Functional composites by programming entropy-driven nanosheet growth.

Nanomaterials must be systematically designed to be technologically viable1-5. Driven by optimizing intermolecular interactions, current designs are too rigid to plug in new chemical functionalities and cannot mitigate condition differences during integration6,7. Despite extensive optimization of building blocks and treatments, accessing nanostructures with the required feature sizes and chemistries is difficult. Programming their growth across the nano-to-macro hierarchy also remains challenging, if not impossible8-13. To address these limitations, we should shift to entropy-driven assemblies to gain design flexibility, as seen in high-entropy alloys, and program nanomaterial growth to kinetically match target feature sizes to the mobility of the system during processing14-17. Here, following a micro-then-nano growth sequence in ternary composite blends composed of block-copolymer-based supramolecules, small molecules and nanoparticles, we successfully fabricate high-performance barrier materials composed of more than 200 stacked nanosheets (125 nm sheet thickness) with a defect density less than 0.056 µm-2 and about 98% efficiency in controlling the defect type. Contrary to common perception, polymer-chain entanglements are advantageous to realize long-range order, accelerate the fabrication process (<30 min) and satisfy specific requirements to advance multilayered film technology3,4,18. This study showcases the feasibility, necessity and unlimited opportunities to transform laboratory nanoscience into nanotechnology through systems engineering of self-assembly.

Viscoelastic relaxation and topological fluctuations in glass-forming liquids.

A method for characterizing the topological fluctuations in liquids is proposed. This approach exploits the concept of the weighted gyration tensor of a collection of particles and permits the definition of a local configurational unit (LCU). The first principal axis of the gyration tensor serves as the director of the LCU, which can be tracked and analyzed by molecular dynamics simulations. Analysis of moderately supercooled Kob-Andersen mixtures suggests that orientational relaxation of the LCU closely follows viscoelastic relaxation and exhibits a two-stage behavior. The slow relaxing component of the LCU corresponds to the structural, Maxwellian mechanical relaxation. Additionally, it is found that the mean curvature of the LCUs is approximately zero at the Maxwell relaxation time with the Gaussian curvature being negative. This observation implies that structural relaxation occurs when the configurationally stable and destabilized regions interpenetrate each other in a bicontinuous manner. Finally, the mean and Gaussian curvatures of the LCUs can serve as reduced variables for the shear stress correlation, providing a compelling proof of the close connection between viscoelastic relaxation and topological fluctuations in glass-forming liquids.

SANS characterization of time dependent, slow molecular exchange in an SDS micellar system.

We have investigated the molecular exchange of sodium dodecyl sulfate (SDS) micelles in aqueous solution by time-resolved small angle neutron scattering (TR-SANS) measurements as a function of the surfactant and salt concentration. Starting with deuterated (d-SDS) and protonated (h-SDS) SDS micelles, surfactant exchange across the micelles leads to a randomized distribution of d-SDS and h-SDS within each micelle. By employing the contrast matching technique, we have studied this randomization process which is a direct measure of the molecular exchange of this system. Our results show that the randomization of the pure h-SDS and d-SDS micelles occurs in two steps: first, an almost instantaneous drop in the scattering intensity is observed where ∼80% of the micelles are randomized (contrast matched). After this, micelle randomization progresses slowly spanning over ∼100 hours. Importantly, we show that the kinetics in the second step are dominated by the formation of domains rich in either h-SDS, d-SDS and randomized (50 : 50 h-SDS : d-SDS). The slow exchange step is modeled via a phenomenological approach by drawing analogy to the Langmuir adsorption theory. Finally, the effects of the surfactant and salt concentrations on the instantaneous, and the time dependent randomization of SDS micelles are discussed.

Diffusion characteristics of water molecules in a lamellar structure formed by triblock copolymers.

