Circular RNA circSMAD4 regulates cardiac fibrosis by targeting miR-671-5p and FGFR2 in cardiac fibroblasts.

Heart failure is a leading cause of death and is often accompanied by activation of quiescent cardiac myofibroblasts, which results in cardiac fibrosis. In this study, we aimed to identify novel circular RNAs that regulate cardiac fibrosis. We applied transverse aortic constriction (TAC) for 1, 4, and 8 weeks in mice. RNA sequencing datasets were obtained from cardiac fibroblasts isolated by use of a Langendorff apparatus and then further processed by use of selection criteria such as differential expression and conservation in species. CircSMAD4 was upregulated by TAC in mice or by transforming growth factor (TGF)-ß1 in primarily cultured human cardiac fibroblasts. Delivery of si-circSMAD4 attenuated myofibroblast activation and cardiac fibrosis in mice treated with isoproterenol (ISP). si-circSmad4 significantly reduced cardiac fibrosis and remodeling at 8 weeks. Mechanistically, circSMAD4 acted as a sponge against the microRNA miR-671-5p in a sequence-specific manner. miR-671-5p was downregulated during myofibroblast activation and its mimic form attenuated cardiac fibrosis. miR-671-5p mimic destabilized fibroblast growth factor receptor 2 (FGFR2) mRNA in a sequence-specific manner and interfered with the fibrotic action of FGFR2. The circSMAD4-miR-671-5p-FGFR2 pathway is involved in the differentiation of cardiac myofibroblasts and thereby the development of cardiac fibrosis.

Toughening self-healing elastomer crosslinked by metal-ligand coordination through mixed counter anion dynamics.

Mechanically tough and self-healable polymeric materials have found widespread applications in a sustainable future. However, coherent strategies for mechanically tough self-healing polymers are still lacking due to a trade-off relationship between mechanical robustness and viscoelasticity. Here, we disclose a toughening strategy for self-healing elastomers crosslinked by metal-ligand coordination. Emphasis was placed on the effects of counter anions on the dynamic mechanical behaviors of polymer networks. As the coordinating ability of the counter anion increases, the binding of the anion leads to slower dynamics, thus limiting the stretchability and increasing the stiffness. Additionally, multimodal anions that can have diverse coordination modes provide unexpected dynamicity. By simply mixing multimodal and non-coordinating anions, we found a significant synergistic effect on mechanical toughness ( > 3 fold) and self-healing efficiency, which provides new insights into the design of coordination-based tough self-healing polymers.

Morphology-Dependent Interaction of Silica Nanoparticles with Intestinal Cells: Connecting Shape to Barrier Function.

The intestinal compartment ensures nutrient absorption and barrier function against pathogens. Despite decades of research on the complexity of the gut, the adaptive potential to physical cues, such as those derived from interaction with particles of different shapes, remains less understood. Taking advantage of the technological versatility of silica nanoparticles, spherical, rod-shaped, and virus-like materials were synthesized. Morphology-dependent interactions were studied on differentiated Caco-2/HT29-MTX-E12 cells. Contributions of shape, aspect ratio, surface roughness, and size were evaluated considering the influence of the mucus layer and intracellular uptake pathways. Small particle size and surface roughness favored the highest penetration through the mucus but limited interaction with the cell monolayer and efficient internalization. Particles of a larger aspect ratio (rod-shaped) seemed to privilege paracellular permeation and increased cell-cell distances, albeit without hampering barrier integrity. Inhibition of clathrin-mediated endocytosis and chemical modulation of cell junctions effectively tuned these responses, confirming morphology-specific interactions elicited by bioinspired silica nanomaterials.

Hierarchical LTL Zeolite as an Efficient and Sustainable Solid Acid Catalyst for Replacing HCl in the Production of Polyurethane Intermediates.

