Cell-scale hemolysis evaluation of intervenient ventricular assist device based on dissipative particle dynamics

Most of the existing hemolysis mechanism studies are carried out on the macro flow scale. They assume that the erythrocyte membranes with different loads will suffer the same damage, which obviously has limitations. Thus, exploring the hemolysis mechanism through the macroscopic flow field information is a tough challenge. In order to further understand the non-physiological shear hemolysis phenomenon at the cell scale, this study used the coarse-grained erythrocytes damage model at the mesoscopic scale based on the transport dissipative particle dynamics (tDPD) method. Combined with computational fluid dynamics the hemolysis of scalarized shear stress (τ) in the clearance of “Impella 5.0” was evaluated under the Lagrange perspective and Euler perspective. The results from the Lagrange perspective showed that the change rate of scaled shear stress (τ˙) was the most critical factor in damaging RBCs in the rotor region of “Impella 5.0”and other transvalvular micro-axial blood pumps. Then, we propose a dimensionless number Dk with time integration based on τ˙ to evaluate hemolysis. The Dissipative particle dynamics simulation results are consistent with the Dk evaluation results, so τ˙ may be an important factor in the hemolysis of VADs. Finally, we tested the hemolysis of 30% hematocrit whole blood in the “Impella 5.0” shroud clearance from the Euler perspective. Relevant results indicate that because of the wall effect, the RBCs near the impeller side are more prone to damage, and most of the cytoplasm is also gathered at the rotor side

Onset mechanism of an inverted U-shaped solar filament eruption revealed by NVST, SDO, and STEREO-A observations

Utilizing observations from the New Vacuum Solar Telescope (NVST), Solar Dynamics Observatory (SDO), and Solar Terrestrial Relations Observatory-Ahead (STEREO-A), we investigate the event from two distinct observational perspectives: on the solar disk using NVST and SDO, and on the solar limb using STEREO-A. We employ both a non-linear force-free field model and a potential field model to reconstruct the coronal magnetic field, aiming to understand its magnetic properties. Two precursor jet-like activities were observed before the eruption, displaying an untwisted rotation. The second activity released an estimated twist of over two turns. During these two jet-like activities, Y-shaped brightenings, newly emerging magnetic flux accompanied by magnetic cancellation, and the formation of newly moving fibrils were identified. Combining these observational features, it can be inferred that these two precursor jet-like activities released the magnetic field constraining the filament and were triggered by newly emerging magnetic flux. Before the filament eruption, it was observed that some moving flows had been ejected from the site as the onset of two jet-like activities, indicating the same physical process as two jet-like activities. Extrapolations revealed that the filament laid under the height of the decay index of 1.0 and had strong magnetic field (540 Gauss) and a high twisted number (2.4 turns) before the eruption. An apparent rotational motion was observed during the filament eruption. We deduce that the solar filament, exhibiting an inverted U-shape, is a significantly twisted flux rope. The eruption of the filament was initiated by the release of constraining magnetic fields through continuous magnetic reconnection. This reconnection process was triggered by the emergence of newly magnetic flux.Comment: 18 pages, 12 figures, accepted for publication in Astronomy & Astrophysic

SUMOylation patterns and signature characterize the tumor microenvironment and predict prognosis in lung adenocarcinoma

Background: Recent studies have revealed that SUMOylation modifications are involved in various biological processes, including cancer development and progression. However, the precise role of SUMOylation in lung adenocarcinoma (LUAD), especially in the tumor immune microenvironment, is not yet clear.Methods: We identified SUMOylation patterns by unsupervised consensus clustering based on the expression of SUMOylation regulatory genes. The tumor microenvironment in lung adenocarcinoma was analyzed using algorithms such as GSVA and ssGSEA. Key genes of SUMOylation patterns were screened for developing a SUMOylation scoring model to assess immunotherapy and chemotherapy responses in lung adenocarcinoma patients. Experiments were conducted to validate the differential expression of model genes in lung adenocarcinoma. Finally, we constructed a nomogram based on the SUMOylation score to assess the prognosis of individual lung adenocarcinoma patients.Results: Two patterns of SUMOylation were identified, namely, SUMO-C1, which showed anti-tumor immune phenotype, and SUMO-C2, which showed immunosuppressive phenotype. Different genomic subtypes were also identified; subtype gene-T1 exhibited a reciprocal restriction between the immune microenvironment and stromal microenvironment. High SUMOylation scores were indicative of poor lung adenocarcinoma prognosis. SUMOylation score was remarkably negatively correlated with the infiltration of anti-tumor immune cells, and significantly positively correlated with immune cells promoting immune escape and immune suppression. In addition, patients with low scores responded better to immunotherapy. Therefore, the developed nomogram has a high prognostic predictive value.Conclusion: The SUMOylation patterns can well discriminate the tumor microenvironment features of lung adenocarcinoma, especially the immune cell infiltration status. The SUMOylation score can further assess the relationship between SUMOylation and immune cell crosstalk and has significant prognostic value and can be used to predict immunotherapy and chemotherapy response in patients with lung adenocarcinoma

