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At least 415 records · Page 23

Nucleolin is expressed in patient-derived samples and glioblastoma cells, enabling improved intracellular drug delivery and cytotoxicity

Highlights: • Nucleolin is overexpressed in GSC sub-populations and non-stem glioblastoma cells; • Nucleolin enables intracellular targeted drug delivery in glioblastoma cells; • Nucleolin is overexpressed in glioblastoma patient-derived samples. One of the major challenges in Glioblastoma (GBM) therapy relates with the existence of glioma stem-like cells (GSCs), known to be chemo- and radio-resistant. GSCs and non-stem GBM cells have the ability to interchange, emphasizing the importance of identifying common molecular targets among those cell sub-populations. Nucleolin overexpression has been recently associated with breast cancer sub-populations with different stem-like phenotype. The goal of this work was to evaluate the potential of cell surface nucleolin as a target in GBM cells. Different levels of nucleolin expression resulted in a 3.4-fold higher association of liposomes targeting nucleolin (functionalized with the nucleolin-binding F3 peptide) in U87, relative to GBM11 glioblastoma cells. Moreover, nucleolin was suggested as a potential marker in OCT4-, NANOG-positive GSC, and in the corresponding non-stem GBM cells, as well as in SOX2-positive GSC. Doxorubicin delivered by liposomes targeting nucleolin enabled a level of cytotoxicity that was 2.5- or 4.6-fold higher compared to the non-targeted counterparts. Importantly, an overexpression of nucleolin was also observed in cells of patient-derived samples, as compared with normal brain. Overall, these results suggested nucleolin as a therapeutic target in GBM.

60 APPLIED LIFE SCIENCES↗

Effects of ionizing radiation and HPSE1 inhibition on the invasion of oral tongue carcinoma cells on human extracellular matrices in vitro

Highlights: • Myoma-based ECM models are suitable for in vitro chemoradiation assays. • Blocking of HPSE1 activity combined with IR may induce tongue cancer cell invasion. • Low doses of IR may increase MMP expression and invasion in tongue cancer cells. Chemoradiation is an established approach in the treatment of advanced oral tongue squamous cell carcinoma (OTSCC), but therapy may cause severe side-effects due to signal interchanges between carcinoma and the tumour microenvironment (TME). In this study, we examined the potential use of our human 3D myoma disc and Myogel models in in vitro chemoradiation studies by analysing the effects of ionizing radiation (IR) and the combined effect of heparanase I (HPSE1) inhibitors and IR on OTSCC cell proliferation, invasion and MMP-2 and − 9 production. Finally, we analysed the long-term effects of IR by studying clones of previously irradiated and invaded HSC-3 cells. We found that in both human uterine leiomyoma-based extracellular matrix models IR inhibited the invasion of HSC-3 cells, but blocking HPSE1 activity combined with IR induced their invasion. Low doses of IR increased MMP expression and initiated epithelial-mesenchymal transition in cells cultured on myoma discs. We conclude that myoma models offer consistent methods for testing human carcinoma cell invasion and phenotypic changes during chemoradiation treatment. In addition, we showed that IR had long-term effects on MMP-2 and − 9, which might elicit different HSC-3 invasion responses when cells were under the challenge of HPSE1 inhibitors and IR.

60 APPLIED LIFE SCIENCES↗

The on-axis magnetic well and Mercier's criterion for arbitrary stellarator geometries

A simplified analytical form of the on-axis magnetic well and Mercier's criterion for interchange instabilities for arbitrary three-dimensional magnetic field geometries is derived. For this purpose, a near-axis expansion based on a direct coordinate approach is used by expressing the toroidal magnetic flux in terms of powers of the radial distance to the magnetic axis. For the first time, the magnetic well and Mercier's criterion are then written as a one-dimensional integral with respect to the axis arclength. When compared with the original work of Mercier, the derivation here is presented using modern notation and in a more streamlined manner that highlights essential steps. Finally, these expressions are verified numerically using several quasisymmetric and non-quasisymmetric stellarator configurations including Wendelstein 7-X.

