A sol–gel synthesis to prepare size and shape-controlled mesoporous nanostructures of binary (II–VI) metal oxides

A base-catalyzed sol–gel approach combined with a solvent-driven self-assembly process at low temperature is augmented to make manganese oxide (Mn₃O₄), copper oxide (CuO), and magnesium hydroxide (Mg(OH)₂) nanostructures with size- and shape-controlled morphologies. Nanostructures of Mn₃O₄ with either hexagonal, irregular particle, or ribbon shape morphologies with an average diameter ranged from 100 to 200 nm have been prepared in four different solvent types. In all morphologies of Mn₃O₄, the experimental XRD patterns have indexed the nanocrystal unit cell structure to triclinic. The hexagonal nanoparticles of Mn₃O₄ exhibit high mesoporocity with a BET surface area of 91.68 m² g⁻¹ and BJH desorption average pore diameter of ∼28 nm. In the preparation of CuO nanostructures, highly nanoporous thin sheets have been produced in water and water/toluene solvent systems. The simulated XRD pattern matches the experimental XRD patterns of CuO nanostructures and indexes the nanocrystal unit cell structure to monoclinic. With the smallest desorption total pore volume of 0.09 cm³ g⁻¹, CuO nanosheets have yielded the lowest BET surface area of 18.31 m² g⁻¹ and a BHJ desorption average pore diameter of ∼16 nm. The sol of magnesium hydroxide nanocrystals produces highly nanoporous hexagonal nanoplates in water and water/toluene solvent systems. The wide angle powder XRD patterns show well-defined Bragg''s peaks, indexing to a hexagonal unit cell structure. The hexagonal plates show a significantly high BET surface area (72.31 m² g⁻¹), which is slightly lower than the surface area of Mn₃O₄ hexagonal nanoparticles. The non-template driven sol–gel synthesis process demonstrated herein provides a facile method to prepare highly mesoporous and nanoporous nanostructures of binary (II–IV) metal oxides and their hydroxide derivatives, enabling potential nanostructure platforms with high activities and selectivities for catalysis applications.

A base-catalyzed sol–gel approach combined with a solvent-driven self-assembly process at low temperature is augmented to make highly mesoporous metal oxide nanostructures of manganese and copper, and hydroxide nanostructures of magnesium.     

Novel biodegradable low-κ dielectric nanomaterials from natural polyphenols

Biodegradable natural polymers and macromolecules for transient electronics have great potential to reduce the environmental footprint and provide opportunities to create emerging and environmentally sustainable technologies. Creating complex electronic devices from biodegradable materials requires exploring their chemical design pathways to use them as substrates, dielectric insulators, conductors, and semiconductors. While most research exploration has been conducted using natural polymers as substrates for electronic devices, a very few natural polymers have been explored as dielectric insulators, but they possess high dielectric constants. Herein, for the first time, we have demonstrated a natural polyphenol-based nanomaterial, derived from tannic acid as a low-κ dielectric material by introducing a highly nanoporous framework with a silsesquioxane core structure. Utilizing natural tannic acid, porous “raspberry-like” nanoparticles (TA-NPs) are prepared by a sol–gel polymerization method, starting from reactive silane unit-functionalized tannic acid. Particle composition, thermal stability, porosity distribution, and morphology are analyzed, confirming the mesoporous nature of the nanoparticles with an average pore diameter ranging from 19 to 23 nm, pore volume of 0.032 cm³ g⁻¹ and thermal stability up to 350 °C. The dielectric properties of the TA-NPs, silane functionalized tannic acid precursor, and tannic acid are evaluated and compared by fabricating thin film capacitors under ambient conditions. The dielectric constants (κ) are found to be 2.98, 2.84, and 2.69 (±0.02) for tannic acid, tannic acid-silane, and TA-NPs, respectively. The unique chemical design approach developed in this work provides us with a path to create low-κ biodegradable nanomaterials from natural polyphenols by weakening their polarizability and introducing high mesoporosity into the structure.

The first study on biodegradable low-κ dielectric nanomaterials with a silsesquioxane framework is demonstrated utilizing a natural polyphenol, tannic acid.     

