AaTs-1: A Tetrapeptide from Androctonus australis Scorpion Venom,Inhibiting U87 Glioblastoma Cells Proliferation by p53 and FPRL-1 Up-Regulations

Glioblastoma is an aggressive cancer, against which medical professionals are still quite helpless, due to its resistance to current treatments. Scorpion toxins have been proposed as a promising alternative for the development of effective targeted glioblastoma therapy and diagnostic. However, the exploitation of the long peptides could present disadvantages. In this work, we identified and synthetized AaTs-1, the first tetrapeptide from Androctonus australis scorpion venom (Aa), which exhibited an antiproliferative effect specifically against human glioblastoma cells. Both the native and synthetic AaTs-1 were endowed with the same inhibiting effect on the proliferation of U87 cells with an IC₅₀ of 0.56 mM. Interestingly, AaTs-1 was about two times more active than the anti-glioblastoma conventional chemotherapeutic drug, temozolomide (TMZ), and enhanced its efficacy on U87 cells. AaTs-1 showed a significant similarity with the synthetic peptide WKYMVm, an agonist of a G-coupled formyl-peptide receptor, FPRL-1, known to be involved in the proliferation of glioma cells. Interestingly, the tetrapeptide triggered the dephosphorylation of ERK, p38, and JNK kinases. It also enhanced the expression of p53 and FPRL-1, likely leading to the inhibition of the store operated calcium entry. Overall, our work uncovered AaTs-1 as a first natural potential FPRL-1 antagonist, which could be proposed as a promising target to develop new generation of innovative molecules used alone or in combination with TMZ to improve glioblastoma treatment response. Its chemical synthesis in non-limiting quantity represents a valuable advantage to design and develop low-cost active analogues to treat glioblastoma cancer.     

Numerical and experimental studies of molten pool formation during an interaction of a pulse laser (Nd:YAG) with a magnesium alloy

A pulse laser (Nd:YAG) interaction with an AZ91 magnesium alloy has been experimentally and numerically studied. A two-dimensional (2D) axisymmetric model of a molten pool created by a laser heat source has been developed. The elaborated model solves the coupled equations of a laminar fluid flow and heat transfer to demonstrate the flow behavior in the pool. This model takes into account the coupled effects of buoyancy and Marangoni forces, the thermophysic variation properties with temperature, and the radiation and convection heat losses. Concerning numerical results, the molten temperature distribution, velocity field and molten shape were discussed. It was noted that the Marangoni flow significantly alters the characteristics of the thawing and solidifying processes, and makes the molten pool wider and shallower. On the other hand, the experimental results showed that the material thermal properties have significant effects on the transport phenomena which takes place in the molten pool, and consequently on the formation as well as the shape of the pool. Finally, a comparison between the numerical and experimental results exhibited a good agreement.     

Semistability of switched dynamical systems,Part I: Linear system theory

This paper develops semistability and uniform semistability analysis results for switched linear systems. Semistability is the property whereby the solutions of a dynamical system converge to Lyapunov stable equilibrium points determined by the system’s initial conditions. Since solutions to switched systems are a function of the system’s initial conditions as well as the switching signals, uniformity here refers to the convergence rate of the multiple solutions as the switching signal evolves over a given switching set. The main results of the paper involve sufficient conditions for semistability and uniform semistability using multiple Lyapunov functions and sufficient regularity assumptions on the class of switching signals considered.     

Magnetic nanocarriers of doxorubicin coated with poly(ethylene glycol) and folic acid: relation between coating structure, surface properties, colloidal stability, and cancer cell targeting

We report the efficient one-step synthesis and detailed physicochemical evaluation of novel biocompatible nanosystems useful for cancer therapeutics and diagnostics (theranostics). These systems are the superparamagnetic iron oxide nanoparticles (SPIONs) carrying the anticancer drug doxorubicin and coated with the covalently bonded biocompatible polymer poly(ethylene glycol) (PEG), native and modified with the biological cancer targeting ligand folic acid (PEG-FA). These multifunctional nanoparticles (SPION-DOX-PEG-FA) are designed to rationally combine multilevel mechanisms of cancer cell targeting (magnetic and biological), bimodal cancer cell imaging (by means of MRI and fluorescence), and bimodal cancer treatment (by targeted drug delivery and by hyperthermia effect). Nevertheless, for these concepts to work together, the choice of ingredients and particle structure are critically important. Therefore, in the present work, a detailed physicochemical characterization of the organic coating of the hybrid nanoparticles is performed by several surface-specific instrumental methods, including surface-enhanced Raman scattering (SERS) spectroscopy, X-ray photoelectron spectrometry (XPS), and time-of-flight secondary ion mass spectrometry (ToF-SIMS). We demonstrate that the anticancer drug doxorubicin is attached to the iron oxide surface and buried under the polymer layers, while folic acid is located on the extreme surface of the organic coating. Interestingly, the moderate presence of folic acid on the particle surface does not increase the particle surface potential, while it is sufficient to increase the particle uptake by MCF-7 cancer cells. All of these original results contribute to the better understanding of the structure-activity relationship for hybrid biocompatible nanosystems and are encouraging for the applications in cancer theranostics.     