Physics↗

Physics basis for the Wisconsin HTS Axisymmetric Mirror (WHAM)

The Wisconsin high-temperature superconductor axisymmetric mirror experiment (WHAM) will be a high-field platform for prototyping technologies, validating interchange stabilization techniques and benchmarking numerical code performance, enabling the next step up to reactor parameters. A detailed overview of the experimental apparatus and its various subsystems is presented. WHAM will use electron cyclotron heating to ionize and build a dense target plasma for neutral beam injection of fast ions, stabilized by edge-biased sheared flow. At 25 keV injection energies, charge exchange dominates over impact ionization and limits the effectiveness of neutral beam injection fuelling. This paper outlines an iterative technique for self-consistently predicting the neutral beam driven anisotropic ion distribution and its role in the finite beta equilibrium. Beginning with recent work by Egedal et al. ( Nucl. Fusion , vol. 62, no. 12, 2022, p. 126053) on the WHAM geometry, we detail how the FIDASIM code is used to model the charge exchange sources and sinks in the distribution function, and both are combined with an anisotropic magnetohydrodynamic equilibrium solver method to self-consistently reach an equilibrium. We compare this with recent results using the CQL3D code adapted for the mirror geometry, which includes the high-harmonic fast wave heating of fast ions.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Asymptotic quasisymmetric high-beta three-dimensional magnetohydrodynamic equilibria near axisymmetry

Quasisymmetry (QS), a hidden symmetry of the magnetic field strength, is known to support nested flux surfaces and provide superior particle confinement in stellarators. In this work, we study the ideal magnetohydrodynamic (MHD) equilibrium and stability of high-beta plasma in a large-aspect-ratio stellarator. In particular, we show that the lowest-order description of a near-axisymmetric equilibrium vastly simplifies the problem of three-dimensional quasisymmetric MHD equilibria, which can be reduced to a standard elliptic Grad–Shafranov equation for the flux function. We show that any large-aspect-ratio tokamak, deformed periodically in the vertical direction, is a stellarator with approximate volumetric QS. We discuss exact analytical solutions and numerical benchmarks. Finally, we discuss the ideal ballooning and interchange stability of some of our equilibrium configurations.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Metastability of stratified magnetohydrostatic equilibria and their relaxation

Motivated by explosive releases of energy in fusion, space and astrophysical plasmas, we consider the nonlinear stability of stratified magnetohydrodynamic equilibria against two-dimensional interchanges of straight magnetic-flux tubes. We demonstrate that, even within this restricted class of dynamics, the linear stability of an equilibrium does not guarantee its nonlinear stability: equilibria can be metastable. We show that the minimum-energy state accessible to a metastable equilibrium under non-diffusive two-dimensional dynamics can be found by solving a combinatorial optimisation problem. These minimum-energy states are, to good approximation, the final states reached by our simulations of destabilised metastable equilibria for which turbulent mixing is suppressed by viscosity. To predict the result of fully turbulent relaxation, we construct a statistical mechanical theory based on the maximisation of Boltzmann's mixing entropy. This theory is analogous to the Lynden-Bell statistical mechanics of collisionless stellar systems and plasma, and to the Robert–Sommeria–Miller theory of two-dimensional vortex turbulence. Our theory reproduces well the results of our numerical simulations for sufficiently large perturbations to the metastable equilibrium.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Modular Homogeneous Chromophore–Catalyst Assemblies