In vivo comparison of tantalum,tungsten, and bismuth enteric contrast agents to complement intravenous iodine for double‐contrast dual‐energy CT of the bowel

To assess the ability of dual‐energy CT (DECT) to separate intravenous contrast of bowel wall from intraluminal contrast, we scanned 16 rabbits on a clinical DECT scanner: n = 3 using only iodinated intravenous contrast, and n = 13 double‐contrast enhanced scans using iodinated intravenous contrast and experimental enteric non‐iodinated contrast agents in the bowel lumen (five bismuth, four tungsten, and four tantalum based). Representative image pairs from conventional CT images and DECT iodine density maps of small bowel (116 pairs from 232 images) were viewed by four abdominal imaging attending radiologists to independently score each comparison pair on a visual analog scale (?100 to +100%) for (1) preference in small bowel wall visualization and (2) preference in completeness of intraluminal enteric contrast subtraction. Median small bowel wall visualization was scored 39 and 42 percentage points (95% CI 30–44% and 36–45%, both p < 0.001) higher for double‐contrast DECT than for conventional CT with enteric tungsten and tantalum contrast, respectively. Median small bowel wall visualization for double‐contrast DECT was scored 29 and 35 percentage points (95% CI 20–35% and 33–39%, both p < 0.001) higher with enteric tungsten and tantalum, respectively, than with bismuth contrast. Median completeness of intraluminal enteric contrast subtraction in double‐contrast DECT iodine density maps was scored 28 and 29 percentage points (95% CI 15–31% and 28–33%, both p < 0.001) higher with enteric tungsten and tantalum, respectively, than with bismuth contrast. Results suggest that in vivo double‐contrast DECT with iodinated intravenous and either tantalum‐ or tungsten‐based enteric contrast provides better visualization of small bowel than conventional CT. Copyright © 2016 John Wiley & Sons, Ltd.     

Genotyping of Enterococcus faecalis and Enterococcus faecium isolates by use of a set of eight single nucleotide polymorphisms

A single nucleotide polymorphism (SNP) genotyping method for Enterococcus faecalis and Enterococcus faecium was developed using the "Minimum SNPs" program. SNP sets were interrogated using allele-specific real-time PCR. SNP typing subdivided clonal complexes 2 and 9 of E. faecalis and 17 of E. faecium, members of which cause the majority of nosocomial infections globally.     

Semiparametric modeling and analysis of longitudinal method comparison data

Studies comparing two or more methods of measuring a continuous variable are routinely conducted in biomedical disciplines with the primary goal of measuring agreement between the methods. Often, the data are collected by following a cohort of subjects over a period of time. This gives rise to longitudinal method comparison data where there is one observation trajectory for each method on every subject. It is not required that observations from all methods be available at each observation time. The multiple trajectories on the same subjects are dependent. We propose modeling the trajectories nonparametrically through penalized regression splines within the framework of mixed‐effects models. The model also uses random effects of subjects and their interactions to capture dependence in observations from the same subjects. It additionally allows the within‐subject errors of each method to be correlated. It is fit using the method of maximum likelihood. Agreement between the methods is evaluated by performing inference on measures of agreement, such as concordance correlation coefficient and total deviation index, which are functions of parameters of the assumed model. Simulations indicate that the proposed methodology performs reasonably well for 30 or more subjects. Its application is illustrated by analyzing a dataset of percentage body fat measurements. Copyright © 2017 John Wiley & Sons, Ltd.     

Structural basis for Clostridium perfringens enterotoxin targeting of claudins at tight junctions in mammalian gut

The bacterium Clostridium perfringens causes severe, sometimes lethal gastrointestinal disorders in humans, including enteritis and enterotoxemia. Type F strains produce an enterotoxin (CpE) that causes the third most common foodborne illness in the United States. CpE induces gut breakdown by disrupting barriers at cell–cell contacts called tight junctions (TJs), which are formed and maintained by claudins. Targeted binding of CpE to specific claudins, encoded by its C-terminal domain (cCpE), loosens TJ barriers to trigger molecular leaks between cells. Cytotoxicity results from claudin-bound CpE complexes forming pores in cell membranes. In mammalian tissues, ∼24 claudins govern TJ barriers—but the basis for CpE’s selective targeting of claudins in the gut was undetermined. We report the structure of human claudin-4 in complex with cCpE, which reveals that enterotoxin targets a motif conserved in receptive claudins and how the motif imparts high-affinity CpE binding to these but not other subtypes. The structural basis of CpE targeting is supported by binding affinities, kinetics, and half-lives of claudin–enterotoxin complexes and by the cytotoxic effects of CpE on claudin-expressing cells. By correlating the binding residence times of claudin–CpE complexes we determined to claudin expression patterns in the gut, we uncover that the primary CpE receptors differ in mice and humans due to sequence changes in the target motif. These findings provide the molecular and structural element CpE employs for subtype-specific targeting of claudins during pathogenicity of C. perfringens in the gut and a framework for new strategies to treat CpE-based illnesses in domesticated mammals and humans.