The distribution and diffusion of water molecules are playing important roles in determining self-assembly and transport properties of polymeric systems. Small-angle neutron scattering (SANS) experiments and molecular dynamics (MD) simulation have been applied to understand the distribution of water molecules and their dynamics in the lamellar membrane formed by Pluronic L62 block copolymers. Penetration of water molecules into the polyethylene oxide (PEO) layers of the membranes has been estimated using scattering length density (SLD) profiles obtained from SANS measurements, which agree well with the molecular distribution observed from MD simulations. The water diffusion coefficient at different regions of the lamellar membrane was further investigated using MD simulation. The diffusion characteristic shows a transition from normal to anomalous diffusion as the position of the water molecule changes from the bulk to PEO and to the polypropylene oxide (PPO) layer. We find that water molecules within the PEO or PPO layers follow subdiffusive dynamics, which can be interpreted by the model of fractional Brownian motion.

Small angle scattering of diblock copolymers profiled by machine learning.

We outline a machine learning strategy for quantitively determining the conformation of AB-type diblock copolymers with excluded volume effects using small angle scattering. Complemented by computer simulations, a correlation matrix connecting conformations of different copolymers according to their scattering features is established on the mathematical framework of a Gaussian process, a multivariate extension of the familiar univariate Gaussian distribution. We show that the relevant conformational characteristics of copolymers can be probabilistically inferred from their coherent scattering cross sections without any restriction imposed by model assumptions. This work not only facilitates the quantitative structural analysis of copolymer solutions but also provides the reliable benchmarking for the related theoretical development of scattering functions.

[Dual-specificity Phosphatase 1 Suppresses Vascular Smooth Muscle Cell Calcification by Optical Atrophy 1-related Pathway].

Objective To investigate the effect of dual-specificity phosphatase 1/optical atrophy 1 (DUSP1/OPA1) signaling pathway on vascular smooth muscle cell (VSMC) calcification.Methods An in vitro model of VSMC calcification was induced by exposure to ß-glycerophosphate and calcium chloride.VSMC calcification was assessed by Alizarin Red S staining and calcium content by ELISA.Apoptosis was detected by TUNEL.Western blotting was employed to determine the protein levels of DUSP1,OPA1,Runt-related transcription factor 2 (Runx-2),bone morphogenetic protein 2 (BMP-2),and cysteinyl aspartate-specific proteinase-3 (Caspase-3).The effects of DUSP1 overexpression and OPA1 knockdown on cell calcification were investigated.Results Calcium chloride and ß-glycerolphosphate induced VSMC calcification and down-regulated the expression levels of DUSP1 (t=11.951,P<0.001) and OPA1 (t=8.487,P<0.001).DUSP1 overexpression promoted OPA1 expression (t=-8.921,P<0.001),attenuated VSMC calcification,reduced calcium content and apoptosis rate,and down-regulated the expression of Runx-2,BMP-2,and active Caspase-3 (all P<0.001).OPA1 knockdown increased calcium content and apoptosis rate,up-regulated the expression of Runx-2,BMP-2,and active Caspase-3,and promoted VSMC calcification (all P<0.001).Conclusion DUSP1 may inhibit the VSMC calcification through the OPA1 signaling pathway.

An exact inversion method for extracting orientation ordering by small-angle scattering.

We outline a nonparametric inversion strategy for determining the orientation distribution function (ODF) of sheared interacting rods using small-angle scattering techniques. With the presence of direct inter-rod interaction and fluid mechanical forces, the scattering spectra are no longer characterized by the azimuthal symmetry in the coordinates defined by the principal directions of simple shear conditions, which severely compounds the reconstruction of ODFs based on currently available methods developed for dilute systems. Using a real spherical harmonic expansion scheme, the real-space ODFs are uniquely determined from the anisotropic scattering spectra and their numerical accuracy is verified computationally. Our method can be generalized to extract ODFs of uniaxially anisotropic objects under different flow conditions in a properly transformed reference frame with suitable basis vectors.

Melatonin attenuates vascular calcification by activating autophagy via an AMPK/mTOR/ULK1 signaling pathway.

