Interlayer and Intralayer Excitons in AlN/WS2 Heterostructure

The study of intra and interlayer excitons in 2D semiconducting vdW heterostructures is a very hot topic not only from a fundamental but also an applicative point of view. Due to their strong light–matter interaction, Transition Metal Dichalcogenides (TMD) and group-III nitrides are particularly attractive in the field of opto-electronic applications such as photo-catalytic and photo-voltaic ultra-thin and flexible devices. Using first-principles ground and excited-state simulations, we investigate here the electronic and excitonic properties of a representative nitride/TMD heterobilayer, the AlN/WS2. We demonstrate that the band alignment is of type I, and low energy intralayer excitons are similar to those of a pristine WS2 monolayer. Further, we disentangle the role of strain and AlN dielectric screening on the electronic and optical gaps. These results, although they do not favor the possible use of AlN/WS2 in photo-catalysis, as envisaged in the previous literature, can boost the recently started experimental studies of 2D hexagonal aluminum nitride as a good low screening substrate for TMD-based electronic and opto-electronic devices. Importantly, our work shows how the inclusion of both spin-orbit and many-body interactions is compulsory for the correct prediction of the electronic and optical properties of TMD/nitride heterobilayers.     

Anti-atherosclerotic action of GW9508 – Free fatty acid receptors activator – In apoE-knockout mice

BackgroundIn the past two decades, enhanced understanding of the biology of G-protein-coupled receptors (GPRs) has led to the identification of several such receptors as novel targets for free fatty acids (FFAs). Two GPRs, FFAR1 and FFAR4, have received special attention in the context of chronic inflammatory diseases, thanks to their anti-inflammatory activities.MethodsThe present study investigates the influence of prolonged treatment with GW9508 – agonist of FFAR1 and FFAR4 – on the development of atherosclerosis plaque in apoE-knockout mice, using morphometric and molecular methods.ResultsGW9508 administration has led to the reduction of atheroscletoric plaque size in an apoE-knockout mice model. Moreover, a FFAR1/FFAR4 agonist reduced the content of macrophages by almost 20%, attributed by immunohistochemical phenotyping to the pro-inflammatory M1-like activation state macrophages.ConclusionsProlonged administration of GW9508 resulted in significant amelioration of atherogenesis, providing evidence that the strategy based on macrophage phenotype switching toward an M2-like activation state via stimulation of FFAR1/FFAR4 receptors holds promise for a new approach to the prevention or treatment of atherosclerosis.     

TACE inhibition: a new approach to treating inflammation

Clinical trials showing the benefits of reducing the effects of TNF-α in rheumatoid arthritis have highlighted the key role of the cytokine TNF-α in this inflammatory condition. A new approach to reducing the effects of TNF-α is to decrease its synthesis by inhibiting TNF-α converting enzyme with GW3333. In rat models of arthritis, GW3333 has some beneficial effects. Further longer-term studies of GW3333 in animal models are required to determine whether its benefit is maintained. TACE inhibition may represent a new approach to treating inflammation.     

Polo-like kinase 1 inhibitors in mono- and combination therapies: a new strategy for treating malignancies

Polo-like kinase 1 (Plk1) inhibitors belong to a new class of drugs for the treatment of malignant diseases. They selectively act against a target (Plk1) which is involved in different stages of mitosis such as centrosome maturation, spindle formation, chromosome separation and cytokinesis. Because Plk1 is mainly expressed in proliferating tissues and overexpressed in cancers, its inhibition is potentially less prone to toxicities associated with current antimitotic agents, which also act on nondividing cells. Several Plk1 inhibitors are being evaluated as cancer treatment drugs. Based on the essential role of Plk1 during mitosis, Plk1 inhibitors target all rapidly dividing cells irrespective of their tumor suppressor or oncogene mutations. In this article, their mechanisms of action, efficacy and toxicity profile are discussed.     

Novel glucocorticoid receptor agonists in the treatment of asthma

Introduction: Inhaled corticosteroids are the only drugs that effectively suppress the airway inflammation, but they can induce considerable systemic and adverse effects when they are administered chronically at high doses. Consequently, the pharmaceutical industry is still searching for newer entities with an improved therapeutic index.

Areas covered: Herein, the authors review the research in the glucocorticoid field to identify ligands of the glucocorticoid receptor (GR). These ligands preferentially induce transrepression with little or no transactivating activity, in order to have a potent anti-inflammatory action and a low side-effects profile.

Expert opinion: Several agents have been synthesized, but few have been tested in experimental models of asthma. Furthermore, only three (BI-54903, GW870086X and AZD5423) have entered clinical development, although the development of at least one of them (BI-54903) was discontinued. The reason for the limited success so far obtained is that the model of transactivation versus transrepression is a too simplistic representation of GR activity. It is difficult to uncouple the therapeutic and harmful effects mediated by GR, but some useful information that might change the current perspective is appearing in the literature. The generation of gene expression ‘fingerprints’ produced by different GR agonists in target and off-target human tissues could be useful in identifying drug candidates with an improved therapeutic ratio.     

Giant exciton-enhanced shift currents and direct current conduction with subbandgap photo excitations produced by many-electron interactions

Shift current is a direct current generated from nonlinear light–matter interaction in a noncentrosymmetric crystal and is considered a promising candidate for next-generation photovoltaic devices. The mechanism for shift currents in real materials is, however, still not well understood, especially if electron–hole interactions are included. Here, we employ a first-principles interacting Green’s-function approach on the Keldysh contour with real-time propagation to study photocurrents generated by nonlinear optical processes under continuous wave illumination in real materials. We demonstrate a strong direct current shift current at subbandgap excitation frequencies in monolayer GeS due to strongly bound excitons, as well as a giant excitonic enhancement in the shift current coefficients at above bandgap photon frequencies. Our results suggest that atomically thin two-dimensional materials may be promising building blocks for next-generation shift current devices.

