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Selective induction of tumor thrombus infarction is a promising antitumor strategy. Non-persistent embolism due to non-compacted thrombus and activated fibrinolytic system within the tumor large blood vessels and tumor margin recurrence are the main therapeutic bottlenecks. Herein, an erythrocyte membrane-coated invisible acoustic-sensitive nanoparticle (TXA+DOX/PFH/RBCM@cRGD) is described, which can induce tumor thrombus infarction by precisely damaging tumor vascular endothelium. It is revealed that TXA+DOX/PFH/RBCM@cRGD can effectively accumulate on the endothelial surface of tumor vessels with the help of the red blood cell membrane (RBCM) stealth coating and RGD cyclic peptide (cRGD), which can be delivered in a targeted manner as nanoparticle missiles. As a kind of phase-change material, perfluorohexane (PFH) nanodroplets possess excellent acoustic responsiveness. Acoustic-sensitive missiles can undergo an acoustic phase transition and intense cavitation with response to low-intensity focused ultrasound (LIFU), damaging the tumor vascular endothelium, rapidly initiating the coagulation cascade, and forming thromboembolism in the tumor vessels. The drugs loaded in the inner water phase are released explosively. Tranexamic acid (TXA) inhibits the fibrinolytic system, and doxorubicin (DOX) eliminates the margin survival. In summary, a stealthy and acoustically responsive multifunctional nanoparticle delivery platform is successfully developed for inducing thrombus infarction by precisely damaging tumor vascular endothelium.

This paper is concerned with a semi-linear elliptic problem with Robin boundary condition: \begin{document}$ \begin{equation} \left\{\begin{array}{lll} \varepsilon \Delta w-\lambda w^{1+\chi} = 0, &\text{in} \ \Omega\\ \nabla w \cdot \vec{n}+\gamma w = 0, & \text{on} \ \partial \Omega \end{array}\right. \end{equation} ~~~~~~~~~~~~~~~~~~~~(*)$\end{document} where \begin{document}$ \Omega \subset {\mathbb R}^N (N\geq 1) $\end{document} is a bounded domain with smooth boundary, \begin{document}$ \vec{n} $\end{document} denotes the unit outward normal vector of \begin{document}$ \partial \Omega $\end{document} and \begin{document}$ \gamma \in {\mathbb R}/\{0\} $\end{document} . \begin{document}$ \varepsilon $\end{document} and \begin{document}$ \lambda $\end{document} are positive constants. The problem (*) is derived from the well-known singular Keller-Segel system. When \begin{document}$ \gamma>0 $\end{document} , we show there is only trivial solution \begin{document}$ w = 0 $\end{document} . When \begin{document}$ \gamma and \begin{document}$ \Omega = B_R(0) $\end{document} is a ball, we show that problem (*) has a non-constant solution which converges to zero uniformly as \begin{document}$ \varepsilon $\end{document} tends to zero. The main idea of this paper is to transform the Robin problem (*) to a nonlocal Dirichelt problem by a Cole-Hopf type transformation and then use the shooting method to obtain the existence of the transformed nonlocal Dirichlet problem. With the results for (*), we get the existence of non-constant stationary solutions to the original singular Keller-Segel system.

Metal-organic framework (MOF) membranes have enormous potential in separation applications. There are several MOF membranes grown on polymer substrates aimed for scale-up, but their brittleness hampers any industrial application. Herein, intergrown continuous polypropylene (PP)-supported ZIF-8 membranes have been successfully synthesized via fast current-driven synthesis (FCDS) within 1 h. The PP-supported ZIF-8 membranes exhibit a promising separation factor of 122 ± 13 for binary C3H6-C3H8 mixtures combined with excellent flexibility behavior. The C3H6/C3H8 separation performance of the PP-supported ZIF-8 membrane was found to be constant after bending the supported ZIF-8 film with a curvature of 92 m-1. This outstanding mechanical property is crucial for practical applications. Moreover, we further synthesized ZIF-8 membranes on various polymer substrates and even polymer hollow fibers to demonstrate the production scalability.

