the autophagy-related protein LC3-II. Additionally, SM1044 also stimulates the de novo synthesis of ceramide, which in turn activates the CaMKK2-AMPK-ULK1 axis, leading to the initiation of autophagy. Our findings not only elucidate the mechanism of autophagy-dependent apoptosis in DLBCL cells, but also suggest that SM1044 is a promising therapeutic molecule for the treatment of DLBCL, along with R-CHOP regimen.