Applying reticular synthesis to the design of Cu-based MOFs with mechanically interlocked linkers

The concept of“robust dynamics”describes the incorporation of mechanically interlocked molecules(MIMs)into metal-organic framework(MOF)materials such that large amplitude motions(e.g.,rotation or translation of a macrocycle)can occur inside the free volume pore of the MOF.To aid in the preparation of such materials,reticular synthesis was used herein to design rigid molecular building blocks with predetermined ordered structures starting from the well-known MOF NOTT-101.New linkers were synthesized that have a T-shape,based on a triphenylene tetra-carboxylate strut,and their incorporation into Cu(II)-based MOFs was investigated.The single-crystal structures of three new MOFs,UWCM-12(fof),β-UWCM-13(loz),UWCM-14(lil),with naked T-shaped linkers were determined;β-UWCM-13 is the first reported example of the loz topology.A fourth MOF,UWDM-14(lil)is analogous to UWCM-14(lil)but contains a[2]rotaxane linker.Variable-temperature,²H solid-state NMR was used to probe the dynamics of a 24-membered macrocycle threaded onto the MOF skeleton.     

Design and Characterization of Myristoylated and Non-Myristoylated Peptides Effective against Candida spp. Clinical Isolates

The increasing resistance of fungi to antibiotics is a severe challenge in public health, and newly effective drugs are required. Promising potential medications are lipopeptides, linear antimicrobial peptides (AMPs) conjugated to a lipid tail, usually at the N-terminus. In this paper, we investigated the in vitro and in vivo antifungal activity of three short myristoylated and non-myristoylated peptides derived from a mutant of the AMP Chionodracine. We determined their interaction with anionic and zwitterionic membrane-mimicking vesicles and their structure during this interaction. We then investigated their cytotoxic and hemolytic activity against mammalian cells. Lipidated peptides showed a broad spectrum of activity against a relevant panel of pathogen fungi belonging to Candida spp., including the multidrug-resistant C. auris. The antifungal activity was also observed vs. biofilms of C. albicans, C. tropicalis, and C. auris. Finally, a pilot efficacy study was conducted on the in vivo model consisting of Galleria mellonella larvae. Treatment with the most-promising myristoylated peptide was effective in counteracting the infection from C. auris and C. albicans and the death of the larvae. Therefore, this myristoylated peptide is a potential candidate to develop antifungal agents against human fungal pathogens.     

The Role of Exosomes in Cancer Progression

Early detection, characterization and monitoring of cancer are possible by using extracellular vesicles (EVs) isolated from non-invasively obtained liquid biopsy samples. They play a role in intercellular communication contributing to cell growth, differentiation and survival, thereby affecting the formation of tumor microenvironments and causing metastases. EVs were discovered more than seventy years ago. They have been tested recently as tools of drug delivery to treat cancer. Here we give a brief review on extracellular vesicles, exosomes, microvesicles and apoptotic bodies. Exosomes play an important role by carrying extracellular nucleic acids (DNA, RNA) in cell-to-cell communication causing tumor and metastasis development. We discuss the role of extracellular vesicles in the pathogenesis of cancer and their practical application in the early diagnosis, follow up, and next-generation treatment of cancer patients.     

Kynurenic Acid and Its Analog SZR104 Exhibit Strong Antiinflammatory Effects and Alter the Intracellular Distribution and Methylation Patterns of H3 Histones in Immunochallenged Microglia-Enriched Cultures of Newborn Rat Brains

Kynurenic acid (KYNA) is implicated in antiinflammatory processes in the brain through several cellular and molecular targets, among which microglia-related mechanisms are of paramount importance. In this study, we describe the effects of KYNA and one of its analogs, the brain-penetrable SZR104 (N-(2-(dimethylamino)ethyl)-3-(morpholinomethyl)-4-hydroxyquinoline-2-carboxamide), on the intracellular distribution and methylation patterns of histone H3 in immunochallenged microglia cultures. Microglia-enriched secondary cultures made from newborn rat forebrains were immunochallenged with lipopolysaccharide (LPS). The protein levels of selected inflammatory markers C–X–C motif chemokine ligand 10 (CXCL10) and C–C motif chemokine receptor 1 (CCR1), histone H3, and posttranslational modifications of histone H3 lys methylation sites (H3K9me3 and H3K36me2, marks typically associated with opposite effects on gene expression) were analyzed using quantitative fluorescent immunocytochemistry and western blots in control or LPS-treated cultures with or without KYNA or SZR104. KYNA and SZR104 reduced levels of the inflammatory marker proteins CXCL10 and CCR1 after LPS-treatment. Moreover, KYNA and SZR104 favorably affected histone methylation patterns as H3K9me3 and H3K36me2 immunoreactivities, and histone H3 protein levels returned toward control values after LPS treatment. The cytoplasmic translocation of H3K9me3 from the nucleus indicated inflammatory distress, a process that could be inhibited by KYNA and SZR104. Thus, KYNA signaling and metabolism, and especially brain-penetrable KYNA analogs such as SZR104, could be key targets in the pathway that connects chromatin structure and epigenetic mechanisms with functional consequences that affect neuroinflammation and perhaps neurodegeneration.     