Though the boundary layer formation in the chemotactic process has been observed in experiment (cf. [63] ), the mathematical study on the boundary layer solutions of chemotaxis models is just in its infant stage. Apart from the sophisticated theoretical tools involved in the analysis, how to impose/derive physical boundary conditions is a state-of-the-art in studying the boundary layer problem of chemotaxis models. This paper will proceed with a previous work [24] in one dimension to establish the convergence of boundary layer solutions of the Keller–Segel model with singular sensitivity in a two-dimensional space (half-plane) with respect to the chemical diffusion rate denoted by e ≥ 0 . Compared to the one-dimensional boundary layer problem, there are many new issues arising from multi-dimensions such as possible Prandtl type degeneracy, curl-free preservation and well-posedness of large-data solutions. In this paper, we shall derive appropriate physical boundary conditions and gradually overcome these barriers and hence establish the convergence of boundary layer solutions of the singular Keller–Segel system in the half-plane as the chemical diffusion rate vanishes. Specially speaking, we justify that the boundary layer converges to the outer layer (solution with e = 0 ) plus the inner layer as e → 0 , where both outer and inner layer profiles are precisely derived and well understood. By doing this, the structure of boundary layer solutions is clearly characterized. We hope that our results and methods can shed lights on the understanding of underlying mechanisms of the boundary layer patterns observed in the experiment for chemotaxis such as the work by Tuval et al. [63] , and open a new window in the future theoretical study of chemotaxis models.

A novel ratio electrochemical biosensor based on multi-functional nanocomposite was developed. Fe

NOV1 is a stilbene cleavage oxygenase (SCO) responsible for the oxidative cleavage of the central double bond of stilbenes, forming two phenolic aldehydes. In the active site of NOV1, the iron cofactor is coordinated by four histidines and no negatively charged ligand, which is unusual for iron-containing enzymes. Here, on the basis of the recently obtained crystal structure of NOV1, we performed quantum mechanics/molecular mechanics (QM/MM) calculations to elucidate the reaction mechanism of NOV1. According to our calculations, two binding modes of O2 to Fe(II) (end-on and side-on modes) have been recognized, and the end-on mode is suitable for catalysis. The side-on mode, which has been obtained from the crystal, is an inactive form, which should first change to the end-on mode to initiate the catalytic reaction. For the reactant in end-on mode, the triplet and quintet states correspond to very similar energies. Of the three considered pathways, two pathways (path_a and path_b1, which differ only in the order of the first C–O bond formation) involving the dioxetane intermediate are calculated to be favorable, which can confirm the dioxygenase mechanism of NOV1. However, the pathway (path_b2) involving the epoxide intermediate corresponds to high energy barriers for the formation of the second C–O bond (27.49 and 31.56 kcal mol−1 on the triplet and quintet state surfaces) and can be ruled out. However, in path_b2, the formation of the epoxide intermediate is easy, which may react with the solvent water (non-enzymatic reaction) to form the by-product. In addition, the different protonation states of 4′-OH of the substrate and K134, as well as the coordination of additional water molecules with the iron, do not influence the reaction barrier.

ZIF-8 membrane has the potential for CO2 /CH4 separation based on size exclusion. But if traditionally prepared by solvothermal methods, it shows only negligible selectivity due to the linker mobility. Here, ≈500 nm-thin hybrid ZIF-7x -8 membranes with suppressed linker mobility and narrowed window aperture are prepared by a fast current-driven synthesis (FCDS) within 20 min. The in situ electric field during FCDS allows the formation of stiffened ZIF-8_Cm as parent skeleton and the mixed-linker strategy is applied to narrow the aperture size simultaneously. The ZIF-722 -8 membrane shows significantly sharpened molecular sieving for CO2 /CH4 with a separation factor above 25, which soared tenfold compared with other unmodified ZIF-8 membranes. Additionally, the membrane shows exceptional separation performance for H2 /CH4 and CO2 /N2 , with separation factors of 71 and 20, respectively. After 180 h temperature swing operation, it still maintains the excellent separation performance.