Facile electrodeposition of ZnO on graphitic substrate for photocatalytic application: degradation of antibiotics in a continuous stirred-tank reactor

Journal of Solid State Electrochemistry - This work discusses the possibility of obtaining ZnO film on graphite, which can be widely used for photocatalysis, photocells, photodetectors, etc. The...     

Finite-time semistability,Filippov systems,and consensus protocols for nonlinear dynamical networks with switching topologies

This paper focuses on semistability and finite-time semistability for discontinuous dynamical systems. Semistability is the property whereby the solutions of a dynamical system converge to Lyapunov stable equilibrium points determined by the system initial conditions. In this paper, we extend the theory of semistability to discontinuous autonomous dynamical systems. In particular, Lyapunov-based tests for strong and weak semistability as well as finite-time semistability for autonomous differential inclusions are established. Using these results we then develop a framework for designing semistable and finite-time semistable protocols for dynamical networks with switching topologies. Specifically, we present distributed nonlinear static and dynamic output feedback controller architectures for multiagent network consensus and rendezvous with dynamically changing communication topologies.     

Antimicrobial Peptide Dendrimers and Quorum-Sensing Inhibitors in Formulating Next-Generation Anti-Infection Cell Therapy Dressings for Burns

Multidrug resistance infections are the main cause of failure in the pro-regenerative cell-mediated therapy of burn wounds. The collagen-based matrices for delivery of cells could be potential substrates to support bacterial growth and subsequent lysis of the collagen leading to a cell therapy loss. In this article, we report the development of a new generation of cell therapy formulations with the capacity to resist infections through the bactericidal effect of antimicrobial peptide dendrimers and the anti-virulence effect of anti-quorum sensing MvfR (PqsR) system compounds, which are incorporated into their formulation. Anti-quorum sensing compounds limit the pathogenicity and antibiotic tolerance of pathogenic bacteria involved in the burn wound infections, by inhibiting their virulence pathways. For the first time, we report a biological cell therapy dressing incorporating live progenitor cells, antimicrobial peptide dendrimers, and anti-MvfR compounds, which exhibit bactericidal and anti-virulence properties without compromising the viability of the progenitor cells.     

Photophysical and structural properties of cyanoruthenate complexes of hexaazatriphenylene

The tritopic bridging ligand hexaazatriphenylene (HAT) has been used to prepare the mono-, di-, and trinuclear cyanoruthenate complexes [Ru(CN)(4)(HAT)](2-) ([1](2-)), [{Ru(CN)(4)}(2)(mu(2)-HAT)](4-) ([2](4-)), and [{Ru(CN)(4)}(3)(mu(3)-HAT)](6-) ([3](6-)). These complexes are of interest both for their photophysical properties and ability to act as sensitizers, associated with strong MLCT absorptions; and their structural properties, with up to 12 externally directed cyanide ligands at a single "node" for preparation of coordination networks. The complexes are strongly solvatochromic, with broad and intense MLCT absorption manifolds arising from the presence of low-lying pi* orbitals on the HAT ligand, as confirmed by DFT calculations; in aprotic solvents [3](6-) is a panchromatic absorber of visible light. Although nonluminescent in fluid solution, the lowest MLCT excited states have lifetimes in D(2)O of tens of nanoseconds and could be detected by time-resolved IR spectrosocopy. For dinuclear [2](4-) and trinuclear [3](6-) the TRIR spectra are indicative of asymmetric MLCT excited states containing distinct Ru(III) and Ru(II) centers on the IR time scale. The complexes show red (3)MLCT luminescence as solids and in EtOH/MeOH glass at 77 K. Ln(III) salts of [1](2-), [2](4-), and [3](6-) form infinite coordination networks based on Ru-CN-Ln bridges with a range of one-, two-, and three-dimensional polymeric structures. In the Yb(III) and Nd(III) salts of [3](6- )the complex anion forms an 8-connected node. Whereas all of the Gd(III) salts show strong (3)MLCT luminescence in the solid state, the Ru-based emission in the Nd(III) and Yb(III) analogues is substantially quenched by Ru --> Ln photoinduced energy transfer, which results in sensitized near-infrared luminescence from Yb(III) and Nd(III).     