Constraint-Based Modeling and Kinetic Analysis of the Smad Dependent TGF-β Signaling Pathway

Background Investigation of dynamics and regulation of the TGF-β signaling pathway is central to the understanding of complex cellular processes such as growth, apoptosis, and differentiation. In this study, we aim at using systems biology approach to provide dynamic analysis on this pathway. Methodology/Principal Findings We proposed a constraint-based modeling method to build a comprehensive mathematical model for the Smad dependent TGF-β signaling pathway by fitting the experimental data and incorporating the qualitative constraints from the experimental analysis. The performance of the model generated by constraint-based modeling method is significantly improved compared to the model obtained by only fitting the quantitative data. The model agrees well with the experimental analysis of TGF-β pathway, such as the time course of nuclear phosphorylated Smad, the subcellular location of Smad and signal response of Smad phosphorylation to different doses of TGF-β. Conclusions/Significance The simulation results indicate that the signal response to TGF-β is regulated by the balance between clathrin dependent endocytosis and non-clathrin mediated endocytosis. This model is useful to be built upon as new precise experimental data are emerging. The constraint-based modeling method can also be applied to quantitative modeling of other signaling pathways

Polyploidy underlies co-option and diversification of biosynthetic triterpene pathways in the apple tribe

Whole-genome duplication (WGD) plays important roles in plant evolution and function, yet little is known about how WGD underlies metabolic diversification of natural products that bear significant medicinal properties, especially in nonmodel trees. Here, we reveal how WGD laid the foundation for co-option and differentiation of medicinally important ursane triterpene pathway duplicates, generating distinct chemotypes between species and between developmental stages in the apple tribe. After generating chromosome-level assemblies of a widely cultivated loquat variety and Gillenia trifoliata, we define differentially evolved, duplicated gene pathways and date the WGD in the apple tribe at 13.5 to 27.1 Mya, much more recent than previously thought. We then functionally characterize contrasting metabolic pathways responsible for major triterpene biosynthesis in G. trifoliata and loquat, which pre- and postdate the Maleae WGD, respectively. Our work mechanistically details the metabolic diversity that arose post-WGD and provides insights into the genomic basis of medicinal properties of loquat, which has been used in both traditional and modern medicines

Bioinformatic Analysis and Post-Translational Modification Crosstalk Prediction of Lysine Acetylation

Recent proteomics studies suggest high abundance and a much wider role for lysine acetylation (K-Ac) in cellular functions. Nevertheless, cross influence between K-Ac and other post-translational modifications (PTMs) has not been carefully examined. Here, we used a variety of bioinformatics tools to analyze several available K-Ac datasets. Using gene ontology databases, we demonstrate that K-Ac sites are found in all cellular compartments. KEGG analysis indicates that the K-Ac sites are found on proteins responsible for a diverse and wide array of vital cellular functions. Domain structure prediction shows that K-Ac sites are found throughout a wide variety of protein domains, including those in heat shock proteins and those involved in cell cycle functions and DNA repair. Secondary structure prediction proves that K-Ac sites are preferentially found in ordered structures such as alpha helices and beta sheets. Finally, by mutating K-Ac sites in silico and predicting the effect on nearby phosphorylation sites, we demonstrate that the majority of lysine acetylation sites have the potential to impact protein phosphorylation, methylation, and ubiquitination status. Our work validates earlier smaller-scale studies on the acetylome and demonstrates the importance of PTM crosstalk for regulation of cellular function

The ER-membrane transport system is critical for intercellular trafficking of the NSm movement protein and Tomato Spotted Wilt Tospovirus

Plant viruses move through plasmodesmata to infect new cells. The plant endoplasmic reticulum (ER) is interconnected among cells via the ER desmotubule in the plasmodesma across the cell wall, forming a continuous ER network throughout the entire plant. This ER continuity is unique to plants and has been postulated to serve as a platform for the intercellular trafficking of macromolecules. In the present study, the contribution of the plant ER membrane transport system to the intercellular trafficking of the NSm movement protein and Tomato spotted wilt tospovirus (TSWV) is investigated. We showed that TSWV NSm is physically associated with the ER membrane in Nicotiana benthamiana plants. An NSm-GFP fusion protein transiently expressed in single leaf cells was trafficked into neighboring cells. Mutations in NSm that impaired its association with the ER or caused its mis-localization to other subcellular sites inhibited cell-to-cell trafficking. Pharmacological disruption of the ER network severely inhibited NSm-GFP trafficking but not GFP diffusion. In the Arabidopsis thaliana mutant rhd3 with an impaired ER network, NSm-GFP trafficking was significantly reduced, whereas GFP diffusion was not affected. We also showed that the ER-to-Golgi secretion pathway and the cytoskeleton transport systems were not involved in the intercellular trafficking of TSWV NSm. Importantly, TSWV cell-to-cell spread was delayed in the ER-defective rhd3 mutant, and this reduced viral infection was not due to reduced replication. On the basis of robust biochemical, cellular and genetic analysis, we established that the ER membrane transport system serves as an important direct route for intercellular trafficking of NSm and TSWV

