Self-Assembled Bimetallic Aluminum-Salen Catalyst for the Cyclic Carbonates Synthesis.

Bimetallic bis-urea functionalized salen-aluminum catalysts have been developed for cyclic carbonate synthesis from epoxides and CO2. The urea moiety provides a bimetallic scaffold through hydrogen bonding, which expedites the cyclic carbonate formation reaction under mild reaction conditions. The turnover frequency (TOF) of the bis-urea salen Al catalyst is three times higher than that of a µ-oxo-bridged catalyst, and 13 times higher than that of a monomeric salen aluminum catalyst. The bimetallic reaction pathway is suggested based on urea additive studies and kinetic studies. Additionally, the X-ray crystal structure of a bis-urea salen Ni complex supports the self-assembly of the bis-urea salen metal complex through hydrogen bonding.

Surface Self-Assembly, Film Morphology, and Charge Transport Properties of Semiconducting Triazoloarenes.

Surface-assisted molecular self-assembly is a powerful strategy for forming molecular-scale architectures on surfaces. These molecular self-assemblies have potential applications in organic electronics, catalysis, photovoltaics, and many other technologies. Understanding the intermolecular interactions on a surface can help predict packing, stacking, and charge transport properties of films and allow for new molecular designs to be tailored for a required function. We have previously studied a molecular platform, tris( N-phenyltriazole) (TPT), that exhibits planar stacking through >20 molecular layers through donor-acceptor-type intermolecular π-π contacts between the electron-deficient tris(triazole) core and electron-rich peripheral phenyl units. Here, we investigate an expanded family of TPT-based molecules with variations made on the peripheral aryl groups to modulate the molecular electron distribution and examine the impact on molecular packing and charge transport properties. Molecular-resolution scanning tunneling microscopy was used to compare the molecular packing in the monolayer and to investigate the effects that the structural and electronic modifications have on the stacking in subsequent layers. Conductivity measurements were made using the four-point probe van der Pauw technique to demonstrate charge transport properties comparable to pentacene. Although molecular packing is clearly impacted by the chemical structure, we find that the charge transport efficiency is quite tolerant to small structural variations.

Redox-Driven Folding, Unfolding, and Refolding of Bis(tetrathiafulvalene) Molecular Switch.

We report redox-driven folding, unfolding, and refolding motions of a synthetic molecular system, in which two tetrathiafulvalene (TTF) units are tethered onto a conformationally rigid yet torsionally flexible π-conjugated backbone. Upon one-electron oxidation, this molecular switch undergoes swiveling motions from a fully relaxed and freely rotating Z-shaped conformation to a compact folded conformation stabilizing π-stacked radical species. Subsequent one-electron oxidation produces dicationic intermediates, which either engage in intimate π-π interactions or transition to an open structure. Further oxidation, however, brings the molecule back to the initial conformation to minimize the repulsion between doubly-charged TTF units. Intriguingly, the reaction coordinates of this redox-driven structural change have strong dependence on the environment, such as the solvent (THF vs CH2Cl2) and supporting electrolyte (PF6- vs B(C6F5)4-). With a proper design, factors that are typically considered as "secondary effects" could dictate the solution dynamics and reaction pathways of structural folding and unfolding, all driven by controlled delivery of electrons.

Massive parallel sequencing of short tandem repeats in the Korean population.

STR analysis using capillary electrophoresis has been the most widely used method for forensic DNA typing. Recently, massive parallel sequencing (MPS) technique has been emerging as an innovative tool to supplement or replace the conventional CE process. In this study, we evaluated the application of commercial MiSeqFGx™ forensic signature kit (Illumina Inc., San Diego, CA, USA) in the Korean population, including performance comparison with CE-based STR profiling kits. The genotyping results of 209 unrelated random Korean individuals were summarized according to the International Society for Forensic Genetics guideline. The study revealed that 26 novel sequence variations in autosomal STR were newly found that had not been previously reported in other forensic literature. This indicates that MPS may be an effective supplementary tool for forensic DNA typing and the database to increase the discriminatory power of individual identification.

Interactions between brush-grafted nanoparticles within chemically identical homopolymers: the effect of brush polydispersity.

