Conductive hydrogels are gaining significant attention as promising candidates for the fabrication materials for flexible electronics. Nevertheless, improving the tensile properties, hysteresis, ...durability, adhesion, and electrochemical properties of these hydrogels remains challenging. This work reports the development of a novel semi‐interpenetrating network poly(ionic liquid) hydrogel named PATV, via the in situ polymerization of acrylamide, N‐Tris(hydroxymethyl)methyl acrylamide, and 1‐vinyl‐3‐butylimidazolium tetrafluoroborate. The density functional theory calculations reveal that the poly(ionic liquid) in the hydrogel network acts as physical cross–linking points to construct hydrogen‐bond networks. Furthermore, the hydrogen‐bond networks dissipate energy efficiently and quickly, and thus stress concentration and hysteresis are avoided. The prepared hydrogel has a low hysteresis (9%), high tensile properties (900%), fast response (180 ms), high sensitivity (gauge factor = 10.4, pressure sensitivity = 0.14 kPa−1), and wide sensing range (tensile range: 1–600%, compression range: 0.1–20 kPa). A multifunctional sensor designed based on the designed hydrogel enables real‐time, rapid, and stable response‐ability for the detection of human movement, facial expression recognition, pronunciation, pulse, handwriting, and Morse code encryption. Furthermore, the assembled triboelectric nanogenerator displays an excellent energy harvesting capability, thus highlighting its potential application in self‐powered flexible wearable electronic devices.
A semi‐interpenetrating poly(ionic liquid) network‐driven low hysteresis and transparent hydrogel as a self‐powered multifunctional sensor is reported in this work. The multifunctional sensor enables the real‐time, rapid, and stable response ability of different types of human movement. Furthermore, the assembled triboelectric nanogenerator displays an excellent energy harvesting capability.
Tissue engineering (TE) is an integrated discipline that involves engineering and natural science in the development of biological materials to replace, repair, and improve the function of diseased ...or missing tissues. Traditional medical and surgical treatments have been reported to have side effects on patients caused by organ necrosis and tissue loss. However, engineered tissues and organs provide a new way to cure specific diseases. Scaffold fabrication is an important step in the TE process. This paper summarizes and reviews the widely used scaffold fabrication methods, including conventional methods, electrospinning, three-dimensional printing, and a combination of molding techniques. Furthermore, the differences among the properties of tissues, such as pore size and distribution, porosity, structure, and mechanical properties, are elucidated and critically reviewed. Some studies that combine two or more methods are also reviewed. Finally, this paper provides some guidance and suggestions for the future of scaffold fabrication.
Concomitant inhibition of vascular endothelial growth factor (VEGF) and programmed cell death protein 1 (PD-1) or its ligand PD-L1 is a standard of care for patients with advanced hepatocellular ...carcinoma (HCC), but only a minority of patients respond, and responses are usually transient. Understanding the effects of therapies on the tumor microenvironment (TME) can provide insights into mechanisms of therapeutic resistance.
14 patients with HCC were treated with the combination of cabozantinib and nivolumab through the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center. Among them, 12 patients (5 responders + 7 non-responders) underwent successful margin negative resection and are subjects to tissue microarray (TMA) construction containing 37 representative tumor region cores. Using the TMAs, we performed imaging mass cytometry (IMC) with a panel of 27-cell lineage and functional markers. All multiplexed images were then segmented to generate a single-cell dataset that enables (1) tumor-immune compartment analysis and (2) cell community analysis based on graph-embedding methodology. Results from these hierarchies are merged into response-associated biological process patterns.
Image processing on 37 multiplexed-images discriminated 59,453 cells and was then clustered into 17 cell types. Compartment analysis showed that at immune-tumor boundaries from NR, PD-L1 level on tumor cells is significantly higher than remote regions; however, Granzyme B expression shows the opposite pattern. We also identify that the close proximity of CD8
T cells to arginase 1
(Arg1
) macrophages, rather than CD4
T cells, is a salient feature of the TME in non-responders. Furthermore, cell community analysis extracted 8 types of cell-cell interaction networks termed cellular communities (CCs). We observed that in non-responders, macrophage-enriched CC (MCC) and lymphocyte-enriched CC (LCC) strongly communicate with tumor CC, whereas in responders, such communications were undermined by the engagement between MCC and LCC.
