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Journal of the American Chemical Society Aug 2023Proteins play important roles in the therapeutic, medical diagnostic, and chemical catalysis industries. However, their potential is often limited by their fragile and...
Proteins play important roles in the therapeutic, medical diagnostic, and chemical catalysis industries. However, their potential is often limited by their fragile and dynamic nature outside cellular environments. The encapsulation of proteins in solid materials has been widely pursued as a route to enhance their stability and ease of handling. Nevertheless, the experimental investigation of protein interactions with rationally designed synthetic hosts still represents an area in need of improvement. In this work, we leveraged the tunability and crystallinity of metal-organic frameworks (MOFs) and developed a series of crystallographically defined protein hosts with varying chemical properties. Through systematic studies, we identified the dominating mechanisms for protein encapsulation and developed a host material with well-tailored properties to effectively encapsulate the protein ubiquitin. Specifically, in our mesoporous hosts, we found that ubiquitin encapsulation is thermodynamically favored. A more hydrophilic encapsulation environment with favorable electrostatic interactions induces enthalpically favored ubiquitin-MOF interactions, and a higher pH condition reduces the intraparticle diffusion barrier, both leading to a higher protein loading. Our findings provide a fundamental understanding of host-guest interactions between proteins and solid matrices and offer new insights to guide the design of future protein host materials to achieve optimal protein loading. The MOF modification technique used in this work also demonstrates a facile method to develop materials easily customizable for encapsulating proteins with different surface properties.
Topics: Ubiquitin; Catalysis; Diffusion; Metal-Organic Frameworks; Static Electricity
PubMed: 37463331
DOI: 10.1021/jacs.3c01989 -
European Radiology Mar 2024Whether the alternation of the glymphatic system exists in neurodevelopmental disease still remains unclear. In this study, we investigated structural and functional...
OBJECTIVES
Whether the alternation of the glymphatic system exists in neurodevelopmental disease still remains unclear. In this study, we investigated structural and functional changes in the glymphatic system in the treatment-naïve attention-deficit/hyperactivity disorder (ADHD) children by quantitatively measuring the Virchow-Robin spaces (VRS) volume and diffusion tensor image-analysis along the perivascular space (DTI-ALPS).
METHODS
Forty-seven pediatric ADHD patients and 52 age- and gender-matched typically developing (TD) children were recruited in this prospective study. The VRS volume was calculated using a semi-automated approach in axial T2-weighted images. Diffusivities along the x-, y-, and z-axes in the projection, association, and subcortical neural fiber areas were measured. The ALPS index, a ratio that accentuated water diffusion along the perivascular space, was calculated. The Mann-Whitney U test was used to compare the quantitative parameters; Pearson's correlation was used to analyze the correlation with clinical symptoms.
RESULTS
The cerebral VRS volume (mean, 15.514 mL vs. 11.702 mL) and the VRS volume ratio in the ADHD group were larger than those in the TD group (all p < 0.001). The diffusivity along the x-axis in association fiber area and ALPS index were significantly smaller in the ADHD group vs. TD group (mean, 1.40 vs.1.59, p < 0.05 after false discovery rate adjustment). Besides, the ALPS index was related to inattention symptoms of ADHD (r = - 0.323, p < 0.05).
CONCLUSIONS
Our study suggests that the glymphatic system alternation may participate in the pathogenesis of ADHD, which may be a new research direction for exploring the mechanisms of psycho-behavioral developmental disorders. Moreover, the VRS volume and ALPS index could be used as the metrics for diagnosing ADHD.
CLINICAL RELEVANCE STATEMENT
Considering the potential relevance of the glymphatic system for exploring the mechanisms of attention deficit/hyperactivity, the Virchow-Robin spaces volume and the analysis along the perivascular space index could be used as additional metrics for diagnosing the disorder.
KEY POINTS
• Increased Virchow-Robin space volume and decreased analysis along the perivascular space index were found in the treatment-naïve attention-deficit/hyperactivity disorder children. • The results of this study indicate that the glymphatic system alternation may have a valuable role in the pathogenesis of attention-deficit/hyperactivity disorder. • The analysis along the perivascular space index is correlated with inattention symptoms of attention-deficit/hyperactivity disorder children.