Melatonin has been demonstrated to protect against calcification in cyclosporine nephrotoxicity. Autophagy may affect vascular calcification by inhibiting apoptosis and the transdifferentiation process. This study sought to explore whether melatonin attenuates vascular calcification by regulating autophagy via the AMP-activated protein kinase/mammalian target of rapamycin/Unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway. The effects of melatonin on vascular calcification were investigated in vascular smooth muscle cells (VSMCs). Calcium deposits were visualised by Alizarin red staining, while calcium content and alkaline phosphatase (ALP) activity were used to evaluate osteogenic differentiation. Western blots were used to measure expression of runt-related transcription factor 2 (Runx2, an osteogenic transcription factor), light chain 3 (LC3) II/I, and cleaved caspase 3. Melatonin markedly reduced calcium deposition and ALP activity. Runx2 and cleaved caspase 3 were downregulated, whereas LC3 II/I was increased in response to melatonin, and was accompanied by decreased apoptosis. An immunofluorescence assay revealed that melatonin treatment markedly decreased Runx2 expression and upregulated LC3 expression. Treatment with the autophagy inhibitor 3-methyladenine reversed this phenomenon. Melatonin significantly increased expression of p-AMPK and p-ULK1, and decreased mTOR expression. Treatment with compound C (an inhibitor of AMPK) or MHY1485 (an agonist of mTOR) ablated the observed benefits of melatonin treatment. Melatonin protects VSMCs against calcification by activating autophagy via the AMPK/mTOR/ULK1 pathway.

Melatonin attenuates vascular calcification by inhibiting mitochondria fission via an AMPK/Drp1 signalling pathway.

Mitochondrial fission plays a role in cardiovascular calcification. Melatonin has previously been shown to protect against cardiovascular disease, so this study sought to explore whether it attenuates vascular calcification by regulating mitochondrial fission via the AMP-activated protein kinase/dynamin-related protein 1 (AMPK/Drp1) signalling pathway. The effects of melatonin on vascular calcification were investigated in vascular smooth muscle cells (VSMCs). Calcium deposits were visualized by Alizarin red staining, while calcium content and alkaline phosphatase (ALP) activity were used to evaluate osteogenic differentiation. Western blots were used to measure the expression of runt-related transcription factor 2 (Runx2), Drp1 and cleaved caspase 3. Melatonin markedly reduced calcium deposition and ALP activity. Runx2 and cleaved caspase 3 were down-regulated, Drp1 was reduced in response to melatonin, and this was accompanied by decreased apoptosis. Melatonin also reduced levels of mitochondrial superoxide, reversed ß-glycerophosphate (ß-GP)-induced ΔΨm dissipation and decreased mitochondrial fragmentation. The effects of melatonin in ß-GP-treated VSMCs were similar to those of mitochondrial division inhibitor 1. Melatonin significantly activated the expression of AMPK and decreased Drp1 expression. Treatment with compound C ablated the observed benefits of melatonin treatment. These findings indicate that melatonin protects VSMCs against calcification by inhibiting mitochondrial fission via the AMPK/Drp1 pathway.

Complexation of Pluronic L62 (EO6)-(PO34)-(EO6)/aerosol-OT (sodium bis(2-ethylhexyl)sulfosuccinate) in aqueous solutions investigated by small angle neutron scattering.

We investigate the phase behaviours of Pluronic L62 in aqueous solution in the presence of aerosol-OT (AOT) molecules by small angle neutron scattering (SANS). The presence of AOT significantly changes the micellization phenomenon of L62 micelles in aqueous solution, including their critical micelle temperature (CMT), global size, and asphericity. The origin of these observations is attributed to the complexation between the neutral L62 surfactants and the ionic AOT molecules, which additionally provides charge to the mixed micelles: we analyse the data and extract meaningful information using the Ornstein-Zernike integral formalism. As a result, we observe that the co-micellization of L62 and AOT is very stable across a wide temperature range.

Determining population densities in bimodal micellar solutions using contrast-variation small angle neutron scattering.