Photosynthetic reaction center (RC) proteins convert incident solar energy to chemical energy through a network of molecular cofactors which have been evolutionarily tuned to couple efficient light-harvesting, directional electron transfer, and long-lived charge separation with secondary reaction sequences. These molecular cofactors are embedded within a complex protein environment which precisely positions each cofactor in optimal geometries along efficient electron transfer pathways with localized protein environments facilitating sequential and accumulative charge transfer. By contrast, it is difficult to approach a similar level of structural complexity in synthetic architectures for solar energy conversion. However, by using appropriate self-assembly strategies, we anticipate that molecular modules, which are independently synthesized and optimized for either light-harvesting or redox catalysis, can be organized into spatial arrangements that functionally mimic natural photosynthesis. In this Account, we describe a modular approach to new structural designs for artificial photosynthesis which is largely inspired by photosynthetic RC proteins. We focus on recent work from our lab which uses molecular modules for light-harvesting or proton reduction catalysis in different coordination geometries and different platforms, spanning from discrete supramolecular assemblies to molecule–nanoparticle hybrids to protein-based biohybrids. Molecular modules are particularly amenable to high-resolution characterization of the ground and excited state of each module using a variety of physical techniques; such spectroscopic interrogation helps our understanding of primary artificial photosynthetic mechanisms. In particular, we discuss the use of transient optical spectroscopy, EPR, and X-ray scattering techniques to elucidate dynamic structural behavior and light-induced kinetics and the impact on photocatalytic mechanism. Two different coordination geometries of supramolecular photocatalyst based on the [Ru(bpy)3]2+ (bpy = 2,2'-bipyridine) light-harvesting module with cobaloxime-based catalyst module are compared, with progress in stabilizing photoinduced charge separation identified. These same modules embedded in the small electron transfer protein ferredoxin exhibit much longer charge-separation, enabled by stepwise electron transfer through the native [2Fe-2S] cofactor. We anticipate that the use of interchangeable, molecular modules which can interact in different coordination geometries or within entirely different structural platforms will provide important fundamental insights into the effect of environment on parameters such as electron transfer and charge separation, and ultimately drive more efficient designs for artificial photosynthesis.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Observation of Vacancies, Faults, and Superstructures in Ln 5 Mo 2 O 12 (Ln = La, Y, and Lu) Compounds with Direct Mo–Mo Bonding

Among oxide compounds with direct metal–metal bonding, the Y 5 Mo 2 O 12 (A 5 B 2 O 12 ) structural family of compounds has a particularly intriguing low-dimensional structure due to the presence of bioctahedral B 2 O 10 dimers arranged in one-dimensional edge-sharing chains along the direction of the metal–metal bonds. Furthermore, these compounds can have a local magnetic moment due to the noninteger oxidation state (+4.5) of the transition metal, in contrast to the conspicuous lack of a local moment that is commonly observed when oxide compounds with direct metal–metal bonding have integer oxidation states resulting from the lifting of orbital degeneracy typically induced by the metal–metal bonding. Although a monoclinic C2/m structure has been previously proposed for Ln 5 Mo 2 O 12 (Ln = La–Lu and Y) members of this family based on prior single crystal diffraction data, it is found that this structural model misses many important structural features. On the basis of synchrotron powder diffraction data, it is shown in this paper that the C2/m monoclinic unit cell represents a superstructure relative to a previously unrecognized orthorhombic Immm subcell and that the superstructure derives from the ordering of interchangeable Mo 2 O 10 and LaO 6 building blocks. The superstructure for this reason is typically highly faulted, as evidenced by the increased breadth of superstructure diffraction peaks associated with a coherence length of 1–2 nm in the c* direction. Finally, it is shown that oxygen vacancies can occur when Ln = La, producing an oxygen deficient stoichiometry of La 5 Mo 2 O 11.55 and an approximately 10-fold reduction in the number of unpaired electrons due to the reduction of the average Mo valence from +4.5 to +4.05, a result confirmed by magnetic susceptibility measurements. Finally, this represents the first observation of oxygen vacancies in this family of compounds and provides an important means of continuously tuning the magnetic interactions within the one-dimensional octahedral chains of this system.

