The mechanical properties of cells change with their differentiation,chronological age,and malignant ***,these properties may be useful label-free biomarkers of various functional or clinically relevant cell ***,we de...
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The mechanical properties of cells change with their differentiation,chronological age,and malignant ***,these properties may be useful label-free biomarkers of various functional or clinically relevant cell ***,we demonstrate mechano-node-pore sensing(mechano-NPS),a multi-parametric single-cell-analysis method that utilizes a four-terminal measurement of the current across a microfluidic channel to quantify simultaneously cell diameter,resistance to compressive deformation,transverse deformation under constant strain,and recovery time after *** define a new parameter,the whole-cell deformability index(wCDI),which provides a quantitative mechanical metric of the resistance to compressive deformation that can be used to discriminate among different cell *** wCDI and the transverse deformation under constant strain show malignant MCF-7 and A549 cell lines are mechanically distinct from non-malignant,MCF-10A and BEAS-2B cell lines,and distinguishes between cells treated or untreated with cytoskeleton-perturbing small *** categorize cell recovery time,ΔT_(r),as instantaneous(ΔTr~0 ms),transient(ΔT_(r)≤40 ms),or prolonged(ΔT_(r)>40 ms),and show that the composition of recovery types,which is a consequence of changes in cytoskeletal organization,correlates with cellular *** the wCDI and cell-recovery time,mechano-NPS discriminates between sub-lineages of normal primary human mammary epithelial cells with accuracy comparable to flow cytometry,but without antibody ***-NPS identifies mechanical phenotypes that distinguishes lineage,chronological age,and stage of malignant progression in human epithelial cells.
We present a technique for automatic brain tumor segmentation in magnetic resonance images, combining a modified version of a Genetic Algorithm Clustering method with an AdaBoost Classifier. In a group of 42 FLAIR ima...
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The goal of this study was to find the most robust algorithm for a phase‐sensitive coil combination of 3D single‐cycle and lactate‐edited, multi‐channel H‐1 point‐resolved spectroscopy (PRESS) localized echo pla...
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The goal of this study was to find the most robust algorithm for a phase‐sensitive coil combination of 3D single‐cycle and lactate‐edited, multi‐channel H‐1 point‐resolved spectroscopy (PRESS) localized echo planar spectroscopic imaging (EPSI) data for clinical applications in the brain. Data were acquired over 5-10 minutes at 3T using 8‐ or 32‐channel array coils. Peak referencing with residual water and N‐acetyl‐aspartate, first‐point phasing, generalized least squared (GLS) and whitened singular‐value decomposition (WSVD) combination algorithms were evaluated relative to unsuppressed water with data from a phantom, six volunteers and 55 patients with brain tumors. Comparison metrics were signal‐to‐noise ratio, coefficient of variance and percent signal increase. Where residual water was present, using it as a reference peak for phasing and weighting factors from an imaging calibration scan gave the best overall performance. Greater improvement was seen for large selected volumes (>720 cm3) and for the 32‐channel array (25%) compared with the 8‐channel array (19%). Applying voxel‐by‐voxel phase corrections produced a larger increase in performance for the 32‐ versus 8‐channel coil. We conclude that, for clinically relevant 3D H‐1 PRESS localized EPSI studies, the most robust technique employed individual phase maps generated from high residual water and individual amplitude maps generated from calibration scans.
The autophagy-lysosomal pathway is a cellular degradation mechanism that regulates protein quality by eliminating aggregates and maintaining normal protein function. It has been reported that aging itself reduces lyso...
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The autophagy-lysosomal pathway is a cellular degradation mechanism that regulates protein quality by eliminating aggregates and maintaining normal protein function. It has been reported that aging itself reduces lysosomal proteolytic activity in age-related neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Reduction in lysosomal function may underlie the accumulation of protein aggregates such as amyloid beta (Aβ), tau, and α-synuclein. Some of these protein aggregates may cause additional lysosomal dysfunction and create a vicious cycle leading to a gradual increase in protein aggregation. In this study, liposome-based lysosomal pH-modulating particles (LPPs), containing a liquid solution to adjust lysosomal pH, have been developed to restore lysosomal function. The results demonstrate that acidic LPPs effectively restore lysosomal function by recovering lysosomal pH and facilitating the removal of protein aggregates. These findings demonstrated that acidic LPPs could effectively recover the abnormal lysosomal function via restoration of lysosomal pH and enhance the clearance of protein aggregates. Furthermore, the simultaneous introduction of Cathepsin B (CTSB) proteins and acidic LPP revealed a synergistic effect, promoting lysosomal pH recovery and enhancing aggregates removal. These findings suggest a novel strategy for improving lysosomal clearance activity in proteinopathies.
Background: The applicability and therapeutic efficacy of specific personalized immunotherapy for cancer patients is limited by the genetic diversity of the host or the tumor. Side-effects such as immune-related adver...
