Selective filling of n-hexane in a tight nanopore

Partial funding for Open Access provided by the UMD Libraries' Open Access Publishing Fund.Molecular sieving may occur when two molecules compete for a nanopore. In nearly all known examples, the nanopore is larger than the molecule that selectively enters the pore. Here, we experimentally demonstrate the ability of single-wall carbon nanotubes with a van der Waals pore size of 0.42 nm to separate n-hexane from cyclohexane—despite the fact that both molecules have kinetic diameters larger than the rigid nanopore. This unexpected finding challenges our current understanding of nanopore selectivity and how molecules may enter a tight channel. Ab initio molecular dynamics simulations reveal that n-hexane molecules stretch by nearly 11.2% inside the nanotube pore. Although at a relatively low probability (28.5% overall), the stretched state of n-hexane does exist in the bulk solution, allowing the molecule to enter the tight pore even at room temperature. These insights open up opportunities to engineer nanopore selectivity based on the molecular degrees of freedom.https://doi.org/10.1038/s41467-020-20587-

Novel Yersinia enterocolitica Prophages and a Comparative Analysis of Genomic Diversity

Yersinia enterocolitica is a major agent of foodborne diseases worldwide. Prophage plays an important role in the genetic evolution of the bacterial genome. Little is known about the genetic information about prophages in the genome of Y. enterocolitica, and no pathogenic Y. enterocolitica prophages have been described. In this study, we induced and described the genomes of six prophages from pathogenic Y. enterocolitica for the first time. Phylogenetic analysis based on whole genome sequencing revealed that these novel Yersinia phages are genetically distinct from the previously reported phages, showing considerable genetic diversity. Interestingly, the prophages induced from O:3 and O:9 Y. enterocolitica showed different genomic sequences and morphology but highly conserved among the same serotype strains, which classified into two diverse clusters. The three long-tailed Myoviridae prophages induced from serotype O:3 Y. enterocolitica were highly conserved, shared ≥99.99% identity and forming genotypic cluster A; the three Podoviridae prophages induced from the serotype O:9 strains formed cluster B, also shared more than 99.90% identity with one another. Cluster A was most closely related to O:5 non-pathogenic Y. enterocolitica prophage PY54 (61.72% identity). The genetic polymorphism of these two kinds of prophages and highly conserved among the same serotype strains, suggested a possible shared evolutionary past for these phages: originated from distinct ancestors, and entered pathogenic Y. enterocolitica as extrachromosomal genetic components during evolution when facing selective pressure. These results are critically important for further understanding of phage roles in host physiology and the pathology of disease

RAGE Mediates Accelerated Diabetic Vein Graft Atherosclerosis Induced by Combined Mechanical Stress and AGEs via Synergistic ERK Activation

Aims/Hypothesis: Diabetes with hypertension rapidly accelerates vascular disease, but the underlying mechanism remains unclear. We evaluated the hypothesis that the receptor of advanced glycation end products (RAGE) might mediate combined signals initiated by diabetes-related AGEs and hypertension-induced mechanical stress as a common molecular sensor. Methods: In vivo surgical vein grafts created by grafting vena cava segments from C57BL/6J mice into the common carotid arteries of streptozotocin (STZ)-treated and untreated isogenic mice for 4 and 8 weeks were analyzed using morphometric and immunohistochemical techniques. In vitro quiescent mouse vascular smooth muscle cells (VSMCs) with either knockdown or overexpression of RAGE were subjected to cyclic stretching with or without AGEs. Extracellular signalregulated kinase (ERK) phosphorylation and Ki-67 expression were investigated. Results: Significant increases in neointimal formation, AGE deposition, Ki-67 expression, and RAGE were observed in the vein grafts of STZ-induced diabetic mice. The highest levels of ERK phosphorylation and Ki-67 expression in VSMCs were induced by simultaneous stretch stress and AGE exposure. The synergistic activation of ERKs and Ki-67 in VSMCs was significantly inhibited by siRNA-RAGE treatment and enhanced by over-expression of RAGE. Conclusion: RAGE may mediate synergistically increased ERK activation and VSMC proliferation induced by mechanica

Non-coding RNA Contribution to Thoracic and Abdominal Aortic Aneurysm Disease Development and Progression

Multiple research groups have started to uncover the complex genetic and epigenetic machinery necessary to maintain cardiovascular homeostasis. In particular, the key contribution of non-coding RNAs (ncRNAs) in regulating gene expression has recently received great attention. Aneurysms in varying locations of the aorta are defined as permanent dilations, predisposing to the fatal consequence of rupture. The characteristic pathology of an aneurysm is characterized by progressive vessel wall dilation, promoted by dying vascular smooth muscle cells and limited proliferation, as well as impaired synthesis and degradation of extracellular matrix components, which at least partially is the result of transmural inflammation and its disruptive effect on vessel wall homeostasis. Currently no conservative pharmacological approach exists that could slow down aneurysm progression and protect from the risk of acute rupture. In the recent past, several non-coding RNAs (mainly microRNAs) have been discovered as being involved in aneurysm progression throughout varying locations of the aorta. Exploring ncRNAs as key regulators and potential therapeutic targets by using antisense oligonucleotide strategies could open up promising opportunities for patients in the near future. Purpose of this current review is to summarize current findings and novel concepts of perspectivly utilizing ncRNAs for future therapeutic and biomarker applications