Phenolics of Vaccinium berries and other fruit crops

The concentrations and profiles of phenolics of selected fruit crops common in the Western diet, including several Vaccinium species, were examined to better understand how these crops may be useful sources of phenolic phytochemicals. Vaccinium fruit had a high phenolic concentration compared to non‐Vaccinium fruit. Some Vaccinium fruit were particularly rich in certain phenolic subgroups, especially anthocyanins and pro‐anthocyanidins. Among the pro‐anthocyanidin oligomers measured using fluorometric and mass spectroscopic detection, the trimers and tetramers were most abundant, while pro‐anthocyanidins with a degree of polymerization greater than 8 were least abundant. As biomedical studies determine which phenolic structures are associated with particular bioactivities, information on the phenolic concentration and profile of selected species will be useful in developing specific uses for fruit crops in human health. Methods were compared to assess the usefulness of simpler versus more sophisticated means of phenolic analysis. The phenolic components of fruit extracts were purified approximately 20‐fold, and not qualitatively altered, by C18 solid‐phase extraction. However, fruit extracts obtained from C18 solid‐phase extraction differed in their relative abundance of phenolic components. Colorimetric and HPLC‐DAD measures of phenolic concentration were correlated (R² = 0.79), as was pro‐anthocyanidin concentration detected fluorometrically and by mass spectrometry (R² = 0.44). Copyright © 2007 Crown in the right of Canada and Society of Chemical Industry     

Embedding RhPx in N,P Co‐Doped Carbon Nanoshells Through Synergetic Phosphorization and Pyrolysis for Efficient Hydrogen Evolution

Rational design and controllable synthesis of well‐defined nanostructures with high stability and Pt‐like activity for hydrogen evolution reaction (HER) are critical for renewable energy conversion. Herein, a unique pyrolysis strategy is demonstrated for the synthesis of RhP_x nanoparticles (NPs) in N, P co‐doped thin carbon nanoshells (RhP_x@NPC nanoshells) that display high electrocatalytic activity and stability over a wide pH range. This strategy involves simultaneous phosphorization and pyrolysis processes that can produce highly‐dispersed RhP_x NPs within N, P co‐doped carbon nanoshells and at the same time induce thinning of carbon nanoshells from inside out. The resulting RhP_x@NPC nanoshells not only possess Pt‐like activity for HER with low overpotentials to achieve 10 mA cm^?2 (22 mV in 0.5 m H₂SO₄, 69 mV in 1.0 m KOH, and 38 mV in 1.0 m phosphate buffered saline (PBS)) but also provide long‐term durability in a wide pH range. The remarkable HER performance of RhP_x@NPC nanoshells is ascribed to the high surface area, abundant mesoporosity, strong catalyst–support interaction, ultrathin carbon encapsulation, and N, P co‐doping. This work provides an effective strategy for designing heterostructured electrocatalysts with high catalytic activity and stability desired for reactions that may occur under harsh conditions.     

Pr-doped ZBLA fluoride glasses for visible laser emission

Praseodymium doped Fluoride glasses were studied in order to fabricate compact solid state laser sources emitting in the visible range for lighting application and for quantum information processing. The objective of this study is focused on red, green and orange emissions. ZBLA bulk glasses (57%ZrF₄ - 34%BaF₂ - (5 − x)%LaF₃ - 4%AlF₃ - x%PrF₃) have been synthesized under dry argon atmosphere. Physicochemical and optical properties such as density, glass transition temperature, composition, transmission and refractive index have been investigated. Spectroscopic studies have been performed to optimize the rare earth doping level in order to reach the best compromise respecting a good optical quality, a highest lifetime and efficient emission intensity at 635, 605 and 520 nm. Spectroscopic measurements have been carried out on bulk samples with Pr³⁺ concentrations ranging from 0.1 to 3 mol% and first characterizations of ion exchanged Pr: ZBLA waveguides are reported.     

Modeling the effects of yarn material properties and friction on the ballistic impact of a plain-weave fabric

Impact of a rigid sphere onto a high-strength plain-weave Kevlar KM2^® fabric was modeled using LS–DYNA^® focusing on the influence of friction and material properties on ballistic performance. Quasi-static friction was experimentally determined and incorporated into the model. Two clamped edges and two free edges were used as boundary conditions to correlate the model to an experimental test providing yarn–yarn movement. Yarns were modeled as continua with modulus and strength dominating along the length. Parametric studies incorporating different yarn material properties and initial projectile velocities were then performed with the above set of boundary conditions. Results indicate that ballistic performance depends upon friction, elastic modulus and strength of the yarns. While friction improves ballistic performance by maintaining the integrity of the weave pattern, material properties of the yarns have a significant influence on the effect of friction. It is shown that fabrics comprised of yarns characterized by higher stiffness and strength relative to the baseline Kevlar KM2^®, exhibited a stronger influence on ballistic performance. Therefore all three parameters viz., friction, elastic modulus and strength along with other variables (fabric architecture, boundary conditions, and projectile parameters) are needed to examine ballistic performance of high-strength fabric structures.     

Artistic collaboration in designing VR visualizations

This article describes one of the recent major collaborative efforts, a class on designing VR scientific visualizations that was co-taught with professors and students from Brown University's computer science department and the Rhode Island School of Design's (RISD's) illustration department. We discuss here the experiences that led us to this conclusion; along with some of the tools we have developed to facilitate working with artists. Many of the experiences and conclusions relayed here are the results of this class. We then discuss three important themes that we derived from our experiences, which are all motivated by a desire to better facilitate artistic collaborations.