SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily A member 2 (SMARCA2), also known as Brahma homologue (BRM), is a Snf2-family DNA-dependent ATPase. BRM and its ...close homologue Brahma-related gene 1 (BRG1), also known as SMARCA4, are mutually exclusive ATPases of the large ATP-dependent SWI/SNF chromatin-remodeling complexes involved in transcriptional regulation of gene expression. No small molecules have been reported that modulate SWI/SNF chromatin-remodeling activity via inhibition of its ATPase activity, an important goal given the well-established dependence of BRG1-deficient cancers on BRM. Here, we describe allosteric dual BRM and BRG1 inhibitors that downregulate BRM-dependent gene expression and show antiproliferative activity in a BRG1-mutant-lung-tumor xenograft model upon oral administration. These compounds represent useful tools for understanding the functions of BRM in BRG1-loss-of-function settings and should enable probing the role of SWI/SNF functions more broadly in different cancer contexts and those of other diseases.
CuInxSeY/ZnS core/shell quantum dots are synthesized with an emission peak in the near IR and a high quantum yield, suitable for biomedical imaging in the optical window. After lipid coating and ...transferring to water, the quantum dots show good stability, retain their high quantum yield, and have relatively small sizes to optimize circulation and clearance post‐injection (P.I.).
Aim: We investigated the effects of metabolic syndrome (MetS) and its components, including a body shape index (ABSI), on increased arterial stiffness measured using the cardio-ankle vascular index ...(CAVI) according to sex and age strata.Methods: A total of 7127 asymptomatic Korean participants aged 21–90 years (men, 69.4%) were included. Age–sex-specific increased CAVI was defined as having the highest quartile of CAVI in each age group.Results: The CAVI increased with age and was higher in men. MetS was associated with an increased risk of high CAVI by 1.30 times in men and 1.45 times in women. The risk of high CAVI with an increasing MetS risk score was greater in women. MetS was significantly associated with increased CAVI in men only aged 51–70 years and in women aged ≥ 51 years, and the size of association increased with age (odds ratio (OR) of 1.41 in 51–70 years vs. OR of 2.96 in ≥ 71 years of women). Among MetS components, triglyceride (men, all ages), hypertension (men, 51–70 years; women, ≤ 70 years), glucose intolerance (men, 51–70 years; women, ≥ 51 years), and HDL-cholesterol (women, ≥ 71 years) were associated with increased CAVI.Unlike increased waist circumference (WC), increased ABSI revealed an association with high CAVI. MetS diagnosed with ABSI instead of WC was more significantly associated with increased CAVI in all age–sex groups. Conclusion: The association of MetS and its components with increased CAVI differed with age and sex, which might provide a new insight for the management of MetS risk factors to promote vascular health.
We present a facile method to enhance separation performance of polyamide (PA) reverse osmosis (RO) membranes via solvent activation with a new type of organic solvent, benzyl alcohol (BA). ...Activation with BA remarkably improved water permeance (up to ∼140% increase) while maintaining high NaCl rejection (∼99.6%) of the pristine RO membrane, thereby overcoming the flux-rejection trade-off limitation. Thus, the water permeance and permselectivity of the BA-activated RO membrane significantly exceeded those of commercial RO membranes. This significant performance enhancement was attributed to the appropriate solvency power of BA (determined based on Hansen solubility parameters), which led to the balanced structural deformation of the PA selective layer; BA activation produced a less dense and highly permeable PA structure by greatly swelling PA, while simultaneously healing loosened sites via structural compaction of the PA network with a sufficiently reduced modulus. Based on the activation results with various organic solvents ranging from mild to strong solvents, we propose a more reliable predictor of the solvent activation effect. Our strategy is a simple, effective and commercially viable method to enhance RO membrane performance. Additionally, our study highlights on the underlying solvent activating mechanism of PA RO membranes.
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•RO membranes were activated using benzyl alcohol (BA) to enhance their performance.•BA activation improved water flux (∼140% increase) without reducing NaCl rejection.•The BA-activated membrane greatly outperforms commercial RO membranes.•BA activation overcomes the flux-rejection trade-off limitation of RO membranes.•The appropriate solvency power of BA enables the effective performance enhancement.
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•TFC FO membranes are fabricated using aromatic organic solvents (toluene).•An ultrathin and highly dense PA layer was formed on a hydrophilic PAN support.•The prepared membranes show ...FO performance exceeding commercial membranes.•This is due to high permeability and excellent selectivity of the prepared membrane.•Aromatic solvent greatly promotes MPD diffusion by increased miscibility with water.
