S-p-bromobenzyl-glutathione cyclopentyl diester (BBGC) as novel therapeutic strategy to enhance trabectedin anti-tumor effect in soft tissue sarcoma preclinical models.

Trabectedin, approved for the treatment of soft tissue sarcoma (STS), interferes with cell division and genetic transcription processes. Due to its strong anti-tumor activity in only certain histotypes, several studies on trabectedin combinations are currently ongoing to improve its efficacy. In this study, we aimed to investigate novel potential therapeutic strategies to enhance the anti-tumor effect of trabectedin using integrated in silico, in vitro, and in vivo approaches. For in silico analysis, we screened two public datasets, GSEA M5190 and TCGA SARC. Fibrosarcoma, leiomyosarcoma, dedifferentiated, and myxoid liposarcoma cell lines were used for in vitro studies. For in vivo experiments, fibrosarcoma orthotopic murine model was developed. In silico analysis identified Glo1 as the only druggable target upregulated after trabectedin treatment and correlated with poor prognosis. The specific Glo1 inhibitor, S-p-bromobenzylglutathione cyclopentyl diester (BBGC), increased trabectedin cytotoxicity in STS cells, and restored drug sensitivity in myxoid liposarcoma cells resistant to trabectedin. Moreover, the combined treatment with BBGC and trabectedin had a synergistic antitumor effect in vivo without any additional toxicity to mice. Based on these results, we believe that BBGC warrants further investigation to evaluate its potential clinical use in combination with trabectedin.

Determinants of prolonged viral RNA shedding in hospitalized patients with SARS-CoV-2 infection.

OBJECTIVE: To evaluate determinants of prolonged viral RNA shedding in hospitalized patients with SARS-CoV-2 infection. MATERIALS AND METHODS: Hospitalized patients with SARS-CoV-2 positive nasopharyngeal RT-PCR were included in a single-center, retrospective study. Patients were divided in 2 groups according to the timing of viral clearance [≤14 days, "early clearance (EC)" and >14 days, "late clearance (LC)"]. RESULTS: 179 patients were included in the study (101 EC, 78 LC), with median age 62 years. Median time of viral shedding was 14 days (EC/LC 10 and 19 days, respectively, P < 0.0001). Univariate analyses showed that age, male gender, receiving corticosteroids, receiving tocilizumab, ICU admission, low albumin and NLR ratio were associated with late viral clearance. In the multivariable analysis, older age (P = 0.016), albumin level (P = 0.048), corticosteroids (P = 0.021), and tocilizumab (P = 0.015) were significantly associated with late viral clearance. CONCLUSIONS: Age, albumin, tocilizumab and corticosteroid treatment were independently associated with a prolonged SARS-CoV-2 RNA shedding.

Correlation of the Madelung constant and I-M-I bonding angle with cohesive energy contributions in layered metal diiodides (MI2) with CdI2 (2H polytype) structure.

This study uses theoretically methods to investigate, for metal diiodides MI2 (M = Mg, Ca, Mn, Fe, Cd, Pb) with CdI2 (2H polytype) structure, the mutual correlation between the structure-characterizing parameters (the flatness parameter of monolayers f, the Madelung constant A, and bonding angle I-M-I) and correlation of these parameters with contributions of the Coulomb and covalent energies to cohesive energy. The energy contributions to cohesive energy are determined with the use of empirical atomic potentials. It is demonstrated that the parameters f and A, and the bonding angle I-M-I are strictly correlated and increase in the same order: FeI2 < PbI2 < MnI2 < CdI2 < MgI2 < CaI2. It is found that with an increase of parameter A and bonding angle I-M-I the relative contribution of the Coulomb energy to cohesive energy increases, whereas the relative contribution of the covalent energy decreases. For a hypothetical MX2 layered compound with the CdI2 (2H polytype) structure, composed of regular MX6 octahedra (angle X-M-X = 90°), the flatness parameter and the Madelung constant are found to be freg = 2.449 and Areg = 2.183, respectively. Correlation of the covalent energy with the type of distortion of MI6 octahedra (elongation or compression) with respect to regular configuration (angle I-M-I = 90°) is also analyzed.

Engineering of entanglement and spin state transfer via quantum chains of atomic spins at large separations.