We systematically examined the polymer-mediated interparticle interactions between polymer-grafted nanoparticles (NPs) within chemically identical homopolymer matrices through experimental and computational efforts. In experiments, we prepared thermally stable gold NPs grafted with polystyrene (PS) or poly(methyl methacrylate) (PMMA), and they were mixed with corresponding homopolymers. The nanocomposites are well dispersed when the molecular weight ratio of free to grafted polymers, α, is small. For α above 10, NPs are partially aggregated or clumped within the polymer matrix. Such aggregation of NPs at large α has been understood as an autophobic dewetting behavior of free homopolymers on brushes. In order to theoretically investigate this phenomenon, we calculated two particle interaction using self-consistent field theory (SCFT) with our newly developed numerical scheme, adopting two-dimensional finite volume method (FVM) and multi-coordinate-system (MCS) scheme which makes use of the reflection symmetry between the two NPs. By calculating the polymer density profile and interparticle potential, we identified the effects of several parameters such as brush thickness, particle radius, α, brush chain polydispersity, and chain end mobility. It was found that increasing α is the most efficient method for promoting autophobic dewetting phenomenon, and the attraction keeps increasing up to α = 20. At small α values, high polydispersity in brush may completely nullify the autophobic dewetting, while at intermediate α values, its effect is still significant in that the interparticle attractions are heavily reduced. Our calculation also revealed that the grafting type is not a significant factor affecting the NP aggregation behavior. The simulation result qualitatively agrees with the dispersion/aggregation transition of NPs found in our experiments.

Hypoxia-Responsive 19F MRI Probes with Improved Redox Properties and Biocompatibility.

19F magnetic resonance imaging (MRI), an emerging modality in biomedical imaging, has shown promise for in vitro and in vivo preclinical studies. Here we present a series of fluorinated Cu(II)ATSM derivatives for potential use as 19F magnetic resonance agents for sensing cellular hypoxia. The synthesized complexes feature a hypoxia-targeting Cu2+ coordination core, nine equivalent fluorine atoms connected via a variable-length poly(ethylene glycol) linker. Introduction of the fluorine moiety maintains the planar coordination geometry of the Cu2+ center, while the linker length modulates the Cu2+/+ reduction potential, 19F NMR relaxation properties, and lipophilicity. In particular, the 19F NMR relaxation properties were quantitatively evaluated by the Solomon-Bloembergen model, revealing a regular pattern of relaxation enhancement tuned by the distance between Cu2+ and F atoms. Finally, the potential utility of these complexes for sensing reductive environments was demonstrated using both 19F MR phantom imaging and 19F NMR, including experiments in intact live cells.

Differential pre-amplification of STR loci for fragmented forensic DNA profiling.

DNA profiling of short tandem repeats (STR) has been successfully used for the identification of individuals in forensic samples, accidents and natural disasters. However, STR profiling of DNA isolated from old crime scenes and damaged biological samples is difficult due to DNA degradation and fragmentation. Here, we show that pre-amplification of STR loci using biotinylated primers for the STR loci is an efficient strategy to obtain STR profiling results from fragmented forensic samples. Analysis of STR loci with longer amplicon sizes is generally hampered, since these relatively long loci are vulnerable to DNA fragmentation. This problem was overcome by using reduced or increased primer concentrations for loci with shorter or longer amplicon sizes, respectively, in our pre-amplification strategy. In addition, pre-amplification of STR loci into two groups of short or long amplicon size increases the efficiency of STR profiling from highly fragmented forensic DNA samples. Therefore, differential pre-amplification of STR loci is an effective way to obtain DNA profiling results from fragmented forensic samples.

SH3RF2 functions as an oncogene by mediating PAK4 protein stability.

SH3RF (SH3-domain-containing RING finger protein) family members, SH3RF1-3, are multidomain scaffold proteins involved in promoting cell survival and apoptosis. In this report, we show that SH3RF2 is an oncogene product that is overexpressed in human cancers and regulates p21-activated kinase 4 (PAK4) protein stability. Immunohistochemical analysis of 159 colon cancer tissues showed that SH3RF2 expression levels are frequently elevated in cancer tissues and significantly correlate with poor prognostic indicators, including increased invasion, early recurrence and poor survival rates. We also demonstrated that PAK4 protein is degraded by the ubiquitin-proteasome system and that SH3RF2 inhibits PAK4 ubiquitination via physical interaction-mediated steric hindrance, which results in the upregulation of PAK4 protein. Moreover, ablation of SH3RF2 expression attenuates TRADD (TNFR-associated death domain) recruitment to tumor necrosis factor-α (TNF-α) receptor 1 and hinders downstream signals, thereby inhibiting NF-κB (nuclear factor-kappaB) activity and enhancing caspase-8 activity, in the context of TNF-α treatment. Notably, ectopic expression of SH3RF2 effectively prevents apoptosis in cancer cells and enhances cell migration, colony formation and tumor growth in vivo. Taken together, our results suggest that SH3RF2 is an oncogene that may be a definitive regulator of PAK4. Therefore, SH3RF2 may represent an effective therapeutic target for cancer treatment.