A high performance thin film composite (TFC) forward osmosis (FO) membrane was prepared using a hydrophilic polyacrylonitrile (PAN) support with a tailored structure via a newly devised, aromatic solvent (toluene)-based interfacial polymerization (TIP) technique. The use of toluene as the organic solvent promoted amine diffusion toward the organic phase and the subsequent reaction, leading to the formation of an ultrathin (highly permeable) and highly dense (highly selective) polyamide selective layer on the PAN support, which improved membrane performance. In addition, a relatively thin (∼80 μm) and finger-like porous support structure embedded with a nonwoven fabric was favorable for facilitating mass transport in the support. As a result, the TFC FO membrane prepared via TIP showed ∼2.1 times higher FO water flux and ∼68% lower specific salt flux than the membrane prepared via conventional aliphatic solvent-based interfacial polymerization (IP) in FO mode. Importantly, our TIP-assembled membrane exhibited superior FO performance over commercial and other lab-made membranes. Our strategy provides a facile solution to overcome the technical limitations of the conventional IP method by enabling the fabrication of high performance PA layers on hydrophilic supports, expanding the application spectrum of TFC membranes.
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Cancer-associated fibroblasts (CAFs) play a pivotal role in tumor growth, but very little has been known about its characteristics and origin. Recently, cancer-derived exosome has ...been suggested to transdifferentiate CAFs, by a new mechanism of endothelial to mesenchymal transition (EndMT), initiating angiogenic processes and triggering metastatic evolution. However, an enabling tool in vitro is yet to be developed to investigate complicated procedures of the EndMT and the transdifferentiation under reconstituted tumor microenvironment. Here we proposed an in vitro microfluidic model which enables to monitor a synergetic effect of complex tumor microenvironment in situ, including extracellular matrix (ECM), interstitial flow and environmental exosomes. The number of CAFs differentiated from human umbilical vein endothelial cells (HUVECs) increased with melanoma-derived exosomes, presenting apparent morphological and molecular changes with pronounced motility. Mesenchymal stem cell (MSC)-derived exosomes were found to suppress EndMT, induce angiogenesis and maintain vascular homeostasis, while cancer-derived exosomes promoted EndMT. Capabilities of the new microfluidic model exist in precise regulation of the complex tumor microenvironment and therefore successful reconstitution of 3D microvasculature niches, enabling in situ investigation of EndMT procedure between various cell types.
This study presents an in vitro 3D EndMT model to understand the progress of the CAF generation by recapitulating the 3D tumor microenvironment in a microfluidic device. Both cancer-derived exosomes and interstitial fluid flow synergetically played a pivotal role in the EndMT and consequent formation of CAFs through a collagen-based ECM. Our approach also enabled the demonstration of a homeostatic capability of MSC-derived exosomes, ultimately leading to the recovery of CAFs back to endothelial cells. The in vitro 3D EndMT model can serve as a powerful tool to validate exosomal components that could be further developed to anti-cancer drugs.
We report an aromatic solvent-assisted interfacial polymerization (IP) method to prepare high performance thin film composite reverse osmosis (RO) membranes based on a polyacrylonitrile support. The ...use of toluene and xylene as an organic solvent phase led to excellent water flux and unprecedentedly high NaCl rejection (∼99.9%), exceeding both the control membrane prepared using a conventional aliphatic solvent (n-hexane) and commercial RO membranes. The membrane prepared using n-hexane had a thick and moderately dense PA layer, due to the limited amine monomer diffusion, accounting for its relatively low performance. In contrast, the membranes fabricated using toluene/xylene had roof-like structures covering a thin and highly dense basal PA layer, which was formed by increased amine diffusion and an expanded miscible interface zone resulting from the enhanced miscibility of toluene/xylene with water. The excellent membrane performance achieved using toluene/xylene can be attributed to the thin and highly cross-linked basal PA layer.
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•TFC RO membranes are fabricated using aromatic organic solvents (toluene/xylene).•The prepared membranes show RO performance exceeding commercial membranes.•The prepared membranes exhibit unprecedentedly high NaCl rejection (∼99.9%).•Aromatic solvents greatly promote MPD diffusion by increased miscibility with water.•An ultrathin and highly dense PA layer is formed even on a hydrophilic PAN support.