In many industrially important reactions, caustic mineral acid catalysts have been successfully replaced with green solid acids such as zeolites. In this context, extensive efforts have been devoted to replacing HCl to produce methylenedianiline (MDA), a key intermediate in polyurethane production. Unfortunately, limited success has been achieved thus far due to low activity, selectivity towards the desired 4,4'-MDA, and rapid catalyst deactivation. Here we report that meso-/microporous hierarchical LTL zeolite exhibits unprecedentedly high activity, selectivity, and stability. The one-dimensional cage-like micropores of LTL promote the bimolecular reaction between two para-aminobenzylaniline intermediates to selectively produce 4,4'-MDA and inhibit the formation of undesired isomers and heavy oligomers. Meanwhile, the secondary mesopores alleviate mass transfer limitations, resulting in a 7.8-fold higher MDA formation rate compared to solely microporous LTL zeolite. Due to suppressed oligomer formation and fast mass transfer, the catalyst exhibits inappreciable deactivation in an industrially relevant continuous flow reactor.

Mercaptoamine-assisted Post-encapsulation of Metal Nanoparticles within Preformed Zeolites and their Analogues for Hydroisomerization and Methane Decomposition.

We report a general synthetic strategy for post-encapsulation of metal nanoparticles within preformed zeolites using post-synthetic modification. Both anionic and cationic precursors to metal nanoparticle are supported on 8- and 10-membered ring zeolites and analogues during wet impregnation using 2-aminoethanethiol (AET) as a bi-grafting agent. Thiol groups are coordinated to metal centers, whereas amine moieties are dynamically attached to micropore walls via acid-base interactions. The dynamic acid-base interactions cause the even distribution of the metal-AET complex throughout the zeolite matrix. These processes encapsulate Au, Rh, and Ni precursors within the CHA, *MRE, MFI zeolite, and SAPO-34 zeolite analogues, for which small channel apertures preclude the post-synthesis impregnation of metal precursors. Sequential activation forms small and uniform nanoparticles (1-2.5 nm in diameter), as confirmed through electron microscopy and X-ray absorption spectroscopy. Containment within the small micropores protected the nanoparticles against harsh thermal sintering conditions and prevented the fouling of the metal surface by coke, thus resulting in a high catalytic performance in n-dodecane hydroisomerization and methane decomposition. The remarkable specificity of the thiol to metal precursors and the dynamic acid-base interaction make these protocols extendable to various metal-zeolite systems, suitable for shape-selective catalysts in challenging chemical environments.

First successful synthesis of an Al-rich mesoporous aluminosilicate for fast radioactive strontium capture.

Al-rich zeolites such as NaA (Si/Al = 1.00) have been widely applied to remove radioactive 90Sr2+ because of their high surface charge density enabling efficient ion-exchange of multivalent cations. However, due to the small micropore diameters of zeolites and large molecular size of strongly hydrated Sr2+, Sr2+-exchange with zeolites suffers from very slow kinetics. In principle, mesoporous aluminosilicates with low Si/Al ratios close to unity and tetrahedrally coordinated Al sites can exhibit both high capacity and fast kinetics in Sr2+-exchange. Nonetheless, the synthesis of such materials has not been realized yet. In this study, we demonstrate the first successful synthesis of an Al-rich mesoporous silicate (ARMS) using a cationic organosilane surfactant as an efficient mesoporogen. The material exhibited a wormhole-like mesoporous structure with a high surface area (851 m2 g-1) and pore volume (0.77 cm3 g-1), and an Al-rich framework (Si/Al = 1.08) with most Al sites tetrahedrally coordinated. Compared to commercially applied NaA, ARMS exhibited a dramatically improved Sr2+-exchange kinetics (>33-fold larger rate constant) in batch adsorption while showing similarly high Sr2+ capture capacity and selectivity. Due to the fast Sr2+-exchange kinetics, the material also exhibited 3.3-fold larger breakthrough volume than NaA in fixed-bed continuous adsorption.

Confining Gold Nanoparticles in Preformed Zeolites by Post-Synthetic Modification Enhances Stability and Catalytic Reactivity and Selectivity.