These results demonstrate the feasibility of a novel application of multiplexed image analysis that is broadly applicable to quantitative analysis of pathology specimens in immuno-oncology and provides further evidence that CD163
Arg1
macrophages may be a therapeutic target in HCC. The results also provide critical information for the development of mechanistic quantitative systems pharmacology models aimed at predicting outcomes of clinical trials.
Theaceae, comprising 300 + species, holds significance in biodiversity, economics, and culture, notably including the globally consumed tea plant. Stewartia gemmata, a species of the earliest ...diverging tribe Stewartieae, is critical to offer insights into Theaceae's origin and evolutionary history.
We sequenced the complete organelle genomes of Stewartia gemmata using short/long reads sequencing technologies. The chloroplast genome (158,406 bp) exhibited a quadripartite structure including the large single-copy region (LSC), a small single-copy region (SSC), and a pair of inverted repeat regions (IRs); 114 genes encoded 80 proteins, 30 tRNAs, and four rRNAs. The mitochondrial genome (681,203 bp) exhibited alternative conformations alongside a monocyclic structure: 61 genes encoding 38 proteins, 20 tRNAs, three rRNAs, and RNA editing-impacting genes, including ATP6, RPL16, COX2, NAD4L, NAD5, NAD7, and RPS1. Comparative analyses revealed frequent recombination events and apparent rRNA gene gains and losses in the mitochondrial genome of Theaceae. In organelle genomes, the protein-coding genes exhibited a strong A/U bias at codon endings; ENC-GC3 analysis implies selection-driven codon bias. Transposable elements might facilitate interorganelle sequence transfer. Phylogenetic analysis confirmed Stewartieae's early divergence within Theaceae, shedding light on organelle genome characteristics and evolution in Theaceae.
We studied the detailed characterization of organelle genomes, including genome structure, composition, and repeated sequences, along with the identification of lateral gene transfer (LGT) events and complexities. The discovery of a large number of repetitive sequences and simple sequence repeats (SSRs) has led to new insights into molecular phylogenetic markers. Decoding the Stewartia gemmata organellar genome provides valuable genomic resources for further studies in tea plant phylogenomics and evolutionary biology.
The sandwich foam materials of wind turbine blades are mainly polyvinyl chloride (PVC) and styrene–acrylonitrile (SAN) foams due to their good mechanical properties. However, PVC foam is unrecyclable ...and not resistant to high‐temperature conditions, while SAN foam is more expensive than PVC foam. Polyethylene terephthalate (PET) has irreplaceable advantages than both PVC and SAN foams because of its better mechanical performance, fantastic heat‐resistant, low cost, and environmental friendliness (100% recyclability). In this article, the mechanical properties, thermal stability, resin uptake, and cellular morphology of PET T92, PVC H60, and SAN T400 foams were discussed. The results showed that the mechanical properties of T92 were equivalent to the existing H60 and T400, and even exceed their properties. It was found that the thermal stability of T92 was better than H60 and T400 under the same high temperature. Moreover, the pore of T92 was more uniform and regular than H60 and T400. Furthermore, the overall cost of T92 was lower than H60 and T400. The findings suggest that PET foam with a density of 100 kg/m3 can completely replace PVC 60 kg/m3 and SAN 71 kg/m3 foams from the perspective of mechanical performance, cost, thermal stability, and environmental protection.
The purpose of this paper is to investigate the problem of
controller design for synchronization of the chaotic drive and response systems accompanied with bounded time delays limited by delay rates, ...uncertain parameters and admissible destabilization. An adequate condition is obtained employing the linear matrix inequality and a neoteric Lyapunov-Krasovskii functional to guarantee the global exponential synchronization of the studied chaotic systems. A control law is applied which would be added to the studied systems such that we can ensure the synchronization of the objective systems. The approach is proposed to solve the problem of the asymptotic
synchronization of the studied systems. Numerical examples are illustrated to prove the feasibility and effectiveness of the current approach in this paper.
