Using Cryo-Et to Distinguish Platelets During Pre-acute Myeloid Leukemia From Steady State Hematopoiesis

Early diagnosis of acute myeloid leukemia (AML) in the pre-leukemic stage remains a clinical challenge, as pre-leukemic patients show no symptoms, lacking any known morphological or numerical abnormalities in blood cells. Here, we demonstrate that platelets with structurally abnormal mitochondria emerge at the pre-leukemic phase of AML, preceding detectable changes in blood cell counts or detection of leukemic blasts in blood. We visualized frozen-hydrated platelets from mice at different time points during AML development in situ using electron cryo-tomography (cryo-ET) and identified intracellular organelles through an unbiased semi-automatic process followed by quantitative measurement. A large proportion of platelets exhibited changes in the overall shape and depletion of organelles in AML. Notably, 23% of platelets in pre-leukemic cells exhibit abnormal, round mitochondria with unfolded cristae, accompanied by a significant drop in ATP levels and altered expression of metabolism-related gene signatures. Our study demonstrates that detectable structural changes in pre-leukemic platelets may serve as a biomarker for the early diagnosis of AML

Identification and validation of a platelet-related signature for predicting survival and drug sensitivity in multiple myeloma

Background: Significant progress has been achieved in the management of multiple myeloma (MM) by implementing high-dose therapy and stem cell transplantation. Moreover, the prognosis of patients has been enhanced due to the introduction of novel immunomodulatory drugs and the emergence of new targeted therapies. However, predicting the survival rates of patients with multiple myeloma is still tricky. According to recent researches, platelets have a significant impact in affecting the biological activity of tumors and are essential parts of the tumor microenvironment. Nonetheless, it is still unclear how platelet-related genes (PRGs) connect to the prognosis of multiple myeloma.Methods: We analyzed the expression of platelet-related genes and their prognostic value in multiple myeloma patients in this study. We also created a nomogram combining clinical metrics. Furthermore, we investigated disparities in the biological characteristics, immunological microenvironment, and reaction to immunotherapy, along with analyzing the drug susceptibility within diverse risk groups.Results: By using the platelet-related risk model, we were able to predict patients’ prognosis more accurately. Subjects in the high-risk cohort exhibited inferior survival outcomes, both in the training and validation datasets, as compared to those in the low-risk cohort (p < 0.05). Moreover, there were differences in the immunological microenvironments, biological processes, clinical features, and chemotherapeutic drug sensitivity between the groups at high and low risk. Using multivariable Cox regression analyses, platelet-related risk score was shown to be an independent prognostic influence in MM (p < 0.001, hazard ratio (HR) = 2.001%, 95% confidence interval (CI): 1.467–2.730). Furthermore, the capacity to predict survival was further improved when a combined nomogram was utilized. In training cohort, this outperformed the predictive value of International staging system (ISS) alone from a 5-years area under curve (AUC) = 0.668 (95% CI: 0.611–0.725) to an AUC = 0.721 (95% CI: 0.665–0.778).Conclusion: Our study revealed the potential benefits of PRGs in terms of survival prognosis of MM patients. Furthermore, we verified its potential as a drug target for MM patients. These findings open up novel possibilities for prognostic evaluation and treatment choices for MM

Investigation of Pre-Aged Hardening Single-Point Incremental Forming Process and Mechanical Properties of AA6061 Aluminum Alloy

Currently, the single-point incremental forming process often faces issues such as insufficient formability of the sheet metal and low strength of the formed parts. To address this problem, this study proposes a pre-aged hardening single-point incremental forming (PH-SPIF) process that offers several notable benefits, including shortened procedures, reduced energy consumption, and increased sheet forming limits while maintaining high mechanical properties and geometric accuracy in formed components. To investigate forming limits, an Al-Mg-Si alloy was used to form different wall angles during the PH-SPIF process. Differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) analyses were conducted to characterize microstructure evolution during the PH-SPIF process. The results demonstrate that the PH-SPIF process can achieve a forming limit angle of up to 62°, with excellent geometric accuracy, and hardened component hardness reaching up to 128.5 HV, surpassing the strength of the AA6061-T6 alloy. The DSC and TEM analyses reveal numerous pre-existing thermostable GP zones in the pre-aged hardening alloys, which undergo transformation into dispersed β” phases during the forming procedure, leading to the entanglement of numerous dislocations. The dual effects of phase transformation and plastic deformation during the PH-SPIF process significantly contribute to the desirable mechanical properties of the formed components

Synthesis and rheological performance of shear-thickening waterborne polyurethane

Shear-thickening fluids (STFs) are a new type of intelligent material with excellent performance whose viscosity increase sharply with the increase of shear rate or shear stress. However, the synthesis yield of dispersed phase particles is low, and the particle re-dispersion process is challenging for the industrial production of STFs. In this work, through structural design, a waterborne polyurethane (WPU) with typical shear-thickening properties was synthesized for the first time. This synthesis process is conducive to industrial production. The rheological properties of the synthesized WPU at different concentrations, temperatures, and pH were studied using a rheometer. The results showed that the WPU exhibited typical shear-thickening behavior. However, due to the special core–shell structure of the WPU particles, the shear rate has two transition responses to the shear-thickening behavior. With increasing concentration, the shear-thickening performance of the WPU is enhanced, and the critical shear rate is decreased. For the coexistence of Brownian motion and solvation, the rheological curve of the WPU exhibits a complex response to temperature increase; its shear-thickening behavior decreases with rising temperature, but the viscosity first decreases and then increases with temperature. Due to the presence of carboxyl groups on the surface of the WPU particles, its shear-thickening performance shows a strong response to pH. By appropriately adjusting the pH, the viscosity and particle size of the WPU can be increased through the ionization of carboxyl groups, thereby enhancing the shear-thickening behavior