Steric stabilization of colloidal UiO-66 nanocrystals with oleylammonium octadecylphosphonate.

We report the synthesis and characterization of octahedral UiO-66 nanocrystals ( = 17-25 nm) terminated with amine, oleate, and octadecylphosphonate ligands. Acetate capped UiO-66 nanocrystals were dispersed in toluene using oleic acid and oleylamine. Ligand exchange with octadecylphosphonic acid produces ammonium octadecylphosphonate terminated nanocrystals with coverages of 2.

Viscoelasticity of globular protein-based biomolecular condensates.

The phase separation of biomolecules into biomolecular condensates has emerged as a ubiquitous cellular process. Understanding how intrinsically disordered protein sequence controls condensate formation and material properties has provided fundamental biological insights and led to the development of functional synthetic condensates. While these studies provide a valuable framework to understand subcellular organization phase separation they have largely ignored the presence of folded domains and their impact on condensate properties.

Microfluidic measurement of intracellular mRNA with a molecular beacon probe towards point-of-care radiation triage.

In large-scale radiation exposure events, the ability to triage potential victims by the received radiation dosage is crucial. This can be evaluated by radiation-induced biological changes. Radiation-responsive mRNA is a class of biomarkers that has been explored for dose-dependency with methods such as RT-qPCR.

MLstructureMining: a machine learning tool for structure identification from X-ray pair distribution functions.

Synchrotron X-ray techniques are essential for studies of the intrinsic relationship between synthesis, structure, and properties of materials. Modern synchrotrons can produce up to 1 petabyte of data per day. Such amounts of data can speed up materials development, but also comes with a staggering growth in workload, as the data generated must be stored and analyzed.

Testing the hypothesis that solvent exchange limits the rates of calcite growth and dissolution.

It is established that the rates of solvent exchange at interfaces correlate with the rates of a number of mineral reactions, including growth, dissolution and ion sorption. To test if solvent exchange is limiting these rates, quasi-elastic neutron scattering (QENS) is used here to benchmark classical molecular dynamics (CMD) simulations of water bound to nanoparticulate calcite. Four distributions of solvent exchanges are found with residence times of 8.

Transition metal nitride catalysts for selective conversion of oxygen-containing molecules.

Earth abundant transition metal nitrides (TMNs) are a promising group of catalysts for a wide range of thermocatalytic, electrocatalytic and photocatalytic reactions, with potential to achieve high activity and selectivity while reducing reliance on the use of Pt-group metals. However, current fundamental understanding of the active sites of these materials and the mechanisms by which selective transformations occur is somewhat lacking. Recent investigations of these materials from our group and others have utilized probe molecules, model surfaces, and techniques to elucidate the origin of their activity, strong metal-support interactions, and unique d-band electronic structures.

Predicting Clinician Fixations on Glaucoma OCT Reports via CNN-Based Saliency Prediction Methods.

To predict physician fixations specifically on ophthalmology optical coherence tomography (OCT) reports from eye tracking data using CNN based saliency prediction methods in order to aid in the education of ophthalmologists and ophthalmologists-in-training. Fifteen ophthalmologists were recruited to each examine 20 randomly selected OCT reports and evaluate the likelihood of glaucoma for each report on a scale of 0-100. Eye movements were collected using a Pupil Labs Core eye-tracker.

Beyond ManifoldEM: geometric relationships between manifold embeddings of a continuum of 3D molecular structures and their 2D projections.

ManifoldEM is an established method of geometric machine learning developed to extract information on conformational motions of molecules from their projections obtained by cryogenic electron microscopy (cryo-EM). In a previous work, in-depth analysis of the properties of manifolds obtained for simulated ground-truth data from molecules exhibiting domain motions has led to improvements of this method, as demonstrated in selected applications of single-particle cryo-EM. In the present work this analysis has been extended to investigate the properties of manifolds constructed by embedding data from synthetic models represented by atomic coordinates in motion, or three-dimensional density maps from biophysical experiments other than single-particle cryo-EM, with extensions to cryo-electron tomography and single-particle imaging with a X-ray free-electron laser.

DeepStruc: towards structure solution from pair distribution function data using deep generative models.