Quantitative systems pharmacology (QSP) models and spatial agent-based models (ABM) are powerful and efficient approaches for the analysis of biological systems and for clinical applications. ...Although QSP models are becoming essential in discovering predictive biomarkers and developing combination therapies through in silico virtual trials, they are inadequate to capture the spatial heterogeneity and randomness that characterize complex biological systems, and specifically the tumor microenvironment. Here, we extend our recently developed spatial QSP (spQSP) model to analyze tumor growth dynamics and its response to immunotherapy at different spatio-temporal scales. In the model, the tumor spatial dynamics is governed by the ABM, coupled to the QSP model, which includes the following compartments: central (blood system), tumor, tumor-draining lymph node, and peripheral (the rest of the organs and tissues). A dynamic recruitment of T cells and myeloid-derived suppressor cells (MDSC) from the QSP central compartment has been implemented as a function of the spatial distribution of cancer cells. The proposed QSP-ABM coupling methodology enables the spQSP model to perform as a coarse-grained model at the whole-tumor scale and as an agent-based model at the regions of interest (ROIs) scale. Thus, we exploit the spQSP model potential to characterize tumor growth, identify T cell hotspots, and perform qualitative and quantitative descriptions of cell density profiles at the invasive front of the tumor. Additionally, we analyze the effects of immunotherapy at both whole-tumor and ROI scales under different tumor growth and immune response conditions. A digital pathology computational analysis of triple-negative breast cancer specimens is used as a guide for modeling the immuno-architecture of the invasive front.
Spatial heterogeneity is a hallmark of cancer. Tumor heterogeneity can vary with time and location. The tumor microenvironment (TME) encompasses various cell types and their interactions that impart ...response to therapies. Therefore, a quantitative evaluation of tumor heterogeneity is crucial for the development of effective treatments. Different approaches, such as multiregional sequencing, spatial transcriptomics, analysis of autopsy samples, and longitudinal analysis of biopsy samples, can be used to analyze the intratumoral heterogeneity (ITH) and temporal evolution and to reveal the mechanisms of therapeutic response. However, because of the limitations of these data and the uncertainty associated with the time points of sample collection, having a complete understanding of intratumoral heterogeneity role is challenging. Here, we used a hybrid model that integrates a whole-patient compartmental quantitative-systems-pharmacology (QSP) model with a spatial agent-based model (ABM) describing the TME; we applied four spatial metrics to quantify model-simulated intratumoral heterogeneity and classified the TME immunoarchitecture for representative cases of effective and ineffective anti-PD-1 therapy. The four metrics, adopted from computational digital pathology, included mixing score, average neighbor frequency, Shannon's entropy and area under the curve (AUC) of the G-cross function. A fifth non-spatial metric was used to supplement the analysis, which was the ratio of the number of cancer cells to immune cells. These metrics were utilized to classify the TME as "cold", "compartmentalized" and "mixed", which were related to treatment efficacy. The trends in these metrics for effective and ineffective treatments are in qualitative agreement with the clinical literature, indicating that compartmentalized immunoarchitecture is likely to result in more efficacious treatment outcomes.
Overwhelming evidence has shown the significant role of the tumor microenvironment (TME) in governing the triple-negative breast cancer (TNBC) progression. Digital pathology can provide key ...information about the spatial heterogeneity within the TME using image analysis and spatial statistics. These analyses have been applied to CD8+ T cells, but quantitative analyses of other important markers and their correlations are limited. In this study, a digital pathology computational workflow is formulated for characterizing the spatial distributions of five immune markers (CD3, CD4, CD8, CD20, and FoxP3) and then the functionality is tested on whole slide images from patients with TNBC. The workflow is initiated by digital image processing to extract and colocalize immune marker-labeled cells and then convert this information to point patterns. Afterward invasive front (IF), central tumor (CT), and normal tissue (N) are characterized. For each region, we examine the intra-tumoral heterogeneity. The workflow is then repeated for all specimens to capture inter-tumoral heterogeneity. In this study, both intra- and inter-tumoral heterogeneities are observed for all five markers across all specimens. Among all regions, IF tends to have higher densities of immune cells and overall larger variations in spatial model fitting parameters and higher density in cell clusters and hotspots compared to CT and N. Results suggest a distinct role of IF in the tumor immuno-architecture. Though the sample size is limited in the study, the computational workflow could be readily reproduced and scaled due to its automatic nature. Importantly, the value of the workflow also lies in its potential to be linked to treatment outcomes and identification of predictive biomarkers for responders/non-responders, and its application to parameterization and validation of computational immuno-oncology models.
This paper focuses on consensus of the nonholonomic wheeled mobile robotic systems whose geometric center and centroid do not coincide. A consensus control algorithm for mobile robots based on the ...nonstandard chain systems is proposed. Firstly, coordinate transformation is used to transform the nonholonomic robotic systems into the nonstandard chain model. Then, a distributed cooperative control algorithm is designed, and the Lyapunov stability theorem and LaSalle invariance principle are used to prove that each state of the mobile robot is consensus. Finally, the effectiveness of the algorithm is proved through numerical simulation.
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