Nitrogen-doped carbon-encapsulated non-noble metals are promising electrocatalytic alternatives to Pt for the oxygen reduction reaction (ORR). Herein, we describe the efficient synthesis of nitrogen- ...and fluorine-doped carbon-encapsulated Fe/Fe3C (NFC@Fe/Fe3C) crystals from a Fe-poly(aniline-fluoro-aniline) co-polymer and demonstrate their use as efficient ORR electrocatalysts in acidic and alkaline environments. X-ray diffraction patterns, scanning electron microscopy, transmission electron microscopy, Raman spectra, and X-ray photoelectron spectroscopy are used to determine the structural properties of NFC@Fe/Fe3C. Of the NFC@Fe/Fe3C catalysts, NFC@Fe/Fe3C-9 demonstrates superior ORR electrocatalytic activity in both alkaline and acidic environments. NFC@Fe/Fe3C-9 follows a four-electron-transfer ORR pathway in alkaline and acidic media. Under alkaline conditions, NFC@Fe/Fe3C-9 displays a half-wave potential (E1/2) as 0.870 V, which is 16 mV higher than that of Pt/C, and its durability decay is 26 mV over 50 000 cycles. In acidic medium, the NFC@Fe/Fe3C-9 electrode shows inferior ORR performance than does Pt/C, but it is more durable, with only 27 mV decay over 30 000 cycles. A single cell performance of NFC@Fe/Fe3C-9 was tested with a proton-exchange membrane fuel cells (PEMFC) and an anion-exchange membrane fuel cell (AEMFC) with an active area of 5 cm2. The PEMFC single cell exhibits the maximum power density of 237 mW cm−2 with a back pressure of 250 kPa, while the AEMFC delivers a maximum power density of 96 mW cm−2 without back pressure.
Delafossite CuFeO2 is a promising photocathode material for solar hydrogen production, but its performance is low because of poor charge transport properties. When the prepared CuFeO2 electrode is ...annealed by hybrid microwave annealing (HMA), its photoelectrochemical water reduction activity increases by more than 4 times (−1.3 mA cm–2 @ 0.4 VRHE), while the conventional thermal annealing (CTA) improves the performance by only 2 times (−0.62 mA cm–2 @0.4 VRHE). The postannealing of the electrode intercalates extra oxygen into the CuFeO2 lattice to form CuFeO2+1.5δ, which increases the charge carrier density and thus improves charge transport properties. The oxygen intercalation with HMA takes place more uniformly over the whole solid and is more effective than CTA. In addition, HMA post-treated CuFeO2 is modified with a NiFe-layered double hydroxide/reduced graphene oxide electrocatalyst, which exhibits a high photoactivity of −2.4 mA cm–2 @ 0.4 VRHE, unprecedented for CuFeO2-based photocathodes.
Osteoarthritis-the most common form of age-related degenerative whole-joint disease
-is primarily characterized by cartilage destruction, as well as by synovial inflammation, osteophyte formation and ...subchondral bone remodelling
. However, the molecular mechanisms that underlie the pathogenesis of osteoarthritis are largely unknown. Although osteoarthritis is currently considered to be associated with metabolic disorders, direct evidence for this is lacking, and the role of cholesterol metabolism in the pathogenesis of osteoarthritis has not been fully investigated
. Various types of cholesterol hydroxylases contribute to cholesterol metabolism in extrahepatic tissues by converting cellular cholesterol to circulating oxysterols, which regulate diverse biological processes
. Here we show that the CH25H-CYP7B1-RORα axis of cholesterol metabolism in chondrocytes is a crucial catabolic regulator of the pathogenesis of osteoarthritis. Osteoarthritic chondrocytes had increased levels of cholesterol because of enhanced uptake, upregulation of cholesterol hydroxylases (CH25H and CYP7B1) and increased production of oxysterol metabolites. Adenoviral overexpression of CH25H or CYP7B1 in mouse joint tissues caused experimental osteoarthritis, whereas knockout or knockdown of these hydroxylases abrogated the pathogenesis of osteoarthritis. Moreover, retinoic acid-related orphan receptor alpha (RORα) was found to mediate the induction of osteoarthritis by alterations in cholesterol metabolism. These results indicate that osteoarthritis is a disease associated with metabolic disorders and suggest that targeting the CH25H-CYP7B1-RORα axis of cholesterol metabolism may provide a therapeutic avenue for treating osteoarthritis.
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