Rheokinematics for product development—Formulation screening in rotational rheometers

Product formulations for industrial processes are typically developed at laboratory scale. However, the mixing conditions are not easily mimicked in the laboratory. A rotational device is proposed in this study as a fast laboratory-scale formulation development, which enables mimicking the mixing conditions in the industrial process. The geometrical configurations of the rotational device are from rheometry devices (plate-plate and cone-plate). The main advantages of this method are the small amounts of raw materials and shorter testing times. This methodology is applied to an industrial case study, the reaction injection molding (RIM) process. The mixing length scales evolution in the rotational rheometer were matched to those in RIM machines. The main novelty of this study is the introduction of a protocol that bridges the processing conditions at laboratory using small amounts of raw materials to high throughput continuous flow reactors.     

Applications of analytical electron microscopy to guide the design of boron carbide

Compositional analysis of boron carbide on nanometer length scales to examine or interpret atomic mechanisms, for example, solid-state amorphization or grain-boundary segregation, is challenging. This work reviews advancements in high-resolution microanalysis to characterize multiple generations of boron carbide. First, ζ-factor microanalysis will be introduced as a powerful (scanning) transmission electron microscopy ((S)TEM) analytical framework to accurately characterize boron carbide. Three case studies involving the application of ζ-factor microanalysis will then be presented: (1) accurate stoichiometry determination of B-doped boron carbide using ζ-factor microanalysis and electron energy loss spectroscopy, (2) normalized quantification of silicon grain-boundary segregation in Si-doped boron carbide, and (3) calibration of a scanning electron microscope X-ray energy-dispersive spectroscopy (XEDS) system to measure compositional homogeneity differences of B/Si-doped arc-melted boron carbides in the as-melted and annealed conditions. Overall, the improvement and application of advanced analytical tools have helped better understand processing–microstructure–property relationships and successfully manufacture high-performance ceramics.     

Aluminium-doped TiO2 nanotubes with enhanced light-harvesting properties

Titanium dioxide (TiO₂) application in light-harvesting processes is hindered by its wide band gap. Strategies such as morphology shifts from nanoparticles to nanotubes and doping of fabricated nanostructures are widely used to address this issue. Combining both approaches, this work successfully synthesizes, for the first time, aluminium-doped TiO₂ nanotubes via a single-step anodization method at three distinct potentials (20, 40 and 60 V). SEM images revealed the successful formation of remarkably thin layers of TiO₂ nanotubes produced at 40 and 60 V. X-ray diffractograms and Raman spectra suggest the successful insertion of aluminium into the anatase lattice. Diffuse reflectance confirmed the doping process through a marked effect on the absorbance of visible light for the higher voltages, as well as through a reduction in the optical band gap. For utilization purposes, the photoelectrochemical performance of 40 V Al–TiO₂ was able to deliver a comparable response to that of a compact TiO₂ layer of the same thickness. The current density developed by the 60 V sample was increased by 120% in comparison to the undoped material, despite having an absorbance much lower than that of the latter. Overall, synthesizing an Al-doped TiO₂ nanotubular structure has proven to be a great strategy in the development of materials for application in advanced light-harvesting electrodes.     

Design,Synthesis, and in vitro Evaluation of Tubulin-Targeting Dibenzothiazines with Antiproliferative Activity as a Novel Heterocycle Building Block

We prepared a series of free NH and N-substituted dibenzonthiazines with potential anti-tumor activity from N-aryl-benzenesulfonamides. A biological test of synthesized compounds (59 samples) was performed in vitro measuring their antiproliferative activity against a panel of six human solid tumor cell lines and its tubulin inhibitory activity. We identified 6-(phenylsulfonyl)-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide and 6-tosyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide as the best compounds with promising values of activity (overall range of 2–5.4 μM). Herein, we report the dibenzothiazine core as a novel building block with antiproliferative activity, targeting tubulin dynamics.     