Type F isolates of the pathogenic gram-positive bacterium Clostridium perfringens secrete an enterotoxin (CpE) that afflicts humans and other mammals with very common foodborne and antibiotic-associated forms of gastrointestinal disease, and in some cases severe or fatal enterotoxemia (1, 2). In C. perfringens, sporulation triggers expression and release of CpE into the gastrointestinal tract of its host, where it binds to its cell-surface receptor and induces breakdown of the gastrointestinal barrier and cytotoxicity (1). CpE is 35 kDa in size, has structural homology to β-barrel pore-forming toxins (3), and recognizes and binds its receptors via its C-terminal domain (cCpE) (4, 5). The process of gastrointestinal breakdown in humans initiates with CpE binding to claudins—a 27-member family of plasma membrane proteins that assemble to fortify tight junctions (TJs) in epithelia (Fig. 1A)—and culminates with claudin-bound CpE oligomers that dissociate TJs and form transcellular ion pores that ultimately induce cell death (6).Open in a separate windowFig. 1.Structure of TJs and hCLDN-4. (A) Model epithelial cell–cell contact at a TJ. Claudins are shown in cartoon representation (teal) with accessory proteins called tight junction-associated Marvel proteins (TAMPs). (B) Overall structure of hCLDN-4 (teal, cartoon). Membrane borders (gray, rectangles) and membrane insertion orientation are based on calculations from the PPM server (33).Human claudins range in size from 23 to 34 kDa and are classified by a conserved WGLWCC motif. The 13 “classic” human claudins have additional homology outside of this motif and share 30 to 71% sequence identity (SI Appendix, Fig. S1) (7). Claudins have conserved structural topologies that consist of four ⍺-helical transmembrane (TM) segments and two extracellular segments (ECSs) that form from a five-stranded antiparallel β-sheet (SI Appendix, Fig. S2A) (8–12). ECS1 contains β-strands 1 to 4 and links TM1 to TM2, while ECS2 contains β5 and links TM3 to TM4. Claudin TM and ECS domains interact laterally in cis (SI Appendix, Fig. S2B) and perpendicularly in trans, forming permselective barriers to ions while simultaneously adhering adjacent cells. Both interaction types serve as the foundation for TJ ultrastructure and function (13, 14).CpE may disrupt gut integrity through toxin-induced dissociation of claudin cis and trans interactions, leading to breakdown of TJ barrier function, in addition to killing epithelial cells via a claudin-bound ion pore (9, 10, 12). The gastrointestinal-specific expression of a claudin is not requisite for CpE binding, however, as subtypes with no to low gut abundance bind CpE due to claudin sequence and structural conservation (9, 12, 15). Yet, sufficient sequence and structure divergence exists to impart only select subtypes the ability to bind CpE (16, 17). The recalcitrant nature of claudins to in vitro and in vivo biochemical and biophysical study has yielded contradictory findings concerning which subtypes are physiological CpE receptors, and a lack of quantitative data on claudin–CpE interactions obscures the subtle structural differences that must arise in receptor and nonreceptor claudins (16).Claudin-3 and -4 were the first CpE receptors identified in humans and mice (4, 5). In the gut of these mammals, expression patterns and levels of claudin-3 and -4 vary (15, 18). In humans, CpE incidence in the small intestine causes morphological tissue damage and a reduction in TJ barrier integrity in vitro, while incidence in the large intestine exhibits no effect (19). Human claudin-3 and -4 overabundance in the large but not the small intestine does not coincide with CpE’s requirements for pathogenesis, making their receptor capacities unclear. In mice, claudin-3 and -4 overexpress in the small intestine, making both candidate CpE receptors. Several other claudins overexpress in subdivisions of human and mouse gut (SI Appendix, Fig. S3), rendering it increasingly challenging to categorize individual subtypes as receptors or nonreceptors for CpE using our current understanding.The structure of human claudin-4 (hCLDN-4) in complex with cCpE allows us to define the features CpE employs for claudin subtype-specific targeting and its action on claudins in cells. Altered in vivo expression patterns of human and mouse claudins, coupled with a lack of biophysical binding data, led us to characterize and quantify CpE’s ability to recognize, bind, and destroy claudin-expressing cells to resolve the structural and functional consequences of CpE targeting. Using these findings, we identify divergence in claudin–CpE binding interactions that explains subtype-specific targeting by CpE and how this process influences cytotoxicity. Our discoveries advance categorization of claudin receptors and nonreceptors for CpE in mammalian gut, and elucidate the molecular mechanism by which CpE prompts targeted dissociation of claudins and the breakdown of TJ barriers.