Confining Au nanoparticles (NPs) in a restricted space (e.g., zeolite micropores) is a promising way of overcoming their inherent thermal instability and susceptibility to aggregation, which limit catalytic applications. However, such approaches involve complex, multistep encapsulation processes. Here, we describe a successful strategy and its guiding principles for confining small (<2 nm) and monodisperse Au NPs within commercially available beta and MFI zeolites, which can oxidize CO at 40 °C and show size-selective catalysis. This protocol involves post-synthetic modification of the zeolite internal surface with thiol groups, which confines AuCl x species inside microporous frameworks during the activation process whereby Au precursors are converted into Au nanoparticles. The resulting beta and MFI zeolites contain uniformly dispersed Au NPs throughout the void space, indicating that the intrinsic stability of the framework promotes resistance to sintering. By contrast, in situ scanning transmission electron microscopy (STEM) studies evidenced that Au precursors in bare zeolites migrate from the matrix to the external surface during activation, thereby forming large and poorly dispersed agglomerates. Furthermore, the resistance of confined Au NPs against sintering is likely relevant to the intrinsic stability of the framework, supported by extended X-ray absorption fine structure (EXAFS), H2 chemisorption, and CO Fourier transform infrared (FT-IR) studies. The Au NPs supported on commercial MFI maintain their uniform dispersity to a large extent after treatment at 700 °C that sinters Au clusters on mesoporous silicas or beta zeolites. Low-temperature CO oxidation and size-selective reactions highlight that most gold NPs are present inside the zeolite matrix with a diameter smaller than 2 nm. These findings illustrate how confinement favors small, uniquely stable, and monodisperse NPs, even for metals such as Au susceptible to cluster growth under conditions often required for catalytic use. Moreover, this strategy may be readily adapted to other zeolite frameworks that can be functionalized by thiol groups.

Postsynthetic Modification of Zeolite Internal Surface for Sustainable Capture of Volatile Organic Compounds under Humid Conditions.

Although low-cost, high-surface-area crystalline aluminosilicate zeolites have been recognized as promising adsorbents for the capture of volatile organic compounds (VOCs), their hydrophilic nature leads to a significant loss of performance owing to the ubiquitous presence of water vapor in the VOC stream. Herein, the aluminosilicate zeolites (i.e., mordenite and nanocrystalline ß) are functionalized via a solvothermal post-treatment with methyl iodide as the grafting agent. The methyl groups are primarily attached to the zeolite internal surface via covalent bonding between internal bridging O and -CH3, as evidenced by multiple analysis data. The static isotherms and diffusional studies clearly reveal a remarkable decrease in both the rate of water adsorption and the water affinity due to the attachment of methyl groups to the micropore walls, thus enhancing the water tolerance compared to that of pristine zeolites. In addition, CH3I-functionalized zeolites are investigated as adsorbents for the removal of benzene under dry and humid conditions, and their performance is compared to that of CH3Si(-OCH3)3-functionalized zeolites, wherein the methyl groups have been grafted onto the external surface. The results demonstrate that, although the benzene adsorption capacity under dry conditions is decreased upon internal surface functionalization, the loss of VOC adsorption capacity in the presence of H2O vapor is effectively prevented. By contrast, external surface functionalization is ineffective for preventing the negative effects of moisture upon the benzene adsorption capacity. As a result, CH3I-functionalized zeolites exhibit superior dynamic adsorption performance for benzene at 318 K under humid conditions (relative humidity: 80%), with a saturated adsorption capacity of 64.9 mg g-1. This work provides an easy strategy for tailoring the adsorption properties of aluminosilicate zeolites for adsorption/separation and other advanced applications.

Rare-earth-platinum alloy nanoparticles in mesoporous zeolite for catalysis.