Lamin-Related Congenital Muscular Dystrophy Alters Mechanical Signaling and Skeletal Muscle Growth

Laminopathies are a clinically heterogeneous group of disorders caused by mutations in the LMNA gene, which encodes the nuclear envelope proteins lamins A and C. The most frequent diseases associated with LMNA mutations are characterized by skeletal and cardiac involvement, and include autosomal dominant Emery–Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy type 1B, and LMNA-related congenital muscular dystrophy (LMNA-CMD). Although the exact pathophysiological mechanisms responsible for LMNA-CMD are not yet understood, severe contracture and muscle atrophy suggest that mutations may impair skeletal muscle growth. Using human muscle stem cells (MuSCs) carrying LMNA-CMD mutations, we observe impaired myogenic fusion with disorganized cadherin/β catenin adhesion complexes. We show that skeletal muscle from Lmna-CMD mice is unable to hypertrophy in response to functional overload, due to defective fusion of activated MuSCs, defective protein synthesis and defective remodeling of the neuromuscular junction. Moreover, stretched myotubes and overloaded muscle fibers with LMNA-CMD mutations display aberrant mechanical regulation of the yes-associated protein (YAP). We also observe defects in MuSC activation and YAP signaling in muscle biopsies from LMNA-CMD patients. These phenotypes are not recapitulated in closely related but less severe EDMD models. In conclusion, combining studies in vitro, in vivo, and patient samples, we find that LMNA-CMD mutations interfere with mechanosignaling pathways in skeletal muscle, implicating A-type lamins in the regulation of skeletal muscle growth.     

Human DDX17 Unwinds Rift Valley Fever Virus Non-Coding RNAs

Rift Valley fever virus (RVFV) is a mosquito-transmitted virus from the Bunyaviridae family that causes high rates of mortality and morbidity in humans and ruminant animals. Previous studies indicated that DEAD-box helicase 17 (DDX17) restricts RVFV replication by recognizing two primary non-coding RNAs in the S-segment of the genome: the intergenic region (IGR) and 5′ non-coding region (NCR). However, we lack molecular insights into the direct binding of DDX17 with RVFV non-coding RNAs and information on the unwinding of both non-coding RNAs by DDX17. Therefore, we performed an extensive biophysical analysis of the DDX17 helicase domain (DDX17_135–555) and RVFV non-coding RNAs, IGR and 5’ NCR. The homogeneity studies using analytical ultracentrifugation indicated that DDX17_135–555, IGR, and 5’ NCR are pure. Next, we performed small-angle X-ray scattering (SAXS) experiments, which suggested that DDX17 and both RNAs are homogenous as well. SAXS analysis also demonstrated that DDX17 is globular to an extent, whereas the RNAs adopt an extended conformation in solution. Subsequently, microscale thermophoresis (MST) experiments were performed to investigate the direct binding of DDX17 to the non-coding RNAs. The MST experiments demonstrated that DDX17 binds with the IGR and 5’ NCR with a dissociation constant of 5.77 ± 0.15 µM and 9.85 ± 0.11 µM, respectively. As DDX17_135–555 is an RNA helicase, we next determined if it could unwind IGR and NCR. We developed a helicase assay using MST and fluorescently-labeled oligos, which suggested DDX17_135–555 can unwind both RNAs. Overall, our study provides direct evidence of DDX17_135–555 interacting with and unwinding RVFV non-coding regions.     

Engineering Silver-Enriched Copper Core-Shell Electrocatalysts to Enhance the Production of Ethylene and C2+ Chemicals from Carbon Dioxide at Low Cell Potentials