Self-assembly of amphiphilic polymers in water is of fundamental and practical importance. Significant amounts of free unimers and associated micellar aggregates often coexist over a wide range of phase regions. The thermodynamic and kinetic properties of the microphase separation are closely related to the relative population density of unimers and micelles. Although the scattering technique has been employed to identify the structure of micellar aggregates as well as their time-evolution, the determination of the population ratio of micelles to unimers remains a challenging problem due to their difference in scattering power. Here, using small-angle neutron scattering (SANS), we present a comprehensive structural study of amphiphilic n-dodecyl-PNIPAm polymers, which shows a bimodal size distribution in water. By adjusting the deuterium/hydrogen ratio of water, the intra-micellar polymer and water distributions are obtained from the SANS spectra. The micellar size and number density are further determined, and the population densities of micelles and unimers are calculated to quantitatively address the degree of micellization at different temperatures. Our method can be used to provide an in-depth insight into the solution properties of microphase separation, which are present in many amphiphilic systems.

Magnetic Micro Sensors with Two Magnetic Field Effect Transistors Fabricated Using the Commercial Complementary Metal Oxide Semiconductor Process.

The fabrication and characterization of a magnetic micro sensor (MMS) with two magnetic field effect transistors (MAGFETs) based on the commercial complementary metal oxide semiconductor (CMOS) process are investigated. The magnetic micro sensor is a three-axis sensing type. The structure of the magnetic microsensor is composed of an x/y-MAGFET and a z-MAGFET. The x/y-MAGFET is employed to sense the magnetic field (MF) in the x- and y-axis, and the z-MAGFET is used to detect the MF in the z-axis. To increase the sensitivity of the magnetic microsensor, gates are introduced into the two MAGFETs. The sensing current of the MAGFET enhances when a bias voltage is applied to the gates. The finite element method software Sentaurus TCAD was used to analyze the MMS's performance. Experiments show that the MMS has a sensitivity of 182 mV/T in the x-axis MF and a sensitivity of 180 mV/T in the y-axis MF. The sensitivity of the MMS is 27.8 mV/T in the z-axis MF.

Structural properties of the evolution of CTAB/NaSal micelles investigated by SANS and rheometry.

Surfactants are amphiphilic molecules that spontaneously self-assemble in aqueous solution into various ordered and disordered phases. Under certain conditions, one-dimensional structures in the form of long, flexible wormlike micelles can develop. Cetyltrimethylammonium bromide (CTAB) is one of the most widely studied surfactants, and in the presence of sodium salicylate (NaSal), wormlike micelles can form at very dilute concentrations of surfactant. We carry out a systematic study of the structures of CTAB/NaSal over a surfactant concentration range of 2.5-15 mM and at salt-to-surfactant molar ratios of 0.5-10. Using small-angle neutron scattering (SANS), we qualitatively and quantitatively characterize the equilibrium structures of CTAB/NaSal, mapping the phase behavior of CTAB/NaSal at low concentrations within the region of phase space where nascent wormlike micelles transition into long and entangled structures. Complementary rheological assessments not only demonstrate the significant influence of the inter-micellar Coulombic interaction on the micellar structure but also suggest the potential existence of a hierarchical structure which is beyond the accessibility of the SANS technique.

Influence of side chain isomerism on the rigidity of poly(3-alkylthiophenes) in solutions revealed by neutron scattering.

Using small-angle neutron scattering, we conducted a detailed conformational study of poly(3-alkylthiophene) solutions in deuterated dichlorobenzene. The focus was placed on addressing the influence of the spatial arrangement of side chain constituents on backbone conformation. We demonstrate that by introducing a branch point in the side chain, side chain steric interactions may promote torsional motion between backbone units, resulting in greater chain flexibility. Our findings highlight the key role of topological isomerism in determining the chain rigidity and throw new light on the debate about the effective approaches for optimizing the electronic properties of conducting polymers via side chain engineering.

Melatonin Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Autophagy Via an AMPK/mTOR Signaling Pathway.