Platinum is a much used catalyst that, in petrochemical processes, is often alloyed with other metals to improve catalytic activity, selectivity and longevity1-5. Such catalysts are usually prepared in the form of metallic nanoparticles supported on porous solids, and their production involves reducing metal precursor compounds under a H2 flow at high temperatures6. The method works well when using easily reducible late transition metals, but Pt alloy formation with rare-earth elements through the H2 reduction route is almost impossible owing to the low chemical potential of rare-earth element oxides6. Here we use as support a mesoporous zeolite that has pore walls with surface framework defects (called 'silanol nests') and show that the zeolite enables alloy formation between Pt and rare-earth elements. We find that the silanol nests enable the rare-earth elements to exist as single atomic species with a substantially higher chemical potential compared with that of the bulk oxide, making it possible for them to diffuse onto Pt. High-resolution transmission electron microscopy and hydrogen chemisorption measurements indicate that the resultant bimetallic nanoparticles supported on the mesoporous zeolite are intermetallic compounds, which we find to be stable, highly active and selective catalysts for the propane dehydrogenation reaction. When used with late transition metals, the same preparation strategy produces Pt alloy catalysts that incorporate an unusually large amount of the second metal and, in the case of the PtCo alloy, show high catalytic activity and selectivity in the preferential oxidation of carbon monoxide in H2.

Cascade reaction engineering on zirconia-supported mesoporous MFI zeolites with tunable Lewis-Brønsted acid sites: a case of the one-pot conversion of furfural to γ-valerolactone.

Catalytic cascade reactions are strongly desired as a potential means of combining multistep reactions into a single catalytic reactor. Appropriate catalysts composed of multi-reactive sites to catalyze cascade reactions in a sequential fashion are central to such efforts. Here, we demonstrate a bifunctional zeolite catalyst with close proximity of Brønsted and Lewis acid sites through the synthesis of a mesoporous ZrO2[Al]MFI nanosponge (NS). The unique mesopores of the MFI-NS allow the confinement of zirconium oxide clusters (Lewis acid sites, LA) within the few-unit-cell-thin MFI aluminosilicate zeolite wall (Brønsted acid sites, BA). Such a structure is clearly distinct from the conventional MFI zeolite, where the agglomeration of zirconium oxide clusters onto the external surface area within the crystal bulk is not possible, resulting in segregated BA and LA sites on the internal and external zeolite, respectively. By bringing the BA and LA within ZrO2[Al]MFI-NS 30, we uncovered a more efficient catalytic route for the conversion of furfural (100% within 2 h) to γ-valerolactone (GVL) (83%). This route is only evident when the long molecular diffusion path, in the most extreme case of physically mixed ZrO2-(LA) and Al-zeolites (BA) (45% of GVL yield), is eliminated. Unlike the bifunctional ZrO2-Al-beta (GVL yield of 75%), where the BA concentration is greatly compromised at the expense of LA formation, we also show that the ZrO2[Al]MFI-NS is able to maintain a high density and good stability of both types of acids.

Oct4 suppresses IR­induced premature senescence in breast cancer cells through STAT3- and NF­κB-mediated IL­24 production.

Breast cancer stem cells (BCSCs) are a small subpopulation of breast cancer cells that have been proposed to be a primary cause of failure of therapies, including ionizing radiation (IR). Their embryonic stem-like signature is associated with poor clinical outcome. In the present study, the function of octamer-binding transcription factor 4 (Oct4), an embryonic stem cell factor, in the resistance of BCSCs to IR was investigated. Mammosphere cells exhibited increased expression of stemness-associated genes, including Oct4 and sex­determining region Y­box 2 (Sox2), and were more resistant to IR compared with serum-cultured monolayer cells. IR­resistant MCF7 cells also exhibited significantly increased expression of Oct4. To investigate the possible involvement of Oct4 in IR resistance of breast cancer cells, cells were transfected with Oct4. Ectopic expression of Oct4 increased the clonogenic survival of MCF7 cells following IR, which was reversed by treatment with small interfering RNA (siRNA) targeting Oct4. Oct4 expression decreased phosphorylated histone H2AX (γ-H2AX) focus formation and suppressed IR­induced premature senescence in these cells. Mammosphere, IR­resistant and Oct4­overexpressing MCF7 cells exhibited enhanced phosphorylation of signal transducer and activation of transcription 3 (STAT3) (Tyr705) and inhibitor of nuclear factor κB (NF­κB), and blockade of these pathways with siRNA against STAT3 and/or specific inhibitors of STAT3 and NF­κB significantly increased IR­induced senescence. Secretome analysis revealed that Oct4 upregulated interleukin 24 (IL­24) expression through STAT3 and NF­κB signaling, and siRNA against IL­24 increased IR­induced senescence, whereas recombinant human IL­24 suppressed it. The results of the present study indicated that Oct4 confers IR resistance on breast cancer cells by suppressing IR­induced premature senescence through STAT3- and NF­κB-mediated IL­24 production.