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Background: The applicability and therapeutic efficacy of specific personalized immunotherapy for cancer patients is limited by the genetic diversity of the host or the tumor. Side-effects such as immune-related adverse events (IRAEs) derived from the administration of immunotherapy have also been observed. Therefore, regulatory immunotherapy is required for cancer patients and should be developed. Methods: The cationic lipo-PEG-PEI complex (LPPC) can stably and irreplaceably adsorb various proteins on its surface without covalent linkage, and the bound proteins maintain their original functions. In this study, LPPC was developed as an immunoregulatory platform for personalized immunotherapy for tumors to address the barriers related to the heterogenetic characteristics of MHC molecules or tumor associated antigens (TAAs) in the patient population. Here, the immune-suppressive and highly metastatic melanoma, B16F10 cells were used to examine the effects of this platform. Adsorption of anti-CD3 antibodies, HLA-A2/peptide, or dendritic cells’ membrane proteins (MP) could flexibly provide pan-T-cell responses, specific Th1 responses, or specific Th1 and Th2 responses, depending on the host needs. Furthermore, with regulatory antibodies, the immuno-LPPC complex properly mediated immune responses by adsorbing positive or negative antibodies, such as anti-CD28 or anti-CTLA4 antibodies. Results: The results clearly showed that treatment with LPPC/MP/CD28 complexes activated specific Th1 and Th2 responses, including cytokine release, CTL and prevented T-cell apoptosis. Moreover, LPPC/MP/CD28 complexes could eliminate metastatic B16F10 melanoma cells in the lung more efficiently than LPPC/MP. Interestingly, the melanoma resistance of mice treated with LPPC/MP/CD28 complexes would be reversed to susceptible after administration with LPPC/MP/CTLA4 complexes. NGS data revealed that LPPC/MP/CD28 complexes could enhance the gene expression of cytokine and chemokine pathways to st
The human brain is composed of distinct regions that are each associated with particular functions and distinct propensities for the control of neural dynamics. However, the relation between these functions and contro...
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The human brain is composed of distinct regions that are each associated with particular functions and distinct propensities for the control of neural dynamics. However, the relation between these functions and control profiles is poorly understood, as is the variation in this relation across diverse scales of space and time. Here we probe the relation between control and dynamics in brain networks constructed from diffusion tensor imaging data in a large community sample of young adults. Specifically, we probe the control properties of each brain region and investigate their relationship with dynamics across various spatial scales using the Laplacian eigenspectrum. In addition, through analysis of regional modal controllability and partitioning of modes, we determine whether the associated dynamics are fast or slow, as well as whether they are alternating or monotone. We find that brain regions that facilitate the control of energetically easy transitions are associated with activity on short length scales and slow timescales. Conversely, brain regions that facilitate control of difficult transitions are associated with activity on long length scales and fast timescales. Built on linear dynamical models, our results offer parsimonious explanations for the activity propagation and network control profiles supported by regions of differing neuroanatomical structure.
Optical dynamic focusing has emerged as a speed, complexity and efficiency bottleneck across various applications, which include scanning multi-photon microscopy in biology, maskless lithography and micromachining in ...
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Optical dynamic focusing has emerged as a speed, complexity and efficiency bottleneck across various applications, which include scanning multi-photon microscopy in biology, maskless lithography and micromachining in material processing, and wavefront correction. Here, we present a 32-ring 23,852-pixel concentric micromirror array capable of performing dynamic focusing for wavelengths of up to 1040 nm with a response rate of up to 8.75 kHz, 30 V drive and a focusing full-width-half-maximum to range ratio of 4.8%.
Osteoporotic fractures in older adults place a significant burden on healthcare systems due to prolonged healing times and escalating costs. Innovative approaches closely mimicking the human bone microenvironment are ...
Osteoporotic fractures in older adults place a significant burden on healthcare systems due to prolonged healing times and escalating costs. Innovative approaches closely mimicking the human bone microenvironment are paramount for advancing bone tissue regeneration. This study leverages a sacrificial template methodology to develop hierarchical 3D porous gelatin-NaNbO 3 @PDMS scaffolds with gyroid structures mimicking cancellous bone architecture, tailored for enhanced stimuli-responsive biological performance. Modulating porosity levels (∼0%, 18 %, and 63 %) enables macro-to-micro pore transitions, highlighting how porosity and zero-curvature surfaces impact critical properties for bioactive scaffold applications. Under simulated physical activity pressures, lower scaffold porosity enhances structural integrity, mechanical stability, and damping capacity, driven by reduced thickness plastic deformation. Corona discharge poling generates electrically charged stimuli-responsive scaffolds, enhancing electric field intensity through charge trapping. Combined with ultrasound stimulation (50 and 250 mW·cm −2 ), it boosts metabolic activity, gene expression, and mineralization, increasing calcium deposition by up to 1200 % compared to unstimulated controls. Finite element analysis reveals that the 63 % porosity scaffolds generate a sixfold stronger electric field than its 18 % counterpart, enhancing stimuli-responsive cell alignment, with ultrasound stimulation boosting it by ∼10 %. These discoveries in zero-curvature geometries and stimuli-responsive systems redefine bone regeneration strategies by mimicking bone anisotropy through electric field stimulation, offering transformative insights for advanced biomaterials in implants and physiotherapy.
Purpose: To develop a high scanning efficiency, motion corrected imaging strategy for free-breathing pulmonary MRI by combining a motion compensation reconstruction with a UTE acquisition, called iMoCo UTE. Methods: A...
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