Structure solution of nanostructured materials that have limited long-range order remains a bottleneck in materials development. We present a deep learning algorithm, DeepStruc, that can solve a simple monometallic nanoparticle structure directly from a Pair Distribution Function (PDF) obtained from total scattering data by using a conditional variational autoencoder. We first apply DeepStruc to PDFs from seven different structure types of monometallic nanoparticles, and show that structures can be solved from both simulated and experimental PDFs, including PDFs from nanoparticles that are not present in the training distribution.

Coupling of α-bromoamides and unactivated alkenes to form γ-lactams through EDA and photocatalysis.

γ-Lactams are prevalent in small-molecule pharmaceuticals and provide useful precursors to highly substituted pyrrolidines. Despite numerous methods for the synthesis of this valuable motif, previous redox approaches to γ-lactam synthesis from α-haloamides and olefins require additional electron withdrawing functionality as well as -aryl substitution to promote electrophilicity of the intermediate radical and prevent competitive O-nucleophilicity about the amide. Using α-bromo imides and α-olefins, our strategy enables the synthesis of monosubstituted protected γ-lactams in a formal [3 + 2] fashion.

Protein charge parameters that influence stability and cellular internalization of polyelectrolyte complex micelles.

Proteins are an important class of biologics, but there are several recurring challenges to address when designing protein-based therapeutics. These challenges include: the propensity of proteins to aggregate during formulation, relatively low loading in traditional hydrophobic delivery vehicles, and inefficient cellular uptake. This last criterion is particularly challenging for anionic proteins as they cannot cross the anionic plasma membrane.

Tuning through-space interactions the secondary coordination sphere of an artificial metalloenzyme leads to enhanced Rh(iii)-catalysis.

We report computationally-guided protein engineering of monomeric streptavidin Rh(iii) artificial metalloenzyme to enhance catalysis of the enantioselective coupling of acrylamide hydroxamate esters and styrenes. Increased TON correlates with calculated distances between the Rh(iii) metal and surrounding residues, underscoring an artificial metalloenzyme's propensity for additional control in metal-catalyzed transformations by through-space interactions.

Microbial nanocellulose biotextiles for a circular materials economy.

The synthesis and bottom-up assembly of nanocellulose by microbes offers unique advantages to tune and meet key design criteria-rapid renewability, low toxicity, scalability, performance, and degradability-for multi-functional, circular economy textiles. However, development of green processing methods that meet these criteria remains a major research challenge. Here, we harness microbial biofabrication of nanocellulose and draw inspiration from ancient textile techniques to engineer sustainable biotextiles with a circular life cycle.

Correction: Biofunctional Janus particles promote phagocytosis of tumor cells by macrophages.

[This corrects the article DOI: 10.1039/D0SC01146K.].

Metal binding and interdomain thermodynamics of mammalian metallothionein-3: enthalpically favoured Cu supplants entropically favoured Zn to form Cu clusters under physiological conditions.

Metallothioneins (MTs) are a ubiquitous class of small metal-binding proteins involved in metal homeostasis and detoxification. While known for their high affinity for d metal ions, there is a surprising dearth of thermodynamic data on metals binding to MTs. In this study, Zn and Cu binding to mammalian metallothionein-3 (MT-3) were quantified at pH 7.

A PVA/LiCl/PEO interpenetrating composite electrolyte with a three-dimensional dual-network for all-solid-state flexible aluminum-air batteries.

Aluminum-air batteries are promising electronic power sources because of their low cost and high energy density. However, traditional aluminum-air batteries are greatly restricted from being used in the field of flexible electronics due to the rigid battery structure, and the irreversible corrosion of the anode by the alkaline electrolyte, which greatly reduces the battery life. To address these issues, a three-dimensional dual-network interpenetrating structure PVA/LiCl/PEO composite gel polymer electrolyte (GPE) is proposed.

Heart-Lung Interactions During Mechanical Ventilation: Analysis via a Cardiopulmonary Simulation Model.

Heart-lung interaction mechanisms are generally not well understood. Mechanical ventilation, for example, accentuates such interactions and could compromise cardiac activity. Thereby, assessment of ventilation-induced changes in cardiac function is considered an unmet clinical need.

DsbA is a redox-switchable mechanical chaperone.