Sumoylation of histone deacetylase 1 regulates MyoD signaling during myogenesis.

Sumoylation, the conjugation of a small ubiquitin-like modifier (SUMO) protein to a target, has diverse cellular effects. However, the functional roles of the SUMO modification during myogenesis have not been fully elucidated. Here, we report that basal sumoylation of histone deacetylase 1 (HDAC1) enhances the deacetylation of MyoD in undifferentiated myoblasts, whereas further sumoylation of HDAC1 contributes to switching its binding partners from MyoD to Rb to induce myocyte differentiation. Differentiation in C2C12 skeletal myoblasts induced new immunoblot bands above HDAC1 that were gradually enhanced during differentiation. Using SUMO inhibitors and sumoylation assays, we showed that the upper band was caused by sumoylation of HDAC1 during differentiation. Basal deacetylase activity was not altered in the SUMO modification-resistant mutant HDAC1 K444/476R (HDAC1 2R). Either differentiation or transfection of SUMO1 increased HDAC1 activity that was attenuated in HDAC1 2R. Furthermore, HDAC1 2R failed to deacetylate MyoD. Binding of HDAC1 to MyoD was attenuated by K444/476R. Binding of HDAC1 to MyoD was gradually reduced after 2 days of differentiation. Transfection of SUMO1 induced dissociation of HDAC1 from MyoD but potentiated its binding to Rb. SUMO1 transfection further attenuated HDAC1-induced inhibition of muscle creatine kinase luciferase activity that was reversed in HDAC1 2R. HDAC1 2R failed to inhibit myogenesis and muscle gene expression. In conclusion, HDAC1 sumoylation plays a dual role in MyoD signaling: enhancement of HDAC1 deacetylation of MyoD in the basally sumoylated state of undifferentiated myoblasts and dissociation of HDAC1 from MyoD during myogenesis.

Biomechanical Analysis of Normal Brain Development during the First Year of Life Using Finite Strain Theory.

The first year of life is the most critical time period for structural and functional development of the human brain. Combining longitudinal MR imaging and finite strain theory, this study aimed to provide new insights into normal brain development through a biomechanical framework. Thirty-three normal infants were longitudinally imaged using MRI from 2 weeks to 1 year of age. Voxel-wise Jacobian determinant was estimated to elucidate volumetric changes while Lagrange strains (both normal and shear strains) were measured to reveal directional growth information every 3 months during the first year of life. Directional normal strain maps revealed that, during the first 6 months, the growth pattern of gray matter is anisotropic and spatially inhomogeneous with higher left-right stretch around the temporal lobe and interhemispheric fissure, anterior-posterior stretch in the frontal and occipital lobes, and superior-inferior stretch in right inferior occipital and right inferior temporal gyri. In contrast, anterior lateral ventricles and insula showed an isotropic stretch pattern. Volumetric and directional growth rates were linearly decreased with age for most of the cortical regions. Our results revealed anisotropic and inhomogeneous brain growth patterns of the human brain during the first year of life using longitudinal MRI and a biomechanical framework.

Nomenclature for renal replacement therapy in acute kidney injury: basic principles.

This article reports the conclusions of a consensus expert conference on the basic principles and nomenclature of renal replacement therapy (RRT) currently utilized to manage acute kidney injury (AKI). This multidisciplinary consensus conference discusses common definitions, components, techniques, and operations of the machines and platforms used to deliver extracorporeal therapies, utilizing a "machine-centric" rather than a "patient-centric" approach. We provide a detailed description of the performance characteristics of membranes, filters, transmembrane transport of solutes and fluid, flows, and methods of measurement of delivered treatment, focusing on continuous renal replacement therapies (CRRT) which are utilized in the management of critically ill patients with AKI. This is a consensus report on nomenclature harmonization for principles of extracorporeal renal replacement therapies. Devices and operations are classified and defined in detail to serve as guidelines for future use of terminology in papers and research.