Several recent experiments have shown that long-range exchange interactions can determine collective magnetic ground states of nanostructures in bulk and on surfaces. The ability to generate and control entanglement in a system with long-range interaction will be of great importance for future quantum technology. An important step forward to reach this goal is the creation of entangled states for spins of distant magnetic atoms. Herein, the generation of long-distance entanglement between remote spins at large separations in bulk and on surface is studied theoretically, based on a quantum spin Hamiltonian and time-dependent Schrödinger equation for experimentally realized conditions. We demonstrate that long-distance entanglement can be generated between remote spins by using an appropriate quantum spin chain (a quantum mediator), composed by sets of antiferromagnetically coupled spin dimers. Ground state properties and quantum spin dynamics of entangled atoms are studied. We demonstrate that one can increase or suppress entanglement by adding a single spin in the mediator. The obtained result is explained by monogamy property of entanglement distribution inside a quantum spin system. We present a novel approach for non-local sensing of remote magnetic adatoms via spin entanglement.

Spectroscopic identification of the chemical interplay between defects and dopants in Al-doped ZnO.

The conduction and optoelectronic properties of transparent conductive oxides can be largely modified by intentional inclusion of dopants over a very large range of concentrations. However, the simultaneous presence of structural defects results in an unpredictable complexity that prevents a clear identification of chemical and structural properties of the final samples. By exploiting the unique chemical sensitivity of Hard X-ray Photoelectron Spectra and Near Edge X-ray Absorption Fine Structure in combination with Density Functional Theory, we determine the contribution to the spectroscopic response of defects in Al-doped ZnO films. Satellite peaks in O1s and modifications at the O K-edge allow the determination of the presence of H embedded in ZnO and the very low concentration of Zn vacancies and O interstitials in undoped ZnO. Contributions coming from substitutional and (above the solubility limit) interstitial Al atoms have been clearly identified and have been related to changes in the oxide stoichiometry and increased oxygen coordination, together with small lattice distortions. In this way defects and doping in oxide films can be controlled, in order to tune their properties and improve their performances.

Switching of spins and entanglement in surface-supported antiferromagnetic chains.

Previous experimental studies discovered universal growth of chains and nanowires of various chemical elements on a corrugated molecular network of Cu3N on the Cu(110). Herein, performing combined ab initio and quantum Hamiltonian studies we demonstrate that such chains can be used for a fast spin switching and entanglement generation by locally applied magnetic pulses. As an example, we show that in antiferromagnetic Co chains a strong entanglement between ends of chains occurs during spin switching. A novel parity effect in spin dynamics is reported. Even-numbered chains are found to exhibit significantly faster spin switching than odd-numbered counterparts. Moreover, at certain parameters of the system the dimerization effect in the spin dynamics of the chains was found. Our studies give a clear evidence that tailoring spin dynamics and entanglement can be achieved by magnetic fields and by tuning exchange interactions in supported chains.

Surgical margins for duodenopancreatectomy.

Microscopic residual tumor (R1) affects prognosis of resected pancreatic head cancer patients. Surgeon's ability, caseload and accuracy of pathological staging affect the rate of R1 resections. The goal of this study was to verify if a standardized histopathological workup of the specimen affects the rate of microscopic residual tumor after PD for cancer. Two groups of specimens were managed with (Group 1, Standardized Group, SG) or without (Group 2, Non Standardized Group, NSG) a standardized histopathological workup reported by the Royal College of Pathologists. Group 1 included 50 cases of PD for periampullary cancer treated between October 2010 and July 2012. Group 2 included 50 cases of PD for periampullary cancer treated between September 2005 and September 2010. The primary endpoint of the study was to verify the differences in terms of R1 rate in the two groups. Correlation between presence/absence of microscopic residual tumor status and local recurrence was also evaluated. The cohort of 100 patients consisted of 66 pancreatic ductal adenocarcinoma (PDAC) (SG: 35; NSG: 31), 15 distal common bile duct cancer (SG: 9; NSG: 6) and 19 cancer of the ampulla of Vater (SG: 6; NSG: 13). The rate of R1 resections resulted higher in the SG (66% vs 10%, p < 0.05). The rate of local recurrence did not differ in the two groups (NSG 23.4%, SG 27.6%). No relationships were found between R1 status and development of local recurrence in both groups. Local recurrence occurred in 20% of R1-NSG and in 34.3% of R1-SG. Our study showed that the standardized method determines a significant increase of R1 resection if compared with other non-standardized methods. This difference is due to the different definition of minimum clearance (0-mm- vs 1-mm rule). Even if not significantly, the standardized method seems to better discriminate the patients in terms of local recurrence risk after R1 vs R0 in SG (34 vs 11%) in comparison with R1 vs R0 in NSG (20 vs 27%).

AFM-based tribological study of nanopatterned surfaces: the influence of contact area instabilities.