DsbA is a ubiquitous bacterial oxidoreductase that associates with substrates during and after translocation, yet its involvement in protein folding and translocation remains an open question. Here we demonstrate a redox-controlled chaperone activity of DsbA, on both cysteine-containing and cysteine-free substrates, using magnetic tweezers-based single molecule force spectroscopy that enables independent measurements of oxidoreductase activity and chaperone behavior. Interestingly we found that this chaperone activity is tuned by the oxidation state of DsbA; oxidized DsbA is a strong promoter of folding, but the effect is weakened by the reduction of the catalytic CXXC motif.

A Versatile and Robust Platform for the Scalable Manufacture of Biomimetic Nanovaccines.

Biomimetic strategies are useful for designing potent vaccines. Decorating a nanoparticulate adjuvant with cell membrane fragments as the antigen-presenting source exemplifies, such as a promising strategy. For translation, a standardizable, consistent, and scalable approach for coating nanoadjuvant with the cell membrane is important.

Biofunctional Janus particles promote phagocytosis of tumor cells by macrophages.

Herein, a versatile strategy for the construction of biofunctional Janus particles (JPs) through the combination of Pickering emulsion and copper-free click chemistry is developed for the study of particle-mediated cell-cell interactions. A variety of biomolecules including bovine serum albumin (BSA), ferritin, transferrin (Tf), and anti-signal regulatory protein alpha antibodies (aSIRPα), , can be incorporated into the Janus platform in a spatially defined manner. JPs consisting of Tf and aSIRPα (Tf-SPA1-aSIRPα JPs) demonstrate a significantly improved binding affinity to either macrophages or tumor cells compared to their uniformly modified counterparts.

Prediction of drug metabolites using neural machine translation.

Metabolic processes in the human body can alter the structure of a drug affecting its efficacy and safety. As a result, the investigation of the metabolic fate of a candidate drug is an essential part of drug design studies. Computational approaches have been developed for the prediction of possible drug metabolites in an effort to assist the traditional and resource-demanding experimental route.

Molecular mechanism of secreted amyloid-β precursor protein in binding and modulating GABAR1a.

A recent phenomenal study discovered that the extension domain of secreted amyloid-β precursor protein (sAPP) can bind to the intrinsically disordered sushi 1 domain of the γ-aminobutyric acid type B receptor subunit 1a (GABAR1a) and modulate its synaptic transmission. The work provided an important structural foundation for the modulation of GABAR1a; however, the detailed molecular interaction mechanism, crucial for future drug design, remains elusive. Here, we further investigated the dynamical interactions between sAPP peptides and the natively unstructured sushi 1 domain using all-atom molecular dynamics simulations, for both the 17-residue sAPP peptide (APP 17-mer) and its minimally active 9 residue segment (APP 9-mer).

Rationally Programming Nanomaterials with DNA for Biomedical Applications.

DNA is not only a carrier of genetic information, but also a versatile structural tool for the engineering and self-assembling of nanostructures. In this regard, the DNA template has dramatically enhanced the scalability, programmability, and functionality of the self-assembled DNA nanostructures. These capabilities provide opportunities for a wide range of biomedical applications in biosensing, bioimaging, drug delivery, and disease therapy.

Dose-Dependent Carbon-Dot-Induced ROS Promote Uveal Melanoma Cell Tumorigenicity via Activation of mTOR Signaling and Glutamine Metabolism.

Uveal melanoma (UM) is the most common intraocular malignant tumor in adults and has a low survival rate following metastasis; it is derived from melanocytes susceptible to reactive oxygen species (ROS). Carbon dot (Cdot) nanoparticles are a promising tool in cancer detection and therapy due to their unique photophysical properties, low cytotoxicity, and efficient ROS productivity. However, the effects of Cdots on tumor metabolism and growth are not well characterized.

Alveolar Tissue Fiber and Surfactant Effects on Lung Mechanics-Model Development and Validation on ARDS and IPF Patients.

Alveolar compliance is a main determinant of lung airflow. The compliance of the alveoli is a function of their tissue fiber elasticity, fiber volume, and surface tension. The compliance varies during respiration because of the nonlinear nature of fiber elasticity and the time-varying surface tension coating the alveoli.