Topics: Humans; Child; Attention Deficit Disorder with Hyperactivity; Prospective Studies; Benchmarking; Diffusion; Image Processing, Computer-Assisted
PubMed: 37673963
DOI: 10.1007/s00330-023-10220-2 -
Chemosphere Aug 2023Soil characteristics play an important role in distribution of light non-aqueous phase liquid (LNAPL) spilled from buried pipeline, and enhanced understanding of...
Soil characteristics play an important role in distribution of light non-aqueous phase liquid (LNAPL) spilled from buried pipeline, and enhanced understanding of distribution is significant to the effective design of soil and groundwater remediation strategies. Therefore, distribution of diesel in soils with different porosity and temperature on the temporal evolution of the diesel migration following the saturation profiles of the two-phase flow in soils were investigated in this study. The diffusion ranges, areas and volumes in both the radial as well as in axial directions of leaked diesel in soils with different porosity and temperature increased with time. Soil porosities played an important role in the distributions when soil temperatures had no effect on distributions of diesel in soils. The distribution areas were 0.385 m, 0.294 m, 0.213 m, and 0.170 m at 60 min when the soils porosities were 0.1, 0.2, 0.3, and 0.4, respectively. The distribution volumes were 0.177 m, 0.125 m, 0.082 m, 0.060 m at 60 min when the soils porosities were 0.1, 0.2, 0.3, and 0.4, respectively. But the distribution areas were 0.213 m at 60 min when the soil temperatures were 286.15 K, 296.15 K, 306.15 K and 316.15 K, respectively. The distribution volumes were 0.082 m at 60 min when the soil temperatures were 286.15 K, 296.15 K, 306.15 K and 316.15 K, respectively. The calculation formulas of distribution areas and volumes of diesel in soils with different porosity and temperature for developing prevention and control strategies in the future were fitted. The seepage velocities of diesel changed sharply around the leakage port and decreased from about 4.9 m/s to 0 within a few millimeters in soils with different porosity. Additionally, the diffusion ranges of leaked diesel in soils with different porosity were different, indicating that soil porosity had a significant impact on seepage velocities and pressures. The seepage velocities fields and pressures fields of diesel in soils with different temperature were same at the leakage velocity of 4.9 m/s. And the study could provide some supports for determination of the safety zone and formulation of emergency response plans for LNAPL leakage accidents.
Topics: Porosity; Temperature; Soil; Soil Pollutants; Diffusion
PubMed: 37146773
DOI: 10.1016/j.chemosphere.2023.138744 -
Physica Medica : PM : An International... Mar 2024Radiotherapy outcome modelling often suffers from class imbalance in the modelled endpoints. One of the main options to address this issue is by introducing new...
PURPOSE
Radiotherapy outcome modelling often suffers from class imbalance in the modelled endpoints. One of the main options to address this issue is by introducing new synthetically generated datapoints, using generative models, such as Denoising Diffusion Probabilistic Models (DDPM). In this study, we implemented DDPM to improve performance of a tumor local control model, trained on imbalanced dataset, and compare this approach with other common techniques.
METHODS
A dataset of 535 NSCLC patients treated with SBRT (50 Gy/5 fractions) was used to train a deep learning outcome model for tumor local control prediction. The dataset included complete treatment planning data (planning CT images, 3D planning dose distribution and patient demographics) with sparsely distributed endpoints (6-7 % experiencing local failure). Consequently, we trained a novel conditional 3D DDPM model to generate synthetic treatment planning data. Synthetically generated treatment planning datapoints were used to supplement the real training dataset and the improvement in the model's performance was studied. Obtained results were also compared to other common techniques for class imbalanced training, such as Oversampling, Undersampling, Augmentation, Class Weights, SMOTE and ADASYN.