Optimization of STR locus enrichment for STR profiling of fragmented DNA.

DNA degradation is a major obstacle in gaining an accurate profile with standard DNA typing technology. Although alternative genotyping strategies such as mini-STRs and SNPs have proven to be more successful in profiling degraded DNA, these approaches also have limitations. Here, we show that locus enrichment by hybridization of degraded genomic DNA with an STR locus-specific biotinylated oligonucleotide is a powerful approach to overcome problems in STR typing of highly degraded DNA. An experimental investigation of factors affecting the efficiency of this method indicates that the choice of primer and molar ratio of primers to genomic DNA are critical factors in improving enrichment of the STR locus before genotyping with multiplex kits. In addition, we find that indirect capture rather than direct capture with magnetic beads yields better enrichment efficiency for STR locus enrichments. Using these strategies, we demonstrate an improvement in STR typing of DNA from cultured cells damaged by exposure to sunlight or UV. We suggest that this approach could be applied to highly degraded forensic samples alone or in combination with mini-STRs.

High-fidelity self-assembly of crystalline and parallel-oriented organic thin films by π-π stacking from a metal surface.

Organic semiconductor applications will significantly benefit from atomically precise, cofacial stacking of extended π-conjugated molecular systems for efficient charge transport. Surface-assisted self-assembly of poly(hetero)cyclic molecules via donor-acceptor type π-π stacking is a promising strategy to organize functional, many-layered architectures. We have employed tris(N-phenyltriazole) as a model system to achieve molecular-level structural ordering through more than 20 molecular layers from its own metal-templated monolayer. Effective charge transport through such layers enabled molecular-resolution imaging by scanning tunneling microscopy. The structure and chemical composition of the films, grown on Ag(111) or Au(100), were further analyzed by noncontact atomic force microscopy and X-ray photoelectron spectroscopy, revealing a cofacial stacking geometry of the molecular layers. Scanning tunneling spectroscopy measurements show a decrease of the band gap with increasing film thickness, consistent with π-π stacking and electron delocalization. The present study provides new strategies for the fabrication of normally inaccessible structural motifs, atomic precision in organic films, and the effective conduction of electrons through multiple organic molecular stacks.

Target Discovery Using Deep Learning-Based Molecular Docking and Predicted Protein Structures With AlphaFold for Novel Antipsychotics.

OBJECTIVE: New drugs are needed to treat antipsychotic-resistant schizophrenia, especially those with clozapine-resistant schizophrenia. Atypical antipsychotics have predominantly 5-HT2A and dopaminergic antagonism, but also require investigation of other receptors. METHODS: In this study, the binding affinities between clozapine, olanzapine, and quetiapine with neuropharmacological, immunological, and metabolic receptors were measured using GNINA (Deep Learning Based Molecular Docking) and AlphaFold (Predicted Protein Structures). RESULTS: Through this study, it was determined that these antipsychotics showed high binding affinity to a variety of receptors, such as CB2, 5-HT1BR, NPYR4, and CCR5. Cyclosporin A and everolimus which show high affinities with those receptors could be used for the development of new antipsychotic drugs based on these drugs. CONCLUSION: In the future, the method used in this study will be applied to the development of new antipsychotic drugs, including drug repositioning, and to the discovery of the pathophysiology of schizophrenia.

Helical fluxionality: numerical frustration drives concerted low-barrier screw motions of a tricopper cluster.

Uneven allocation of resources creates frustration, tension, and conflicts. Confronted with an apparent mismatch between the number of donor atoms and the number of metal atoms to be supported, helically twisted ligands cleverly come up with a sustainable symbiotic solution. As an example, we present a tricopper metallohelicate exhibiting screw motions for intramolecular site exchange. A combination of X-ray crystallographic and solution NMR spectroscopic studies revealed thermo-neutral site exchange of three metal centres hopping back and forth inside the helical cavity lined by a spiral staircase-like arrangement of ligand donor atoms. This hitherto unknown helical fluxionality is a superimposition of translational and rotational movements of molecular actuation, taking the shortest path with an extraordinarily low energy barrier without compromising the overall structural integrity of the metal-ligand assembly.