36 MATERIALS SCIENCE↗

Design of Metal-Halide Inverse-Hybrid Perovskites

We recently introduced a new class of perovskites, with inorganic anions on the A - and B -sites and an organic cation on the X -site, the so-called inverse-hybrid perovskites (IHPs). We found compounds that are predicted to be stable, possess large polarization, and span a wide range of electronic properties. Here, we present the materials search strategy that enabled these results. We demonstrate the design principles in terms of ion and site composition. Overall, we consider elements from most main groups of the periodic table, investigating their ability to form mono- or divalent anions in the framework of IHPs. We observe structural changes based on tolerance factor. Compounds are found in the perovskite or the related CaIrO3 structure, and different orientations of the employed organic cation (methylammonium) lead to different B···X···B bridging motifs. Furthermore, we demonstrate how the perovskite structure can be favored by interchanging B - and A -site anions and adjusting the ions within groups of the periodic table accordingly. Besides chalcogenide halides, we find that elements of groups XIII to XV can successfully form mono- or divalent anions by partly filling their valence p shell. Spin–orbit coupling in the heavier elements leads to interesting electronic motifs. Here, while light divalent elements show a tendency toward protonation, this is suppressed by employing heavier elements of the same group. Evaluating the stability of these novel compounds also requires us to investigate largely unknown methylammonium compounds with mono- and divalent anions.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Elucidating Structure–Spectral Property Relationships of Negative Thermal Expansion Zr 2 (WO 4 )(PO 4 ) 2 : A First-Principles Study with Experimental Validation

The phonon, infrared, and Raman spectroscopic properties of zirconium tungsten phosphate, Zr 2 (WO 4 )(PO 4 ) 2 (space group Pbcn , IT No. 60; Z = 4), have been extensively investigated using density functional perturbation theory (DFPT) calculations with the Perdew, Burke, and Ernzerhof exchange–correlation functional revised for solids (PBEsol) and validated by experimental characterization of Zr 2 (WO 4 )(PO 4 ) 2 prepared by hydrothermal synthesis. Using DFPT-simulated infrared, Raman, and phonon density-of-state spectra combined with Fourier transform infrared and Raman measurements, new comprehensive and extensive assignments have been made for the spectra of Zr 2 (WO 4 )(PO 4 ) 2 , resulting in the characterization of its 29 and 34 most intense IR- and Raman-active modes, respectively. DFPT results also reveal that ν 1 (PO 4 ) symmetric stretching and ν 3 (PO 4 ) antisymmetric stretching bands have been interchanged in previous Raman experimental assignments. Negative thermal expansion in Zr 2 (WO 4 )(PO 4 ) 2 appears to have very limited impact on the spectral properties of this compound. Furthermore, this work shows the high accuracy of the PBEsol exchange–correlation functional for studying the spectroscopic properties of crystalline materials using first-principles methods.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Visible-Light-Driven Triplet Sensitization of Polycyclic Aromatic Hydrocarbons Using Thionated Perinones

Metal-free chromophores that efficiently generate triplet excited states represent enticing alternatives with respect to transition metal-containing photosensitizers, such as those featuring metal-to-ligand charge transfer excited states. Yet, such molecular constructs have remained underexplored due to the unclear relationship(s) between molecular structure and efficient/rapid intersystem crossing. In this regard, we present a series of three thionated perinone chromophores serving as a newly conceived class of heavy metal-free triplet photosensitizers. We demonstrate that thionation of the lone C=O substituent in each highly fluorescent perinone imparts red-shifted absorbance bands that maintain intense extinction coefficients across the visible spectrum, as well as unusually efficient triplet excited state formation as inferred from the measured singlet O 2 quantum yields at 1270 nm (Φ Δ = 0.78–1.0). Electronic structure calculations revealed the emergence of a low energy S 1 (n → π*) excited state in the proximity of a slightly higher energy S 2 (π → π*) excited state. The distinct character in each of the two lowest-lying singlet state manifolds resulted in the energetic inversion of the corresponding triplet excited states due to differences in electron exchange interactions. Rapid S 1 → T 1 intersystem crossing was thereby facilitated in this manner through spin–orbit coupling as predicted by the El Sayed rules. The lifetimes of the resultant triplet excited states persisted into the microsecond time regime, as measured by transient absorbance spectroscopy, enabling effective bimolecular triplet sensitization of some common polycyclic aromatic hydrocarbons. The synthetically facile interchange of a single O atom to an S atom in the investigated perinones resulted in marked changes to their photophysical properties, namely, conversion of dominant singlet state fluorescence in the former to long-lived triplet excited states in the latter. The combined results suggest a general strategy for accessing long-lived triplet excited states in organic chromophores featuring a lone C=O moiety residing within its structure, valuable for the design of metal-free triplet photosensitizers.