Con-Current versus Counter-Current Dialysate Flow during CVVHD. A Comparative Study for Creatinine and Urea Removal.

BACKGROUND: Dialysate fluid connection to the membrane in continuous dialysis may affect solute clearance. Although circuit connections are routinely made counter-current to blood flow in intermittent dialysis, no study has assessed the effect of this dialysate fluid flow direction on removal of small solutes creatinine and urea during treatment using continuous veno-venous haemodialysis (CVVHD). AIMS: To assess if dialysate flow direction during CVVHD affects small solute removal. METHODS: This ethics-approved study recruited a convenience sample of 26 adult ICU patients requiring continuous dialysis to assess urea and creatinine removal for con-current vs. counter-current dialysate flow direction. The circuit was adjusted from continuous veno-venous haemodiafiltration to CVVHD 20 min prior to sampling with no fluid removal. Blood (b) and spent dialysate fluid (f) were taken in both concurrent and counter-current fluid flow at 1 (T1) and 4 (T4) hours with a new treatment. Blood flow was 200 ml/min. Dialysate flow 33 ml/min. Removal of urea and creatinine was expressed as the diafiltrate/plasma concentration ratio: Uf/b and Cf/b respectively. Data lacking normal distribution are presented as median with 25th and 75th interquartile ranges (IQR), otherwise as mean with SD and assessed with the independent t test for paired data. p < 0.5 was considered significant. RESULTS: Fifteen male patients were included with a median (IQR) age of 67 years (52-75), and APACHE x0399;x0399; score 17 (14-19) with all patients meeting RIFLE criteria 'F'. At both times, the counter-current dialysate flow was associated with higher mean (SD) diafiltrate/plasma concentration ratios: T1 0.87 (0.16) vs. 0.77 (0.10), p = 0.006; T2 0.96 (0.16) vs. 0.76 (0.09), p < 0.001 for creatinine and T1 0.98 (0.09) vs. 0.81 (0.09), p < 0.001; T2 0.99 (0.07) vs. 0.82 (0.08), p < 0.001 for urea. CONCLUSION: Counter-current dialysate flow during CVVHD for ICU patients is associated with an approximately 20% increase in removal of small solutes creatinine and urea. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=441270.

In vitro Cytotoxicity of Bisphenol A in Monocytes Cell Line.

BACKGROUND/AIM: Bisphenol A (BPA) is used in the production of many plastics, which are used to build biomaterials that sometimes are in direct contact with blood. It is believed that the release of BPA into bloodstream may give rise to cytotoxic events for blood components. The aim of the present study was to perform an in vitro investigation of the observable cytotoxic effect of BPA, at increasing concentrations, on the monocyte cell line. METHODS: We incubated in vitro monocyte cells (U937) for 24 h in cell line medium samples (RPMI 1640) at different concentrations of BPA. We then generated curves to evaluate viability, necrosis and apoptosis of monocytes against increasing concentrations of BPA. RESULTS: The percentage values of concentrations of BPA corresponding to 50% of the viability and necrosis of the monocytes were 1.39 and 1.48 ng/ml, respectively. Based on our observations, we reported an increasing cytotoxic effect for higher concentrations. The apoptotic effect reached the maximum value at BPA concentration of 1.5 ng/ml; at still higher concentrations, we observed a predominantly necrotic cell death. CONCLUSION: Viability, necrosis and apoptosis of monocytes are strongly and positively correlated with BPA concentration. A direct contact of such compound with biological components of blood may lead to high levels of cytotoxicity, and require us to evaluate additional factors while judging the bio-incompatibility of BPA.

Cardiac surgery-associated acute kidney injury.

