Nuclear pore complexes (NPCs) form gateways that control molecular exchange between the nucleus and the cytoplasm. They impose a diffusion barrier to macromolecules and enable the selective transport of nuclear transport receptors with bound cargo. The underlying mechanisms that establish these permeability properties remain to be fully elucidated but require unstructured nuclear pore proteins rich in Phe-Gly (FG)-repeat domains of different types, such as FxFG and GLFG. While physical modeling and in vitro approaches have provided a framework for explaining how the FG network contributes to the barrier and transport properties of the NPC, it remains unknown whether the number and/or the spatial positioning of different FG-domains along a cylindrical, ∼40 nm diameter transport channel contributes to their collective properties and function. To begin to answer these questions, we have used DNA origami to build a cylinder that mimics the dimensions of the central transport channel and can house a specified number of FG-domains at specific positions with easily tunable design parameters, such as grafting density and topology. We find the overall morphology of the FG-domain assemblies to be dependent on their chemical composition, determined by the type and density of FG-repeat, and on their architectural confinement provided by the DNA cylinder, largely consistent with here presented molecular dynamics simulations based on a coarse-grained polymer model. In addition, high-speed atomic force microscopy reveals local and reversible FG-domain condensation that transiently occludes the lumen of the DNA central channel mimics, suggestive of how the NPC might establish its permeability properties.

BackgroundThe purpose of this study was to analyze the image heterogeneity of clear-cell renal-cell carcinoma (ccRCC) by computer tomography texture analysis and to provide new objective quantitative imaging parameters for the pre-operative prediction of Fuhrman-grade ccRCC.MethodsA retrospective analysis of 131 cases of ccRCCs was performed by manually depicting tumor areas. Then, histogram-based texture parameters were calculated. The texture-feature values between Fuhrman low- (Grade I-II) and high-grade (Grade III-IV) ccRCCs were compared by two independent sample t-tests (False Discovery Rate correction), and receiver operating characteristic curve (ROC) was used to evaluate the efficacy of using texture features to predict Fuhrman high- and low-grade ccRCCs.ResultsThere were no statistical differences for any texture parameters without filtering (p > 0.05). There was a statistically significant difference between the entropy (fine) of the corticomedullary phase and the entropy (fine and coarse) of the nephrographic phase after Laplace of Gaussian filtering. The area under the ROC of the entropy was between 0.74 and 0.83.ConclusionsComputer tomography texture features can predict the Fuhrman grading of ccRCC pre-operatively, with entropy being the most important imaging marker for clinical application.

Lipid and DNA are abundant biomolecules with critical functions in cells. The water-insoluble, amphipathic lipid molecules are best known for their roles in energy storage (e.g. as triglyceride), signaling (e.g. as sphingolipid), and compartmentalization (e.g. by forming membrane-enclosed bodies). The soluble, highly negatively charged DNA, which stores cells' genetic information, has proven to be an excellent material for constructing programmable nanostructures in vitro thanks to its self-assembling capabilities. These two seemingly distant molecules make contact within cell nuclei, often via lipidated proteins, with proposed functions of modulating chromatin structures. Carefully formulated lipid/DNA complexes are promising reagents for gene therapy. The past few years saw an emerging research field of interfacing DNA nanostructures with lipid membranes, with an overarching goal of generating DNA/lipid hybrid materials that possess novel and controllable structure, dynamics, and function. An arsenal of DNA-based tools has been created to coat, mold, deform, and penetrate lipid bilayers, affording us the ability to manipulate membranes with nanoscopic precision. These membrane engineering methods not only enable quantitative biophysical studies, but also open new opportunities in synthetic biology (e.g. artificial cells) and therapeutics (e.g. drug delivery).

DNA nanotechnology is a unique field, where physics, chemistry, biology, mathematics, engineering, and materials science can elegantly converge. Since the original proposal of Nadrian Seeman, significant advances have been achieved in the past four decades. During this glory time, the DNA origami technique developed by Paul Rothemund further pushed the field forward with a vigorous momentum, fostering a plethora of concepts, models, methodologies, and applications that were not thought of before. This review focuses on the recent progress in DNA origami-engineered nanomaterials in the past five years, outlining the exciting achievements as well as the unexplored research avenues. We believe that the spirit and assets that Seeman left for scientists will continue to bring interdisciplinary innovations and useful applications to this field in the next decade.

Background: We aimed to construct and validate a nomogram model based on the combination of radiomic features and satellite sign number for predicting intracerebral hematoma expansion.Methods: A total of 129 patients from two institutions were enrolled in this study. The preprocessed initial CT images were used for radiomic feature extraction. The ANOVA-Kruskal-Wallis test and least absolute shrinkage and selection operator regression were applied to identify candidate radiomic features and construct the Radscore. A nomogram model was developed by integrating the Radscore with a satellite sign number. The discrimination performance of the proposed model was evaluated by receiver operating characteristic (ROC) analysis, and the predictive accuracy was assessed via a calibration curve. Decision curve analysis (DCA) and Kaplan-Meier (KM) survival analysis were performed to evaluate the clinical value of the model.Results: Four optimal features were ultimately selected and contributed to the Radscore construction. A positive correlation was observed between the satellite sign number and Radscore (Pearson's r: 0.451). The nomogram model showed the best performance with high area under the curves in both training cohort (0.881, sensitivity: 0.973; specificity: 0.787) and external validation cohort (0.857, sensitivity: 0.950; specificity: 0.766). The calibration curve, DCA, and KM analysis indicated the high accuracy and clinical usefulness of the nomogram model for hematoma expansion prediction. Conclusion:A nomogram model of integrated radiomic signature and satellite sign number based on noncontrast CT images could serve as a reliable and convenient measurement of hematoma expansion prediction.

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• Heterogeneity is helpful in predicting ICH enlargement. • CTTA could play an important role in predicting early ICH enlargement. • After filtering, fine texture had the best diagnostic performance. • The histogram-based uniformity parameters can independently predict ICH enlargement. • CTTA is more objective, more comprehensive, more independently operable, than previous methods.

APOBEC3 (A3) proteins are a family of host antiviral restriction factors that potently inhibit various retroviral infections, including human immunodeficiency virus (HIV)-1. To overcome this restriction, HIV-1 virion infectivity factor (Vif) recruits the cellular cofactor CBFb to assist in targeting A3 proteins to a host E3 ligase complex for polyubiquitination and subsequent proteasomal degradation. Intervention of the Vif-A3 interactions could be a promising therapeutic strategy to facilitate A3-mediated suppression of HIV-1 in patients. In this structural snapshot, we review the structural features of the recently determined structure of human A3F in complex with HIV-1 Vif and its cofactor CBFb, discuss insights into the molecular principles of Vif-A3 interplay during the arms race between the virus and host, and highlight the therapeutic implications.