BACKGROUND/AIMS: Melatonin has been demonstrated to protect cardiac microvascular endothelial cells (CMECs) against ischemia/reperfusion injury (IRI). Autophagy plays different roles in the heart during ischemia and reperfusion. The AMP activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway is associated with autophagy. This study sought to explore whether melatonin regulates CMEC autophagy through the AMPK/mTOR signaling pathway. METHODS: The effects of melatonin in IRI were investigated in vivo rat models and in vitro neonatal CMECs. Myocardial infarct size was achieved by Evans blue and triphenyltetrazolium chloride staining. The severity of cell injury was evaluated by cell vitality and lactate dehydrogenase (LDH) release assays, and autophagy was evaluated by transmission electron microscopy and the assessment of autophagy-related gene expression, such as that of Beclin 1 and light chain 3-II. RESULTS: In vivo, melatonin markedly reduced infarcted area, improved cardiac function and decreased LDH release. However, the AMPK activator AICAR and the mTOR inhibitor rapamycin reduced the protective effects of melatonin on IRI. In vitro, Beclin1 and light chain 3-II protein were found to be down-regulated and autophagosomes were found to be reduced in response to melatonin, together with an increase in cell vitality and a decrease in LDH. Treatment with AICAR or rapamycin ablated the benefit observed with melatonin treatment. CONCLUSIONS: Melatonin played an important and protective role in CMECs by inhibiting autophagy against IRI via the AMPK/mTOR system.

Scaling Behavior of Anisotropy Relaxation in Deformed Polymers.

Drawing an analogy to the paradigm of quasielastic neutron scattering, we present a general approach for quantitatively investigating the spatiotemporal dependence of structural anisotropy relaxation in deformed polymers by using small-angle neutron scattering. Experiments and nonequilibrium molecular dynamics simulations on polymer melts over a wide range of molecular weights reveal that their conformational relaxation at relatively high momentum transfer Q and short time can be described by a simple scaling law, with the relaxation rate proportional to Q. This peculiar scaling behavior, which cannot be derived from the classical Rouse and tube models, is indicative of a surprisingly weak direct influence of entanglement on the microscopic mechanism of single-chain anisotropy relaxation.

Local elasticity in nonlinear rheology of interacting colloidal glasses revealed by neutron scattering and rheometry.

The flow of colloidal suspensions is ubiquitous in nature and industry. Colloidal suspensions exhibit a wide range of rheological behavior, which should be closely related to the microscopic structure of the systems. With in situ small-angle neutron scattering complemented by rheological measurements, we investigated the deformation behavior of a charge-stabilized colloidal glass at particle level undergoing steady shear. A short-lived, localized elastic response at particle level, termed as the transient elasticity zone (TEZ), was identified from the neutron spectra. The existence of the TEZ, which could be promoted by the electrostatic interparticle potential, is a signature of deformation heterogeneity: the body of fluids under shear behaves like an elastic solid within the spatial range of the TEZ but like fluid outside the TEZ. The size of the TEZ shrinks as the shear rate increases in the shear thinning region, which shows that the shear thinning is accompanied by a diminishing deformation heterogeneity. More interestingly, the TEZ is found to be the structural unit that provides the resistance to the imposed shear, as evidenced by the quantitative agreement between the local elastic stress sustained by the TEZ and the macroscopic stress from rheological measurements at low and moderate shear rates. Our findings provide an understanding on the nonlinear rheology of interacting colloidal glasses from a micro-mechanical view.

Prognostic value of plasma DPP4 activity in ST-elevation myocardial infarction.