Although the importance of morphology on the tribological properties of surfaces has long been proved, an exhaustive understanding of nanopatterning effects is still lacking due to the difficulty in both fabricating 'really nano-' structures and detecting their tribological properties. In the present work we show how the probe-surface contact area can be a critical parameter due to its remarkable local variability, making a correct interpretation of the data very difficult in the case of extremely small nanofeatures. Regular arrays of parallel 1D straight nanoprotrusions were fabricated by means of a low-dose focused ion beam, taking advantage of the amorphization-related swelling effect. The tribological properties of the patterns were detected in the presence of air and in vacuum (dry ambient) by atomic force microscopy. We have introduced a novel procedure and data analysis to reduce the uncertainties related to contact instabilities. The real time estimation of the radius of curvature of the contacting asperity enables us to study the dependence of the tribological properties of the patterns from their geometrical characteristics. The effect of the patterns on both adhesion and the coefficient of friction strongly depends on the contact area, which is linked to the local radius of curvature of the probe. However, a detectable hydrophobic character induced on the hydrophilic native SiO2 has been observed as well. The results suggest a scenario for capillary formation on the patterns.

Tuning magnetic properties of antiferromagnetic chains by exchange interactions: ab initio studies.

The possibility of using exchange interactions to manipulate the spin state of an antiferromagnetic nanostructure is explored using ab initio calculations. By considering M (M = Mn, Fe, Co) mono-atomic chains supported on Cu2N islands on a Cu(001) surface as a model system, it is demonstrated that two indistinguishable Néel states of an antiferromagnetic chain can be tailored into a preferred state by the exchange interaction with a magnetic STM tip. The magnitude and direction of the anisotropy for antiferromagnetic chains can also be tuned by exchange coupling upon varying the tip-chain separation.

Visualizing Non-abrupt Transition of Quantum Well States at Stepped Silver Surfaces.

We use scanning tunneling spectroscopy (STS) experiments and first-principles density functional theory (DFT) calculations to address a fundamental question of how quantum well (QW) states for electrons in a metal evolve spatially in the lateral direction when there is a surface step that changes the vertical confinement thickness. This study reveals a clear spatially dependent, nearly continuous trend in the energetic shifts of quantum well (QW) states of thin Ag(111) film grown on Cu(111) substrate, showing the strongest change near the step edge. A large energetic shift equaling up to ~200 meV with a lateral extension of the QW states of the order of ~20 Å is found, even though the step-edge is atomically sharp as evidenced by a line scan. The observed lateral extension and the nearly smooth transition of QW states are understood within the context of step-induced charge oscillation, and Smoluchowski-type charge spreading and smoothing.

Nanoscale frictional behavior of graphene on SiO2 and Ni(111) substrates.

Friction characteristics of graphene deposited on different substrates have been studied by atomic force microscopy (AFM). In particular, we compared mechanically exfoliated graphene transferred over Si/SiO2 with respect to monolayer (ML) graphene grown in our laboratory by low temperature chemical vapor deposition on Ni(111) single crystal. Friction force measurements by AFM have been carried out as function of load under different environment conditions, namely vacuum (10(-5) Torr), nitrogen and air. The typical decrease of friction force with increasing number of layers has been observed on graphene over Si/SiO2 in all environment including vacuum. Continuum mechanical approximation has been used to analyze the friction versus load curves of ML graphene on Ni(111). Analysis shows that Derjaguin-Mueller-Toporov model is in good agreement with our experimental data indicating that overall behavior of the interface graphene-Ni(111) is relatively rigid respect to out of plane deformations. This result is consistent with the structural characteristics of the interface since graphene grows in registry with Ni(111) surface with covalent bonding character. Finally, the shear strength and the work of adhesion of the two systems with respect to AFM tip in vacuum have been compared. The result of this procedure indicates that shear strength and work of adhesion measured on graphene-Si/SiO2 interface are always greater than those on graphene-Ni(111) interface.

Tuning an Atomic Switch on a Surface with Electric and Magnetic Fields.

Controllable switching an adatom position and its magnetization could lead to a single-atom memory. Our theoretical studies show that switching adatom between different surface sites by the quantum tunneling, discovered in several experiments, can be controlled by an external electric field. Switching a single spin by magnetic fields is found to be strongly site-dependent on a surface. This could enable to control a spin-dynamics of adatom.

Regio- and stereoselective synthesis of new diaminocyclopentanols.