Probing the excited states of d6 metal complexes containing the 2,2'-bipyrimidine ligand using time-resolved infrared spectroscopy. 1. Mononuclear and homodinuclear systems

This paper reports time-resolved infrared (TRIR) spectroscopic studies on a series of weakly luminescent or nonluminescent 2,2'-bipyrimidine-based complexes to probe their electronic structure and the dynamic behavior of their excited states on the picosecond and nanosecond time scales. The complexes are mononuclear [Re(CO)3Cl(bpm)] (1), [Ru(CN)4(bpm)]2- (2), and [Ru(bpyam)2(bpm)]2+ (3) [bpm=2,2'-bipyrimidine; bpyam=2,2'-bipyridine-4,4'-(CONEt2)2] and their homodinuclear analogues [{Re(CO)3Cl}2(mu-bpm)] (4), [{Ru(CN)4}2(mu-bpm)]2- (5), and [{Ru(bpyam)2}2(mu-bpm)]4+ (6). Complex 1 shows the characteristic shift of the three nu(CO) bands to higher energy in the Re-->bpm triplet metal-to-ligand charge-transfer (3MLCT) state, which has a lifetime of 1.2 ns. In contrast, the dinuclear complex 4 shows nu(CO) transient bands to both higher and lower energy than the ground state indicative of, on the IR time scale, an asymmetric excited state [(OC)3ClReI(bpm*-)ReII(CO)3Cl] whose lifetime is 46 ps. The cyanoruthenate complexes 2 and 5 show comparable behavior, with a shift of the nu(CN) bands to higher energy in the excited state for mononuclear 2 but two sets of transient bands-one to higher energy and one to lower energy-in dinuclear 5, consistent with an asymmetric charge distribution [(NC)4RuII(bpm*-)RuIII(CN)4]4- in the 3MLCT state. These cyanoruthenate complexes have much longer lifetimes in D2O compared with CH3CN, viz., 250 ps and 3.4 ns for 2 and 65 ps and 1.2 ns for 5 in CH3CN and D2O, respectively. In complex 3, both higher-energy Ru-->bpyam and lower-energy Ru-->bpm 3MLCT states are formed following 400 nm excitation; the former decays rapidly (tau=6-7 ps) to the latter, and the subsequent decay of the Ru-->bpm 3MLCT state occurs with a lifetime of 60 or 97 ns in D2O or CH3CN, respectively. Similar behavior is shown by dinuclear 6 in both D2O and CH3CN, with initial interconversion from the Ru-->bpyam to the Ru-->bpm 3MLCT state occurring with tau approximately 7 ps and the resultant Ru-->bpm 3MLCT state decaying on the nanosecond time scale.     

Existence of two concomitant magnetic structures below T(Néel) for the natrochalcite, NaFe(II)2(H3O2)(MoO4)2

A comparative study of the magnetic properties and magnetic structures of the natrochalcite, NaFe(2)(D(3)O(2))(MoO(4))(2) (FeD) to those of the isostructural NaCo(2)(D(3)O(2))(MoO(4))(2) (CoD) and NaNi(2)(D(3)O(2))(MoO(4))(2) (NiD) is presented. The structural change is a shrinking of the unit cell in the order of the ionic radii of the transition metal, FeD > CoD > NiD. While NiD and CoD are canted-antiferromagnets with T(N) = 28 and 21 K, respectively, FeD is an anisotropic 2D-Ising antiferromagnet (T(N) = 17 K) with a spin-flop field of 14 kOe at 2 K and the presence of a hysteresis loop reaching only (1)/(4) of the saturation magnetization in 70 kOe. The critical field decreases almost linearly on warming to T(N). The neutron diffraction patterns of FeD below T(N) display numerous magnetic Bragg peaks which cannot be assigned to any one magnetic structure but fits well to two superposed sets, one with a temperature independent line width and has a propagation vector k(1) = (0, 0, 0) while for the other there is a clear dependence and k(2) = (0, 0, ?). In the k(1) = (0, 0, 0) magnetic structure the moments are parallel to each other within one chain and lie along the a-axis but are antiparallel to those in neighboring chains. In contrast CoD and NiD, for which k = (0, 0, 0), have their moments aligned along the b-axis and ac-plane, respectively. The second magnetic structure, k(2) = (0, 0, ?), is characterized by four sublattices, two per layer, where the moments are in the ab-plane and canted with a resultant along the a-axis which is compensated by those of the adjacent layers. For the k(2) = (0, 0, ?) structure, the scattering coherent length decreases, and the moments tend progressively toward the a-axis upon increasing temperature. The coexistence of two concomitant magnetic structures is unprecedented for compounds containing transition metal moment carriers.