14 SOLAR ENERGY↗

Interference of interchromophoric energy-transfer pathways in π-conjugated macrocycles

The interchromophoric energy-transfer pathways between weakly coupled units in a π-conjugated phenylene–ethynylene macrocycle and its half-ring analogue have been investigated using the nonadiabatic excited-state molecular dynamics approach. To track the flow of electronic transition density between macrocycle units, we formulate a transition density flux analysis adapted from the statistical minimum flow method previously developed to investigate vibrational energy flow. Following photoexcitation, transition density is primarily delocalized on two chromophore units and the system undergoes ultrafast energy transfer, creating a localized excited state on a single unit. In the macrocycle, distinct chromophore units donate transition density to a single acceptor unit but do not interchange transition density among each other. We find that energy transfer in the macrocycle is slower than in the corresponding half ring because of the presence of multiple interfering energy-transfer pathways. Finally, simulation results are validated by modeling the fluorescence anisotropy decay.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Reversible Interlayer Sliding and Conductivity Changes in Adaptive Tetrathiafulvalene-Based Covalent Organic Frameworks

Ordered interlayer stacking is intrinsic in two-dimensional covalent organic frameworks (2D COFs) and has strong implications on COF's optoelectronic properties. Reversible interlayer sliding, corresponding to shearing of 2D layers along their basal plane, is an appealing dynamic control of both structures and properties, yet it remains unexplored in the 2D COF field. In this paper, we demonstrate that the reversible interlayer sliding can be realized in an imine-linked tetrathiafulvalene (TTF)-based COF TTF-DMTA. The solvent treatment induces crystalline phase changes between the proposed staircase-like sql net structure and a slightly slipped eclipsed sql net structure. The solvation-induced crystallinity changes correlate well with reversible spectroscopic and electrical conductivity changes as demonstrated in oriented COF thin films. In contrast, no reversible switching is observed in a related TTF-TA COF, which differs from TTF-DMTA in terms of the absence of methoxy groups on the phenylene linkers. This work represents the first 2D COF example of which eclipsed and staircase-like aggregated states are interchangeably accessed via interlayer sliding, an uncharted structural feature that may enable applications such as chemiresistive sensors.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Exchange of Ions across the TiN/TaO x Interface during Electroformation of TaO x -Based Resistive Switching Devices

The valence change model describes the resistive switching in metal oxide-based devices as due to electroreduction of the oxide and subsequent electromigration of oxygen vacancies. Here, we present cross-sectional X-ray energy-dispersive spectroscopy elemental maps of Ta, O, N, and Ti in electroformed TiN/TaO 2.0 /TiN structures. O, N, and Ti were exchanged between the anode and the functional oxide in devices formed at high power (~1 mW), but the exchange was below the detection limit at low power (<0.5 mW). All structures exhibit a similar Ta-enriched and O-depleted filament formed by the elemental segregation in the functional oxide by the temperature gradient. The elemental interchange is interpreted as due to Fick’s diffusion caused by high temperatures in the gap of the filament and is not an essential part of electroformation.

36 MATERIALS SCIENCE↗

Thermally Stable Perovskite Solar Cells by Systematic Molecular Design of the Hole-Transport Layer