Porous Crystalsomes via Emulsion Crystallization and Polymer Phase Separation.

Crystalsomes are crystalline capsules that are formed by controlling polymer crystallization to break translational symmetry. While recent studies showed that these crystalline capsules exhibit interesting mechanical properties, thermal behavior, and excellent performance in blood circulation, the closed capsule is undesired for drug delivery applications. We report the formation and characterization of porous crystalsomes where porosity is rendered on the crystalline shells. A miniemulsion is formed using two amphiphilic block copolymers (BCP). The competition between controlled crystallization and phase separation of the BCPs at the emulsion surface leads to multiphase crystalsomes. Subsequently removing one BCP produces porous crystalline capsules.

Insight on the Role of Poly(acrylic acid) for Directing Calcium Phosphate Mineralization of Synthetic Polymer Bone Scaffolds.

Bone is a complex tissue with robust mechanical and biological properties originating from its nanoscale composite structure. Although much research has been conducted on designing bioinspired artificial bone, the role of biological macromolecules such as noncollagenous proteins (NCPs) in influencing the formation of biominerals is not fully understood. In this work, we have designed nanofiber shish-kebab (NFSK) structures that can template mineral location by recruiting calcium cations from an ion-rich mineralization solution. Poly(acrylic acid) (PAA) is used as the NCP analogue to understand the role of polyelectrolytes in scaffold mineralization. We demonstrate that the addition of PAA in the mineralization solution suppresses the development of extrafibrillar minerals as well as slows down the accumulation and development of mineral phases within NFSKs. We probe the mechanism behind this effect by monitoring the free calcium ion concentration, investigating the PAA molecular weight effect, and conducting mineralization in membrane-partitioned solutions. Our results suggest the 2-fold effect of PAA as a solution stabilizer and physical barrier on the NFSK surface. This work could shed light on the understanding of the NCP effect in biomineralization.

MC3T3 E1 cell response to mineralized nanofiber shish kebab structures.

Block copolymers (BCPs) are of growing interest because of their extensive utility in tissue engineering, particularly in biomimetic approaches where multifunctionality is critical. We synthesized polycaprolactone-polyacrylic acid (PCL-b-PAA) BCP and crystallized it onto PCL nanofibers, making BCP nanofiber shish kebab (BCP NFSK) structures. When mineralized in 2× simulated body fluid, BCP NFSK mimic the structure of mineralized collagen fibrils. We hypothesized that the addition of a calcium phosphate layer of graded roughness on the nano-structure of the nanofiber shish kebabs would enhance preosteoblast alkaline phosphatase (ALP) activity, which has been shown to be a critical component in bone matrix formation. The objectives in the study were to investigate the effect of mineralization on cell proliferation and ALP activity, and to also investigate the effect of BCP NFSK periodicity, a structural feature describing the distance between PCL-b-PAA crystals on the nanofiber core, on cell proliferation, and ALP activity. ALP activity of cells cultured on the mineralized BCP NFSK template was significantly higher than the nonmineralized BCP NFSK templates. Interestingly, no statistical difference was observed in ALP activity when the periodic varied, indicating that surface chemistry seemed to play a larger role than the surface roughness.

Particulate Matter Exposure During Oocyte Maturation: Cell Cycle Arrest, ROS Generation, and Early Apoptosis in Mice.

Particulate matter (PM) is a general atmospheric pollutant released into the air by an anthropogenic and naturally derived mixture of substances. Current studies indicate that fine dust can result in different health defects, including endothelial dysfunction, asthma, lung cancer, cardiovascular diseases, uterine leiomyoma, deterioration in sperm quality, and overall birth impairment. However, the most prominent effects of PM10 (diameter < 10 µM) exposure on the female reproductive system, especially with respect to oocyte maturation, remain unclear. In the present study, maturing mouse oocytes were treated with PM10 and the phenotypes of the resulting toxic effects were investigated. Exposure to PM10 led to impairment of maturation capacity by inducing cell cycle arrest and blocking normal polar body extrusion during in vitro maturation and activation of fertilization of mouse oocytes. Additionally, defects in tubulin formation and DNA alignment were observed in PM10-treated oocytes during metaphase I to anaphase/telophase I transition. Moreover, PM10 induced reactive oxygen species generation, mitochondrial dysfunction, DNA damage, and early apoptosis. Taken together, these results indicate that PM10 exposure leads to a decline in oocyte quality and affects the subsequent embryonic development potential of mammalian oocytes.