BACKGROUND: Dipeptidyl peptidase-4 (DPP4) regulates blood glucose levels and inflammation, and it is also implicated in the pathophysiological process of myocardial infarction (MI). Plasma DPP4 activity (DPP4a) may provide prognostic information regarding outcomes for ST-segment elevation MI (STEMI) patients. METHODS: Blood samples were obtained from 625 consecutively admitted, percutaneous coronary intervention-treated STEMI patients with a mean age of 57 years old. DPP4a was quantified using enzymatic assays. RESULTS: The median follow-up period was 30 months. Multivariate Cox-regression analyses (adjusted for confounding variables) showed that a 1 U/L increase of DPP4a did not associate with risks of major adverse cardiac or cerebrovascular events (MACCE), cardiovascular mortality, MI, heart failure readmission, stroke, non-cardiovascular mortality and repeated revascularization. However, in a subset of 149 diabetic STEMI patients, DPP4a associated with an increased risk of MACCE (HR 1.16; 95% CI 1.04-1.30; p = 0.01). CONCLUSIONS: DPP4a did not associate with cardiovascular events and non-cardiovascular mortality in non-diabetic STEMI patients. However, DPP4a may be associated with future MACCE in diabetic STEMI patients. Trial registration NCT03046576, registered on 5 February, 2017, retrospectively registered.

Effects of liraglutide on left ventricular function in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: Several studies have shown that exenatide protects against ischemia-reperfusion injury and improves cardiac function in patients with acute ST-segment elevation myocardial infarction (STEMI). The effects of liraglutide, a glucagon-like peptide-1 analogue, on STEMI patients remain unclear. We planned to evaluate the effects of liraglutide on left ventricular function after primary percutaneous coronary intervention for STEMI. METHODS: A total of 92 patients were randomized 1:1 to receive either liraglutide or placebo for 7 days. Study treatment was commenced 30 minutes before intervention (1.8 mg) and maintained for 7 days after the procedure (0.6 mg for 2 days, 1.2 mg for 2 days, followed by 1.8 mg for 3 days). Eighty-five patients completed the trial. Transthoracic echocardiography was used to assess left ventricular function. RESULTS: At 3 months, the primary end point, a difference in change of left ventricular ejection fraction between the two groups was +4.1% (95% CI +1.1% to +6.9%) (P < .001). There was a tendency for a lower rate of no-reflow in liraglutide group that did not reach statistical significance (7% vs control group 15%, P = .20). Liraglutide could significantly improve stress hyperglycemia (P < .05). In addition, liraglutide elicited favorable changes in markers of inflammation and endothelial function. CONCLUSION: A short 7-day course of liraglutide in STEMI patients treated with primary percutaneous coronary intervention is associated with mild improvement in left ventricular ejection fraction at 3 months.

Classification of Benign and Malignant Breast Tumors in Ultrasound Images with Posterior Acoustic Shadowing Using Half-Contour Features.

Posterior acoustic shadowing (PAS) can bias breast tumor segmentation and classification in ultrasound images. In this paper, half-contour features are proposed to classify benign and malignant breast tumors with PAS, considering the fact that the upper half of the tumor contour is less affected by PAS. Adaptive thresholding and disk expansion are employed to detect tumor contours. Based on the detected full contour, the upper half contour is extracted. For breast tumor classification, six quantitative feature parameters are analyzed for both full contours and half contours, including standard deviation of degree (SDD), which is proposed to describe tumor irregularity. Fifty clinical cases (40 with PAS and 10 without PAS) were used. Tumor circularity (TC) and SDD were both effective full- and half-contour parameters in classifying images without PAS. Half-contour TC [74 % accuracy, 72 % sensitivity, 76 % specificity, 0.78 area under the receiver operating characteristic curve (AUC), p > 0.05] significantly improved the classification of breast tumors with PAS compared to that with full-contour TC (54 % accuracy, 56 % sensitivity, 52 % specificity, 0.52 AUC, p > 0.05). Half-contour SDD (72 % accuracy, 76 % sensitivity, 68 % specificity, 0.81 AUC, p < 0.05) improved the classification of breast tumors with PAS compared to that with full-contour SDD (62 % accuracy, 80 % sensitivity, 44 % specificity, 0.61 AUC, p > 0.05). The proposed half-contour TC and SDD may be useful in classifying benign and malignant breast tumors in ultrasound images affected by PAS.