An Electrochemical Immunosensor Based on Chitosan–Graphene Nanosheets for Aflatoxin B1 Detection in Corn

We reported a highly efficient electrochemical immunosensor utilizing chitosan–graphene nanosheets (CS-GNs) nanocomposites for the detection of aflatoxin B1 (AFB1) in corn samples. The CS-GNs nanocomposites, serving as a modifying layer, provide a significant specific surface area and biocompatibility, thereby enhancing both the electron transfer rate and the efficiency of antibody immobilization. The electrochemical characterization was conducted utilizing both differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Moreover, the antibody concentration, pH, antibody immobilization time, and immunoreaction time, were optimized. The results showed that the current change (ΔI) before and after the immunoreaction demonstrated a strong linear relationship (R2=0.990) with the AFB1 concentration, as well as good specificity and stability. The linear range extended from 0.05 to 25 ng/mL, with a detection limit of 0.021 ng/mL (S/N=3). The immunosensor exhibited a recovery rate ranging from 97.3% to 101.4% in corn samples, showing a promising performance using an efficient method, and indicating a remarkable prospect for the detection of fungal toxins in grains

Development of a 3-DOF Cylindrical Ultrasonic Motor Based on Non-Standard Modes

Cylindrical multi-degree-of-freedom (multi-DOF) ultrasonic motors have the potential to significantly reduce motor size compared to other ultrasonic motors. They find applications in various systems, including micro-robot joints and space probes. This paper proposes a 3-DOF cylindrical ultrasonic motor with hybrid vibration modes. Hybrid vibration modes encompass non-standard longitudinal and bending vibrations. The structure and operating principle of the motor are described first. COMSOL Multiphysics models the stator’s vibration modes, frequency response, and 3-DOF motion. A motor prototype is manufactured and characterized to demonstrate the output characteristics of the motor. The results indicate that the motor has a no-load speed of 37 rpm along the x- and y-axes and up to 77 rpm along the z-axis. The maximum output torque of the motor is 25 Nm. The motor is low in height and compact, providing a method for further reducing the stator length of motors of the same type

Recruitment of Vps34 PI3K and enrichment of PI3P phosphoinositide in the viral replication compartment is crucial for replication of a positive-strand RNA virus.

Tombusviruses depend on subversions of multiple host factors and retarget cellular pathways to support viral replication. In this work, we demonstrate that tomato bushy stunt virus (TBSV) and the closely-related carnation Italian ringspot virus (CIRV) recruit the cellular Vps34 phosphatidylinositol 3-kinase (PI3K) into the large viral replication compartment. The kinase function of Vps34 is critical for TBSV replication, suggesting that PI(3)P phosphoinositide is utilized by TBSV for building of the replication compartment. We also observed increased expression of Vps34 and the higher abundance of PI(3)P in the presence of the tombusviral replication proteins, which likely leads to more efficient tombusvirus replication. Accordingly, overexpression of PI(3)P phosphatase in yeast or plants inhibited TBSV replication on the peroxisomal membranes and CIRV replication on the mitochondrial membranes. Moreover, the purified PI(3)P phosphatase reduced TBSV replicase assembly in a cell-free system. Detection of PI(3)P with antibody or a bioprobe revealed the enrichment of PI(3)P in the replication compartment. Vps34 is directly recruited into the replication compartment through interaction with p33 replication protein. Gene deletion analysis in surrogate yeast host unraveled that TBSV replication requires the vesicle transport function of Vps34. In the absence of Vps34, TBSV cannot efficiently recruit the Rab5-positive early endosomes, which provide PE-rich membranes for membrane biogenesis of the TBSV replication compartment. We found that Vps34 and PI(3)P needed for the stability of the p33 replication protein, which is degraded by the 26S proteasome when PI(3)P abundance was decreased by an inhibitor of Vps34. In summary, Vps34 and PI(3)P are needed for providing the optimal microenvironment for the replication of the peroxisomal TBSV and the mitochondrial CIRV