2D MXene-containing polymer electrolytes for all-solid-state lithium metal batteries.

Nanocomposite polymer electrolytes (CPEs) are promising materials for all-solid-state lithium metal batteries (LMBs) due to their enhanced ionic conductivities and stability to the lithium anode. MXenes are a new two-dimensional, 2D, family of early transition metal carbides and nitrides, which have a high aspect ratio and a hydrophilic surface. Herein, using a green, facile aqueous solution blending method, we uniformly dispersed small amounts of Ti3C2T x into a poly(ethylene oxide)/LiTFSI complex (PEO20-LiTFSI) to fabricate MXene-based CPEs (MCPEs). The addition of the 2D flakes to PEO simultaneously retards PEO crystallization and enhances its segmental motion. Compared to the 0D and 1D nanofillers, MXenes show higher efficiency in ionic conductivity enhancement and improvement in the performance of LMBs. The CPE with 3.6 wt% MXene shows the highest ionic conductivity at room temperature (2.2 × 10-5 S m-1 at 28 °C). An LMB using MCPE with only 1.5 wt% MXene shows rate capability and stability comparable with that of the state-of-the-art CPELMBs. We attribute the excellent performance to the 2D geometry of the filler, the good dispersion of the flakes in the polymer matrix, and the functional group-rich surface.

Potential Applications of Non-thermal Plasma in Animal Husbandry to Improve Infrastructure.

Infrastructure in animal husbandry refers to fundamental facilities and services necessary for better living conditions of animals and its economy to function through better productivity. Mainly, infrastructure can be divided into two categories: hard infrastructure and soft infrastructure. Physical infrastructure, such as buildings, roads, and water supplying systems, belongs to hard infrastructure. Soft infrastructure includes services which are required to maintain economic, health, cultural and social standards of animal husbandry. Therefore, the proper management of infrastructure in animal husbandry is necessary for animal welfare and its economy. Among various technologies to improve the quality of infrastructure, non-thermal plasma (NTP) technology is an effectively applicable technology in different stages of animal husbandry. NTP is mainly helpful in maintaining better health conditions of animals in several ways via decontamination from microorganisms present in air, water, food, instruments and surfaces of animal farming systems. Furthermore, NTP is used in the treatment of waste water, vaccine production, wound healing in animals, odor-free ventilation, and packaging of animal food or animal products. This review summarizes the recent studies of NTP which can be related to the infrastructure in animal husbandry.

Block copolymer crystalsomes with an ultrathin shell to extend blood circulation time.

In water, amphiphilic block copolymers (BCPs) can self-assemble into various micelle structures depicting curved liquid/liquid interface. Crystallization, which is incommensurate with this curved space, often leads to defect accumulation and renders the structures leaky, undermining their potential biomedical applications. Herein we report using an emulsion-solution crystallization method to control the crystallization of an amphiphilic BCP, poly (L-lactide acid)-b-poly (ethylene glycol) (PLLA-b-PEG), at curved liquid/liquid interface. The resultant BCP crystalsomes (BCCs) structurally mimic the classical polymersomes and liposomes yet mechanically are more robust thanks to the single crystal-like crystalline PLLA shell. In blood circulation and biodistribution experiments, fluorophore-loaded BCCs show a 24 h circulation half-life and a 8% particle retention in the blood even at 96 h post injection. We further demonstrate that this good performance can be attributed to controlled polymer crystallization and the unique BCC nanostructure.

Conformationally Distorted π-Conjugation for Reaction-Based Detection of Nickel: Fluorescence Turn-on by Twist-and-Fragment.

A conformationally twisted N-arylbenzotriazole was designed as a fluorescence turn-on molecular probe. Under ambient conditions, metal-catalyzed deallylation reactions restore an intense blue emission. This reaction scheme is applicable exclusively to Group 10 transition metal ions and optimized, in particular, for nickel to allow sub-micromolar detection with no competition from other first-row transition-metal ions.