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious postoperative complication of cardiac surgery requiring cardiopulmonary bypass (CPB), and it is the second most common cause of AKI in the intensive care unit. Although the complication has been associated with the use of CPB, the etiology is likely multifactorial and related to intraoperative and early postoperative management including pharmacologic therapy. To date, very little evidence from randomized trials supporting specific interventions to protect from or prevent AKI in broad cardiac surgery populations has been found. The definition of AKI employed by investigators influences not only the incidence of CSA-AKI, but also the identification of risk variables. The advent of novel biomarkers of kidney injury has the potential to facilitate the subclinical diagnosis of CSA-AKI, the assessment of its severity and prognosis, and the early institution of interventions to prevent or reduce kidney damage. Further studies are needed to determine how to optimize cardiac surgical procedures, CPB parameters, and intraoperative and early postoperative blood pressure and renal blood flow to reduce the risk of CSA-AKI. No pharmacologic strategy has demonstrated clear efficacy in the prevention of CSA-AKI; however, some agents, such as the natriuretic peptide nesiritide and the dopamine agonist fenoldopam, have shown promising results in renoprotection. It remains unclear whether CSA-AKI patients can benefit from the early institution of such pharmacologic agents or the early initiation of renal replacement therapy.

Ret finger protein mediates Pax7-induced ubiquitination of MyoD in skeletal muscle atrophy.

Skeletal muscle atrophy results from the net loss of muscular proteins and organelles and is caused by pathologic conditions such as nerve injury, immobilization, cancer, and other metabolic diseases. Recently, ubiquitination-mediated degradation of skeletal-muscle-specific transcription factors was shown to be involved in muscle atrophy, although the mechanisms have yet to be defined. Here we report that ret finger protein (RFP), also known as TRIM27, works as an E3 ligase in Pax7-induced degradation of MyoD. Muscle injury induced by sciatic nerve transection up-regulated RFP and RFP physically interacted with both Pax7 and MyoD. RFP and Pax7 synergistically reduced the protein amounts of MyoD but not the mRNA. RFP-induced reduction of MyoD protein was blocked by proteasome inhibitors. The Pax7-induced reduction MyoD was attenuated by RFP siRNA and by MG132, a proteasome inhibitor. RFPΔR, an RFP construct that lacks the RING domain, failed to reduce MyoD amounts. RFP ubiquitinated MyoD, but RFPΔR failed to do so. Forced expression of RFP, but not RFPΔR, enhanced Pax7-induced ubiquitination of MyoD, whereas RFP siRNA blocked the ubiquitination. Sciatic nerve injury-induced muscle atrophy as well the reduction in MyoD was attenuated in RFP knockout mice. Taken together, our results show that RFP works as a novel E3 ligase in the Pax7-mediated degradation of MyoD in response to skeletal muscle atrophy.

Random-graft polymer-directed synthesis of inorganic mesostructures with ultrathin frameworks.

A widely employed route for synthesizing mesostructured materials is the use of surfactant micelles or amphiphilic block copolymers as structure-directing agents. A versatile synthesis method is described for mesostructured materials composed of ultrathin inorganic frameworks using amorphous linear-chain polymers functionalized with a random distribution of side groups that can participate in inorganic crystallization. Tight binding of the side groups with inorganic species enforces strain in the polymer backbones, limiting the crystallization to the ultrathin micellar scale. This method is demonstrated for a variety of materials, such as hierarchically nanoporous zeolites, their aluminophosphate analogue, TiO2 nanosheets of sub-nanometer thickness, and mesoporous TiO2, SnO2, and ZrO2. This polymer-directed synthesis is expected to widen our accessibility to unexplored mesostructured materials in a simple and mass-producible manner.

Implantable left ventricular assist devices and the kidney.

The use of left ventricular assist devices (LVADs) in treating patients with advanced heart failure restores cardiac output resulting in improved perfusion to multiple organ systems with important clinical benefits. Renal pathophysiology during LVAD support remains an evolving, poorly understood, and potentially dynamic problem. Changes in renal function after LVAD placement have been investigated in multiple studies with contradictory results. Renal dysfunction is common prior to LVAD placement, which complicates postoperative clinical outcomes. The purpose of this review is to assess the latest information regarding the effects of LVADs on renal function with regard to hemodynamics, physiology, pathology and clinical issues prior to and after placement of the devices. The review should then aid in identifying patients best suited to benefit from this technology and to refine the therapy to reduce associated risks.