Design of Elastomer-CNT Film Photoactuators for Nanolithography

Polymer pen lithography (PPL) is an approach to multiplexing scanning probe lithography, in which an array of probes on a compliant film-coated rigid substrate are used to write patterns on a surface. Recently, it was shown that these nominally passive pen arrays can be rendered photo-active by making them out of a polydimethylsiloxane (PDMS)–carbon nanotube (CNT) composite. While such photoactuated pens in principle represent a rapid, maskless, and versatile nanomanufacturing strategy, a key challenge that remains is learning how to effectively control the writing of each pen, individually. In this research, we studied the design of PDMS–CNT thin-film photoactuators and experimentally explored the role of illumination radius, film thickness, and CNT concentration. Additionally, we have proposed a model that predicts actuation efficiency, actuation time, and the crosstalk between pens. Based upon these results, we have generated a map of working efficiency to elucidate the ideal choice for specific actuation requirements. This work lays the foundation for studying further photoactuatable composite films as actuators in applications beyond lithography including soft robotics and adaptive optics

Cycloaddition of cyclobutenone and azomethine imine enabled by chiral isothiourea organic catalysts

The addition of an organic catalyst to the ketone moiety of a γ-mono-chloride substituted cyclobutenone destroys its stable, conjugated and nearly planar structure. The C–C bond in the resulting less stable anionic oxy-substituted non-planar intermediate is then activated. The breaking of one C–C single bond leads to a catalyst-bound intermediate that undergoes α-carbon selective reactions with azomethine imines to afford nitrogen-containing heterocyclic compounds with excellent diastereo- and enantio-selectivities. Our organocatalytic approach provides a new reaction pattern for C–C bond activation of cyclobutenones that is unavailable with transition metal catalysis. In addition, the present study with isothioureas as the organocatalysts expands the potential in using organocatalysts for C–C bond breaking and selective reactions.Published versio

Measurement of Pharmacokinetics and Tissue Distribution of Four Compounds from Nauclea officinalis in Rat Plasma and Tissues through HPLC-MS/MS

A rapid, sensitive, selective, and accurate HPLC–MS/MS method was developed and validated for the simultaneous determination of chlorogenic acid, naucleactonin C, khaephuoside A 3,4-dimethoxyphenyl-1-O-β-apiofuroseyl(1 ⟶ 2)-β-D-glucopyranoside in rat plasma and tissues after oral administration of Nauclea officinalis extracts. Chloramphenicol was used as an internal standard (IS). The plasma and tissue samples were extracted by protein precipitation with methanol-ethyl acetate (1 : 1, v/v) including 0.1% (v/v) formic acid. The chromatographic separation was achieved by using an C18 column with gradient elution using mobile phase, which consisted of 0.1% formic acid water (A) and acetonitrile (B) and the flow rate of 0.8 mL/min. Mass spectrometric detection was performed in multiple reaction monitoring (MRM) mode utilizing electrospray ionization (ESI) in negative mode. The developed method exhibited good linearity (determination coefficients, R2 ≥ 0.9849), and the lower limits of quantification were 2, 5, 5, and 25 ng/mL for chlorogenic acid, naucleactonin C, khaephuoside A, and 3,4-dimethoxyphenyl-1-O-β-apiofuroseyl(1 ⟶ 2)-β-D-glucopyranoside. The intraday and interday precisions (relative standard deviation, RSD) were less than 12.65%, while the accuracy was ranged from 86.31 to 114.17%. The recovery rate were 51.85–97.06%, 75.99–106.68%, 77.46–105.35%, and 68.36–103.75% for chlorogenic acid, naucleactonin C, khaephuoside A, and 3,4-dimethoxyphenyl-1-O-β-apiofuroseyl(1 ⟶ 2)-β-D-glucopyranoside the matrix effects were 50.17–116.62%, 86.75–115.99%, 45.79–87.44%, and 51.60–92.34% for chlorogenic acid, naucleactonin C, khaephuoside A, and 3,4-dimethoxyphenyl-1-O-β-apiofuroseyl(1 ⟶ 2)-β-D-glucopyranoside in different matrix. The developed method was successfully applied to a pharmacokinetic study and tissue distribution of four compounds in rats after oral administration of Nauclea officinalis extracts