The optimal conditions for regio- and stereoselective epoxide ring opening of N,N-disubstituted 1,2-epoxy-3-aminocyclopentanes by different nucleophilic reagents have been developed. The substituents on the nitrogen atom in the epoxide precursor and the orientation of the oxirane ring are crucial for the reaction outcome. Thus, treatment of (1RS,2SR,3SR)-1,2-epoxy-3-(N,N-dibenzylamino)cyclopentane (3b) with amines gave a mixture of C1 and C2 regioadducts, while the use of (1RS,2SR,3SR)-1,2-epoxy-3-(N-benzyl-N-methylamino)cyclopentane (3a) led ultimately to C1 adducts. Base-catalyzed aminolysis of epoxides 6a,b afforded mainly C1 adducts 13a,b arising from trans-diaxal opening of the epoxide ring. Using a Lewis acid catalyst, epoxides 6a,b were transformed into diaminocyclopentanols 14a,b via an alternative pathway involving the formation of aziridinium intermediate 17.

Complete pathological response after FOLFIRINOX for locally advanced pancreatic cancer. The beginning of a new era? Case report and review of the literature.

Neoadjuvant treatments (chemo or chemoradiation therapy) are used for patients with locally advanced Pancreatic Ductal Adeno-Carcinoma (PDAC). FOLFIRINOX is now considered an effective treatment modality for patients with metastatic pancreatic cancer and a promising option for patients with locally advanced PDAC. Complete pathologic response after neoadjuvant therapies is anecdotic and its prognostic impact is completely unclear. We report the case of a complete pathological response after treatment with FOLFIRINOX in a patient affected by a locally advanced PDAC with a review of the literature regarding the use of FOLFIRINOX for locally advanced PDAC.

Electronic and magnetic properties at the edges of nanostructures in an electric field: ab initio study.

State of the art ab initio calculations of the electronic and magnetic properties at the edges of magnetic nanostructures in an external electric field are presented in this paper. Our results for the Fe stripes on Fe(0 0 1) reveal the existence of spin-polarized edge states. A spatially inhomogeneous electronic structure is found at the edge. We demonstrate that the spin-dependent screening density varies greatly at the atomic scale. Tuning of the spin-polarization by the external electric field is demonstrated.

Structural and morphological modifications of thermally reduced cerium oxide ultrathin epitaxial films on Pt(111).

The modifications of the stoichiometry, morphology and surface structure of cerium oxide ultrathin films induced by thermal treatments under vacuum and oxygen partial pressure were studied using in situ X-ray photoemission spectroscopy, scanning tunnelling microscopy and low energy electron diffraction. The effect of the film nominal thickness, heating temperature and heating time on the degree of reduction of the film was investigated. The reduction is more relevant on the film surface, where different ordered surface structures were observed at different degrees of reduction for very thin films. The obtained results are discussed taking into account the dimensionality of the oxide and the effects of the proximity of the Pt substrate. After reduction it was always possible to re-oxidize the films back to their original oxidation state by thermal treatment under oxygen-rich conditions.

Electric field for tuning quantum entanglement in supported clusters.

We show that quantum entanglement, nowadays so widely observed and used in a multitude of systems, can be traced in the atomic spins of metal clusters supported on metal surfaces. Most importantly, we show that it can be voluntarily altered with external electric fields. We use a combination of ab initio and model Heisenberg-Dirac-Van Vleck quantum spin Hamiltonian calculations to show, with the example of a prototype system (Mn dimers on Ag(0 0 1) surface), that, in an inherently unentangled system an electric field can 'switch on' the entanglement and significantly change its critical temperature parameter. The physical mechanism allowing such rigorous control of entanglement by an electric field is the field-induced change in the internal magnetic coupling of the supported nanostructure.

Controlling magnetism on metal surfaces with non-magnetic means: electric fields and surface charging.

We review the state of the art of surface magnetic property control with non-magnetic means, concentrating on metallic surfaces and techniques such as charge-doping or external electric field (EEF) application. Magneto-electric coupling via EEF-based charge manipulation is discussed as a way to tailor single adatom spins, exchange interaction between adsorbates or anisotropies of layered systems. The mechanisms of paramagnetic and spin-dependent electric field screening and the effect thereof on surface magnetism are discussed in the framework of theoretical and experimental studies. The possibility to enhance the effect of EEF by immersing the target system into an electrolyte or ionic liquid is discussed by the example of substitutional impurities and metallic alloy multilayers. A similar physics is pointed out for the case of charge traps, metallic systems decoupled from a bulk electron bath. In that case the charging provides the charge carrier density changes necessary to affect the magnetic moments and anisotropies in the system. Finally, the option of using quasi-free electrons rather than localized atomic spins for surface magnetism control is discussed with the example of Shockley-type metallic surface states confined to magnetic nanoislands.