RESULTS
Synthetic DDPM-generated data were visually trustworthy, with Fréchet inception distance (FID) below 50. Extending the training dataset with the synthetic data improved the model's performance by more than 10%, while other techniques exhibited only about 4% improvement.
CONCLUSIONS
DDPM introduces a novel approach to class-imbalanced outcome modelling problems. The model generates realistic synthetic radiotherapy planning data, with a strong potential to increase performance and robustness of outcome models.
Topics: Humans; Bisacodyl; Carcinoma, Non-Small-Cell Lung; Diffusion; Lung Neoplasms
PubMed: 38325221
DOI: 10.1016/j.ejmp.2024.103307 -
Journal of Visualized Experiments : JoVE Aug 2023We present a protocol that describes the properties and advantages of using a standalone clinostat incubator for growing, treating, and monitoring 3D cell cultures. The...
We present a protocol that describes the properties and advantages of using a standalone clinostat incubator for growing, treating, and monitoring 3D cell cultures. The clinostat mimics an environment where cells can assemble as highly reproducible spheroids with low shear forces and active nutrient diffusion. We demonstrate that both cancer and non-cancer hepatocytes (HepG2/C3A and THLE-3 cell lines) require 3 weeks of growth prior to achieving functionalities comparable to liver cells. This protocol highlights the convenience of utilizing incubators for 3D cells with cameras monitoring the cell growth, as snapshots can be taken to count and measure spheroids upon treatment. We describe the comparison of THLE-3 and HepG2/C3A cell lines, showing how non-cancerous cell lines can be grown as well as immortalized cancer cells. We demonstrate and illustrate how proteomics experiments can be conducted from a few spheroids, which can be collected without perturbing cell signaling, i.e., no trypsinization required. We show that proteomics analysis can be used to monitor the typical liver phenotype of respiratory chain metabolism and the production of proteins involved in metal detoxification and describe a semi-automated system to count and measure the spheroid's area. Altogether, the protocol presents a toolbox that comprises a phenotypic characterization via image capture and a proteomics pipeline to experiment on 3D cell culture models.
Topics: Cell Culture Techniques, Three Dimensional; Cell Cycle; Cell Line; Cell Proliferation; Diffusion
PubMed: 37607073
DOI: 10.3791/65086 -
Proceedings of the National Academy of... Aug 2023
Topics: Humans; SARS-CoV-2; COVID-19; Diffusion; Physics; Evolution, Molecular
PubMed: 37556488
DOI: 10.1073/pnas.2310999120 -
ACS Sensors Sep 2023Diffusion limitations and nonspecific surface absorption are great challenges for developing micro-/nanoscale affinity biosensors. There are very limited approaches that...
Diffusion limitations and nonspecific surface absorption are great challenges for developing micro-/nanoscale affinity biosensors. There are very limited approaches that can solve these issues at the same time. Here, an acoustic streaming approach enabled by a gigahertz (GHz) resonator is presented to promote mass transfer of analytes through the jet mode and biofouling removal through the shear mode, which can be switched by tuning the deviation angle, α, between the resonator and the sensor. Simulations show that the jet mode (α ≤ 0) drives the analytes in the fluid toward the sensing surface, overcomes the diffusion limitation, and enhances the binding; while the shear mode (0 < α < π/4) provides a scouring action to remove the biofouling from the sensor. Experimental studies were performed by integrating this GHz resonator with optoelectronic sensing systems, where a 34-fold enhancement for the initial binding rate was obtained. Featuring high efficiency, controllability, and versatility, we believe that this GHz acoustic streaming approach holds promise for many kinds of biosensing systems as well as lab-on-chip systems.