Copper catalysts are widely studied for the electroreduction of carbon dioxide (CO₂) to value-added hydrocarbon products. Controlling the surface composition of copper nanomaterials may provide the electronic and structural properties necessary for carbon-carbon coupling, thus increasing the Faradaic efficiency (FE) towards ethylene and other multi-carbon (C₂₊) products. Synthesis and catalytic study of silver-coated copper nanoparticles (Cu@Ag NPs) for the reduction of CO₂ are presented. Bimetallic CuAg NPs are typically difficult to produce due to the bulk immiscibility between these two metals. Slow injection of the silver precursor, concentrations of organic capping agents, and gas environment proved critical to control the size and metal distribution of the Cu@Ag NPs. The optimized Cu@Ag electrocatalyst exhibited a very low onset cell potential of −2.25 V for ethylene formation, reaching a FE towards C₂₊ products (FE_C2+) of 43% at −2.50 V, which is 1.0 V lower than a reference Cu catalyst to reach a similar FE_C2+. The high ethylene formation at low potentials is attributed to enhanced C C coupling on the Ag enriched shell of the Cu@Ag electrocatalysts. This study offers a new catalyst design towards increasing the efficiency for the electroreduction of CO₂ to value-added chemicals.     

Sampling of Volatiles in Closed Systems: A Controlled Comparison of Three Solventless Volatile Collection Methods

Journal of Chemical Ecology - Complex inter-organismal communication among plants, insects, and microbes in natural and agricultural ecological systems is typically governed by emitted and...     

Cyclophilin Inhibition Protects Against Experimental Acute Kidney Injury and Renal Interstitial Fibrosis

Cyclophilins have important homeostatic roles, but following tissue injury, cyclophilin A (CypA) can promote leukocyte recruitment and inflammation, while CypD can facilitate mitochondrial-dependent cell death. This study investigated the therapeutic potential of a selective cyclophilin inhibitor (GS-642362), which does not block calcineurin function, in mouse models of tubular cell necrosis and renal fibrosis. Mice underwent bilateral renal ischemia/reperfusion injury (IRI) and were killed 24 h later: treatment with 10 or 30 mg/kg/BID GS-642362 (or vehicle) began 1 h before surgery. In the second model, mice underwent unilateral ureteric obstruction (UUO) surgery and were killed 7 days later; treatment with 10 or 30 mg/kg/BID GS-642362 (or vehicle) began 1 h before surgery. GS-642362 treatment gave a profound and dose-dependent protection from acute renal failure in the IRI model. This protection was associated with reduced tubular cell death, including a dramatic reduction in neutrophil infiltration. In the UUO model, GS-642362 treatment significantly reduced tubular cell death, macrophage infiltration, and renal fibrosis. This protective effect was independent of the upregulation of IL-2 and activation of the stress-activated protein kinases (p38 and JNK). In conclusion, GS-642362 was effective in suppressing both acute kidney injury and renal fibrosis. These findings support further investigation of cyclophilin blockade in other types of acute and chronic kidney disease.     

A Potent,Selective CBX2 Chromodomain Ligand and Its Cellular Activity During Prostate Cancer Neuroendocrine Differentiation

Polycomb group (PcG) proteins are epigenetic regulators that facilitate both embryonic development and cancer progression. PcG proteins form Polycomb repressive complexes 1 and 2 (PRC1 and PRC2). PRC2 trimethylates histone H3 lysine 27 (H3K27me3), a histone mark recognized by the N-terminal chromodomain (ChD) of the CBX subunit of canonical PRC1. There are five PcG CBX paralogs in humans. CBX2 in particular is upregulated in a variety of cancers, particularly in advanced prostate cancers. Using CBX2 inhibitors to understand and target CBX2 in prostate cancer is highly desirable; however, high structural similarity among the CBX ChDs has been challenging for developing selective CBX ChD inhibitors. Here, we utilize selections of focused DNA encoded libraries (DELs) for the discovery of a selective CBX2 chromodomain probe, SW2_152F. SW2_152F binds to CBX2 ChD with a K_d of 80 nM and displays 24-1000-fold selectivity for CBX2 ChD over other CBX paralogs in vitro. SW2_152F is cell permeable, selectively inhibits CBX2 chromatin binding in cells, and blocks neuroendocrine differentiation of prostate cancer cell lines in response to androgen deprivation.