Continental flow plays a significant role in the global ecosystem. With increased global warming and a booming economy exacerbating water scarcity, global analyses of continental discharge are of great relevance to water management. In this paper, the Mann-Kendall (MK) test, with variations accounting for lag-1 autocorrelation, full autocorrelation, and long-term persistence, was used to detect the long-term flow trends in 916 of the world’s largest ocean-reaching rivers over the period 1948–2004. Field significance was evaluated using Walker’s test. Globally, the results revealed more decreases in streamflow than increases. With the traditional MK test, 503 rivers had decreased streamflow, with 120 showing significant decreases, whereas 408 rivers had increased streamflow, with 51 showing significant increases. Regionally, positive streamflow trends mainly occurred in high-latitude areas and negative streamflow trends mainly occurred in low-latitude areas, a pattern that can be attributed to uneven precipitation and the effects of global warming. When the full autocorrelation structure and long-term persistence behavior were taken into account in the trend analysis, there was a large reduction in the number of rivers with significant changes in streamflow. Negligible departures from the traditional MK results were observed when only the lag-1 autocorrelation was taken into consideration. For the Americas and Europe, annual integrated river flow showed a slight upward trend; for other continents, there was a slight downward trend. For all oceans except the Arctic Ocean, integrated river flow had a downward trend. We investigated the causal relationships between streamflow and ocean signals using the Granger causality test. El Nino–Southern Oscillation (ENSO) signals were significantly causal for river flow in over 36% of global rivers tested. The influence of the Arctic Oscillation (AO) and the North Atlantic Oscillation (NAO) was significant in more than a quarter of rivers studied. The Pacific Decadal Oscillation (PDO) was responsible for the variation in streamflow for over a quarter of rivers studied. Streamflow was affected by the interactions between ocean signals as well as by anthropogenic activities.

This paper is concerned with the stability of boundary layer solutions for a viscous hyperbolic system transformed via a Cole--Hopf transformation from a singular chemotactic system modeling the in...

This paper is concerned with the boundary layer problem for a hyperbolic system transformed via a Cole–Hopf type transformation from a repulsive chemotaxis model with logarithmic sensitivity proposed in [23] , [34] modeling the biological movement of reinforced random walkers which deposit a non-diffusible (or slowly moving) signal that modifies the local environment for succeeding passages. By prescribing the Dirichlet boundary conditions to the transformed hyperbolic system in an interval ( 0 , 1 ) , we show that the system has the boundary layer solutions as the chemical diffusion coefficient e → 0 , and further use the formal asymptotic analysis to show that the boundary layer thickness is e 1 / 2 . Our work justifies the boundary layer phenomenon that was numerically found in the recent work [25] . However we find that the original chemotaxis system does not possess boundary layer solutions when the results are reverted to the pre-transformed system.

Serum paraoxonase 1 (PON1) is a calcium-dependent enzyme that can catalyze the hydrolysis of multiple substrates, including lactones, thiolactones, carbonates, esters and phosphotriesters, as well as the formation of a variety of lactones. To better understand the lactonase mechanism of PON1, the hydrolysis of dihydrocoumarin, which is considered as a native substrate of PON1, has been investigated by using a combined quantum mechanics and molecular mechanics (QM/MM) approach. Two possible reaction pathways with either Glu53 or His115 acts as the general base have been considered. On the basis of our calculations, these two pathways correspond to the overall energy barriers of 12.5 and 9.0 kcal mol−1, respectively. During the catalytic reaction, if one of the two residues (Glu53 and His115) acts as the catalytic base, the other one forms strong hydrogen bonding interaction with the attacking hydroxide to facilitate the hydrolysis. However, mutation studies reveal that Glu53 is necessary for hydrolysis, whereas His115 is not essential but can promote the activity of PON1. Natural population analysis indicates that the catalytic Ca2+ does not act as Lewis acid but plays structural role in fixing the orientations of the substrate and related residues. In addition, Asp269 is found to coordinate with Ca2+ cation and facilitate the protonation of the alkoxide leaving group by forming hydrogen bond with lactone. These results can explain the fact that mutation of Glu53 results in the loss of activity of PON1, and the hydrolysis of dihydrocoumarin is unaffected by mutation of H115.