Topics: Acoustics; Biofouling; Diffusion
PubMed: 37639526
DOI: 10.1021/acssensors.3c00982 -
Photosynthesis Research Nov 2023Leaf photosynthetic capacity (light-saturated net assimilation rate, A) increases from bottom to top of plant canopies as the most prominent acclimation response to the... (Review)
Review
Leaf photosynthetic capacity (light-saturated net assimilation rate, A) increases from bottom to top of plant canopies as the most prominent acclimation response to the conspicuous within-canopy gradients in light availability. Light-dependent variation in A through plant canopies is associated with changes in key leaf structural (leaf dry mass per unit leaf area), chemical (nitrogen (N) content per area and dry mass, N partitioning between components of photosynthetic machinery), and physiological (stomatal and mesophyll conductance) traits, whereas the contribution of different traits to within-canopy A gradients varies across sites, species, and plant functional types. Optimality models maximizing canopy carbon gain for a given total canopy N content predict that A should be proportionally related to canopy light availability. However, comparison of model expectations with experimental data of within-canopy photosynthetic trait variations in representative plant functional types indicates that such proportionality is not observed in real canopies, and A vs. canopy light relationships are curvilinear. The factors responsible for deviations from full optimality include stronger stomatal and mesophyll diffusion limitations at higher light, reflecting greater water limitations and more robust foliage in higher light. In addition, limits on efficient packing of photosynthetic machinery within leaf structural scaffolding, high costs of N redistribution among leaves, and limited plasticity of N partitioning among components of photosynthesis machinery constrain A plasticity. Overall, this review highlights that the variation of A through plant canopies reflects a complex interplay between adjustments of leaf structure and function to multiple environmental drivers, and that A plasticity is limited by inherent constraints on and trade-offs between structural, chemical, and physiological traits. I conclude that models trying to simulate photosynthesis gradients in plant canopies should consider co-variations among environmental drivers, and the limitation of functional trait variation by physical constraints and include the key trade-offs between structural, chemical, and physiological leaf characteristics.
Topics: Acclimatization; Carbon; Diffusion; Nitrogen; Photosynthesis; Plant Leaves; Light
PubMed: 37615905
DOI: 10.1007/s11120-023-01043-9 -
Bio Systems May 2024Most nutrient uptake problems are modeled by the convection-diffusion equation (CDE) abiding by Fick's law. Because nutrients needed by plants exist in the soil solution...
Most nutrient uptake problems are modeled by the convection-diffusion equation (CDE) abiding by Fick's law. Because nutrients needed by plants exist in the soil solution as a form of ions and the soil is a typical fractal structure of heterogeneity, it makes the solute transport appear anomalous diffusion in soil. Taking anomalous diffusion as a transport process, we propose time and space fractional nutrient uptake models based on the classic Nye-Tinker-Barber model. There does not appear apparent sub-diffusion of nitrate in the time fractional model until four months and the time fractional models are appropriate for describing long-term dynamics and slow sorption reaction; the space fractional model can capture super-diffusion in short term and it is suitable for describing nonlocal phenomena and daily variations driven by transpiration and metabolism; the anomalous diffusion more apparently appears near the root surface in the modeling simulation.
Topics: Plant Roots; Diffusion; Models, Biological; Nutrients; Biological Transport; Soil; Nitrates; Computer Simulation
PubMed: 38599512
DOI: 10.1016/j.biosystems.2024.105210 -
Neural Networks : the Official Journal... Aug 2023This paper investigates the stabilization control of fractional-order memristive neural networks with reaction-diffusion terms. With regard to the reaction-diffusion...
This paper investigates the stabilization control of fractional-order memristive neural networks with reaction-diffusion terms. With regard to the reaction-diffusion model, a novel processing method based on Hardy-Poincarè inequality is introduced, as a result, the diffusion terms are estimated associated with the information of the reaction-diffusion coefficients and the regional feature, which may be beneficial to obtain conditions with less conservatism. Then, based on Kakutani's fixed point theorem of set-valued maps, new testable algebraic conclusion for ensuring the existence of the system's equilibrium point is obtained. Subsequently, by means of Lyapunov stability theory, it is concluded that the resulting stabilization error system is global asymptotic/Mittag-Leffler stable with a prescribed controller. Finally, an illustrative example about is provided to show the effectiveness of the established results.
Topics: Neural Networks, Computer; Diffusion
PubMed: 37307670
DOI: 10.1016/j.neunet.2023.05.042