With the burgeoning performance of metal halide perovskite solar cells (PSC), one of the biggest challenges to date is addressing device stability. Within the PSC device stack, charge-selective contact selection has been shown to considerably impact PSC stability. Recently, a triarylamine-based hole-transport layer (HTL) doped with its oxidized organic salt analogue (EH44/EH44-ox) has been shown to bypass the need for hygroscopic lithium salt dopants, enabling high PSC stability in ambient conditions. Despite these promising results, the improved stability came with a power conversion efficiency (PCE) penalty and poor performance above 30 degrees C. Broadening the applicability and understanding of this under-utilized dopant system, we report design criteria for stable, synthetically simple triarylamine-based organic hole transport materials (HTM) and their corresponding oxidized salts as HTL dopants for improved PSC efficiency and stability at elevated temperature. The triarylamine-based dopants must contain at least two para-electron donating groups for radical cation stabilization to prevent impurity formation (e.g., dopant reduction) which significantly reduces PSC fill factors (FF) and PCE. To further improve PSC FF and PCE, these dopants can be interchanged with respect to the HTL matrix. The stability of unencapsulated devices prepared with these three new HTLs, under constant load and illumination, considerably outperform both EH44/EH44-ox and Li+-doped spiro-OMeTAD controls at 50 degrees C. The ability to mix and match a stable dopant with a non-identical small-molecule-based HTL matrix for improved charge-transport properties broadens design scope for highly stable and cost-effective PSC without sacrificing performance.

14 SOLAR ENERGY↗

Comparative Pore Structure and Dynamics for Bacterial Microcompartment Shell Protein Assemblies in Sheets or Shells

Bacterial microcompartments (BMCs) are protein-bound organelles found in some bacteria that encapsulate enzymes for enhanced catalytic activity. These compartments spatially sequester enzymes within semipermeable shell proteins, analogous to many membrane-bound organelles. The shell proteins assemble into multimeric tiles; hexamers, trimers, and pentamers, and these tiles self-assemble into larger assemblies with icosahedral symmetry. While icosahedral shells are the predominant form in vivo , the tiles can also form nanoscale cylinders or sheets. The individual multimeric tiles feature central pores that are key to regulating transport across the protein shell. Our primary interest is to quantify pore shape changes in response to alternative component morphologies at the nanoscale. We used molecular modeling tools to develop atomically detailed models for both planar sheets of tiles and curved structures representative of the complete shells found in vivo . Subsequently, these models were animated using classical molecular dynamics simulations. From the resulting trajectories, we analyzed the overall structural stability, water accessibility to individual residues, water residence time, and pore geometry for the hexameric and trimeric protein tiles from the Haliangium ochraceu m model BMC shell. These exhaustive analyses suggest no substantial variation in pore structure or solvent accessibility between the flat and curved shell geometries. We additionally compare our analysis to hydroxyl radical footprinting data to serve as a check against our simulation results, highlighting specific residues where water molecules are bound for a long time. Although with little variation in morphology or water interaction, we propose that the planar and capsular morphology can be used interchangeably when studying permeability through BMC pores.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Arene Substitution Design for Controlled Conformational Changes of Dibenzocycloocta-1,5-dienes

We report that the agile eight-mernbered cycloalkane can be stabilized by fusing two rigid benzene rings, substituted with proper functional groups. The conformational change of dibenzocycloocta-1,S-diene (DBCOD), a rigid-flexible-rigidorganic moiety, from Boat to Chair conformation requires an activation energy of 42 kJ/mol that is substantially lower than that of existing submolecular shape-changing unit. Experimental data corroborated by theory calculations demonstrate that intramolecular hydrogen bonding can stabilize Boat whereas electron repulsive interaction from opposing ester substituents favors Chair. Intramolecular hydrogen bonding, formed by 1,10-diamide substitution stabilizes Boat, spiking the temperature at which Boat and Chair can readily interchange from -60 °C to 60 °C. Concomitantly this intramolecular attraction raises the energy barrier from 42 kJ/mol of unsubstituted DBCOD to 68 kJ/mol of diamide-substituted DBCOD. Remarkably, this value falls within the range of the activation energy of highly efficient enzyme catalyzed biological reactions. With shape changes once considered only possible with high-energy, our work reveals a potential pathway exemplified by a specific submolecular structure to achieve low-energy driven shape changes for the first time. Together with intrinsic cycle stability and high energy output systems that would have incurred damage under high-energy stimuli, could particularly benefit from this new kind of low-energy driven shape-changing mechanism. This work has laid the basis to construct systems for low-energy driven stimuli-responsive applications, hitherto a challenge to overcome.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