Buprofezin is a commonly used chemical with satisfactory biological activity against sucking insect pests, but its disposal can cause serious environmental problems. To study the feasibility of remedying contamination by buprofezin, microcosm experiments were carried out to study the effects of various concentrations of buprofezin and Sphingobium sp. LY-6 on soil bacterial communities in soils collected from vegetable fields. In this experiment, the results showed that buprofezin was effectively degraded by Sphingobium sp. LY-6 in incubation soils. Comparing to non-incubated soils, the cumulative degradation ratio of buprofezin was significantly increased, up to the extent of 85 and 51%, in the initial concentration of 10 and 100 mg kg(-1). The abundance and community structure of the bacterial communities were analysed by real-time PCR (qPCR) and terminal-restriction fragment length polymorphism (T-RFLP). The findings suggest that buprofezin had a negative effect on soil bacterial community, and decreases in bacterial abundance were observed in the later part of the incubation period. The bacterial community structure and diversity shifted significantly at each sampling time. In conclusion, the buprofezin-degrading strain LY-6 played a major role in the bioremediation of the buprofezin-contaminated soil and influenced the dynamics and structure of the bacterial community, demonstrating the great potential of exogenous microorganisms for soil remediation.

The Taxus canadensis phenylalanine aminomutase (TcPAM) catalyze the isomerization of (S)-alpha-phenylalanine to the (R)-beta-isomer. The active site of TcPAM contains the signature 5-methylene-3,5-dihydroimidazol-4-one (MIO) prosthesis, observed in the ammonia lyase class of enzymes. Up to now, there are two plausible mechanisms for these MIO-dependent enzymes, i.e., the amino-MIO adduct mechanism and the Friedel-Crafts-type reaction mechanism. In response to this mechanistic uncertainty, the phenylalanine aminomutase mechanism was investigated by using density functional methods. The calculation results indicate that: (1) the reaction prefers the amino-MIO adduct mechanism where the 2,3-amine shift process contains six elementary steps; (2) the ammonia elimination step proceeds through an E2 mechanism; (3) a single C1-C alpha bond rotation of 180 degrees in the cinnamate skeleton occurs in the active site prior to the rebinding of NH2 group to the cinnamate. This can be used to explain the stereochemistry of the TcPAM reaction product which is contrary to those of the PaPAM and SgTAM enzymes. Based on these calculations, the roles of important residues in the active site were also elucidated. (C) 2013 Elsevier Inc. All rights reserved.

A new promising phosphor material established on Eu3+ doped monoclinic (SrAl2Si2O8)/tetragonal (Sr2Al2SiO7) composite with controllable photoluminescence (PL) has been successfully synthesized using one-pot processing technology. Completely phase-separated SrAl2Si2O8/Sr2Al2SiO7 can be achieved in a single matrix starting from single-source precursors. In this work, a series of composite phosphor samples (including 50 mol%(SrAl2Si2O8)–50 mol%(Sr2Al2SiO7): 2, 6, 10, and 14 mol% Eu) were obtained after thermal treatment at 1300 °C for 36 h. The SrAl2Si2O8/Sr2Al2SiO7:Eu composites yield red (c. 616 nm) and blue (c. 440 nm) emission light when excited by near-UV 380 nm light. The crystal structures were investigated by X-ray diffraction after phase separation, and showed relatively small changes in lattice parameters. X-ray photoelectron spectroscopy and electron paramagnetic resonance for the composites showed red and blue emissions originating from Eu3+ and Eu2+ ions, which served as two different but coexisting activators due to the different crystal structural characteristics in Sr2Al2SiO7 and SrAl2Si2O8, respectively. The energy transfer between Eu3+ and Eu2+ in the same matrix tends to cause the alternating changes in the relative intensity of red and blue emitting lights with varied Eu concentration. As a result, controllable luminescence over the whole visible region can be obtained by doping appropriate rare earth contents or tailoring initial compositions of the precursors.

Epinephrine is a naturally occurring adrenomedullary hormone that transduces environmental stressors into cardiovascular actions. As the only route in the catecholamine biosynthetic pathway, Phenylethanolamine N-methyltransferase (PNMT) catalyzes the synthesis of epinephrine. To elucidate the detailed mechanism of enzymatic catalysis of PNMT, combined quantum-mechanical/molecular-mechanical (QM/MM) calculations were performed. The calculation results reveal that this catalysis contains three elementary steps: the deprotonation of protonated norepinphrine, the methyl transferring step and deprotonation of the methylated norepinphrine. The methyl transferring step was proved to be the rate-determining step undergoing a SN2 mechanism with an energy barrier of 16.4 kcal/mol. During the whole catalysis, two glutamic acids Glu185 and Glu219 were proved to be loaded with different effects according to the calculations results of the mutants. These calculation results can be used to explain the experimental observations and make a good complementarity for the previous QM study. (C) 2012 Elsevier B.V. All rights reserved.

The quantum-mechanical/molecular-mechanical (QM/MM) method was used to study the glycosylation mechanism of rice BGlu1 β-glucosidase in complex with laminaribiose. The calculation results reveal that the glycosylation step experiences a concerted process from the reactant to the glycosyl-enzyme complex with an activation barrier of 15.7 kcal/mol, in which an oxocarbenium cation-like transition state (TS) is formed. At the TS, the terminal saccharide residue planarizes toward the half-chair conformation, and the glycosidic bond cleavage is promoted by the attacks of proton donor (E176) on glycosidic oxygen and nucleophilic residue (E386) on the anomeric carbon of laminaribiose. Both the nucleophilic glutamate (E386) and acid/base catalyst (E176) establish shorter hydrogen bridges with the C₂-hydroxyl groups of sugar ring, which play an important role in the catalytic reaction of rice BGlu1 β-glucosidase.

Recent theoretical studies on N-heterocyclic carbenes catalyzed Staudinger reactions revealed that the stereoselectivities are determined by an elementary reaction step, that is, the reaction of an imine with N-heterocyclic carbene-ketene zwitterionic intermediate ( INT N-k ). To better understand the stereoselectivities of some of the experimentally reported reaction systems, the corresponding transition states were studied further by using an ONIOM approach. A combination of B3LYP/6-31G(d) and PM3 levels of theory was used for transition state optimization, and M06-2X/6-31+G(d,p) level for single point calculations. The calculations were found to provide predictions that were in qualitative agreement with the sense and magnitude of experimental stereoselectivities. By analyzing the electronic structures of the transition states, the origin of divergent stereoselectivities in different N-heterocyclic carbenes catalyzed system can be attributed to the cooperation of the electrostatic and steric effects involved in the reaction of imines with N-heterocyclic carbene-ketene intermediates. These results may provide useful information for selecting the N-heterocyclic carbene catalysts in the synthesis of β-lactams.

Archaeal fructose-1,6-bisphosphate aldolase/phosphatase (FBPA/P) is a newly identified unusual bifunctional enzyme (Nature, 2010, 464, 1077), which contains one single catalytic domain but catalyzes two chemically distinct reactions of gluconeogenesis. It is different from the ordinary enzymes whose active sites are responsible for a specific reaction. To explore the catalytic characteristic of FBPA/P, the aldol condensation mechanism of bifunctional FBPA/P has been investigated using quantum mechanics/molecular mechanics (QM/MM) method. The whole reaction process can be divided into two half-reactions involving seven elementary steps. A Schiff base intermediate is theoretically confirmed, agreeing well with the recently resolved crystal structures (Nature, 2011, 478, 538). The free energy barrier of the rate-limiting step is calculated to be 22.2 kcal mol(-1), which is a concerted process of a nucleophilic attack by the enolic carbon to the ketonic carbon and a proton transfer from Tyr229 to the ketonic oxygen. Lys232 plays an important role in forming a Schiff base intermediate with the substrate (DHAP). Tyr229 functions as a proton shuttle during the catalysis. This is the first theoretical study on the aldol condensation mechanism of FBPA/P, which may provide useful information for understanding bifunctional enzymes.