When continuous wave light is shone on a noncentrosymmetric crystal, a direct current (DC) can arise due to a second-order optical response of the crystal. The origin of this current is interpreted to be related to the “shift” (1–4) of the intracell coordinates of the excited electron. This so-called shift current is proposed as an alternative to the photocurrent generated by traditional semiconductor p–n junctions (i.e., a junction between hole-doped [p-type] and electron-doped [n-type] semiconductors) for photovoltaic applications (5, 6). Unlike conventional photovoltaic devices, shift current is a bulk phenomenon, which does not require a p–n junction to separate the optically generated electron–hole pair for a DC. Moreover, recent studies reveal that the photocarriers in shift current can have long travel distances, which is distinct from the usual drift transport mechanism in traditional solar cells (7, 8) and makes shift current a promising candidate for efficient energy conversion.Despite many investigations over the past decade, a basic understanding of shift currents is far from complete. Most theoretical studies to date rely on the assumption of having noninteracting particles (3–6, 9–11). Given that it is well known that light-induced electron–hole pairs can form bound or resonant excitons (correlated electron–hole states), which dominate and qualitatively change the absorption features of semiconductors, electron–hole interactions or excitons are expected to play a large role in shift currents, especially for reduced dimensional systems. However, it is not straight forward to generalize existing ab initio methods [such as the ab initio GW plus Bethe-Salpeter equation (GW-BSE) approach (12)], used to understand and compute excitonic effects in linear optical absorption, to study nonlinear optical responses. Different model approaches to investigate the effects of many-electron interactions on nonlinear optical responses of materials have been proposed. For instance, a Floquet-based model Hamiltonian formalism showed that excitonic effects enhance nonlinear response (13). In the specific case of second harmonic generation, first-principles approaches have been developed and applied to real materials, for instance, by making an approximation to the full many-body perturbation theory treatment (14, 15) or to the time-dependent density function theory, in which electron interaction effects are taken into account via simplified kernels (16). A real-time formulation based on propagating the time-dependent Schrodinger equation has also been developed (17) and applied to second harmonic generation (18). For shift currents in real materials, only one recent study considered the effects of excitons on the linear optical coefficient that might influence shift currents, but these authors included only the effects of excitons on the electromagnetic field profile in a bulk sample, and the crucial process of shift current generation itself is still treated within an independent-particle picture (11). Thus, there is still no first-principles calculation and understanding of the role of many-electron interactions, particularly those due to excitons, on shift currents.Here, we show from first principles that 1) bound exciton states in the band gap can generate substantial shift currents, and 2) excitonic effects in the electron–hole continuum part of the spectrum can also greatly enhance shift currents due to the enhancement of the optical matrix elements from the coherence of the electron–hole pairs and to interexciton couplings that arose in the nonlinear responses.     

Efficient radiosynthesis and preclinical evaluation of [18F]FOMPyD as a positron emission tomography tracer candidate for TrkB/C receptor imaging

Herein we report an efficient radiolabeling of a ¹⁸F-fluorinated derivative of dual inhibitor GW2580, with its subsequent evaluation as a positron emission tomography (PET) tracer candidate for imaging of two neuroreceptor targets implicated in the pathophysiology of neurodegeneration: tropomyosin receptor kinases (TrkB/C) and colony stimulating factor receptor (CSF-1R). [¹⁸F]FOMPyD was synthesized from a boronic acid pinacolate precursor via copper-mediated ¹⁸F-fluorination concerted with thermal deprotection of the four Boc groups on a diaminopyrimidine moiety in an 8.7±2.8% radiochemical yield, a radiochemical purity >99%, and an effective molar activity of 187±93 GBq/μmol. [¹⁸F]FOMPyD showed moderate brain permeability in wild-type rats (SUV_max = 0.75) and a slow washout rate. The brain uptake was partially reduced (ΔAUC_40–90 = 11.6%) by administration of the nonradioactive FOMPyD (up to 30 μg/kg). In autoradiography, [¹⁸F]FOMPyD exhibits ubiquitous distribution in rat and human brain tissues with relatively high nonspecific binding revealed by self-blocking experiment. The binding was blocked by TrkB/C inhibitors, but not with a CSF-1R inhibitor, suggesting selective binding to the former receptor. Although an unfavorable pharmacokinetic profile will likely preclude application of [¹⁸F]FOMPyD as a PET tracer for brain imaging, the concomitant one-pot copper-mediated ¹⁸F-fluorination/Boc-deprotection is a practical technique for the automated radiosynthesis of acid-sensitive PET tracers.     

Expression of hGC-1 is correlated with differentiation of gastric carcinoma

AIMS: The human G-CSF-stimulated clone-1 (hGC-1) gene encodes a 510-amino acid olfactomedin-related glycoprotein whose exact in vivo localization and function still remain elusive. The aim of this study was to demonstrate hGC-1 protein localization in the normal human gastrointestinal tract and to explore further a potential relationship between hGC-1 expression and gastric carcinoma. METHODS AND RESULTS: A specific hGC-1 polyclonal antibody raised against purified hGC-1 protein was developed and characterized. Using immunohistochemistry, it was demonstrated that hGC-1 is expressed in the oesophagus, stomach, small intestine and colon. The expression pattern of hGC-1 protein in 173 cases of gastric carcinoma was investigated and a striking correlation was demonstrated between hGC-1 expression and histological type and differentiation of gastric carcinoma. Enhanced hGC-1 expression was more frequently seen in intestinal-type adenocarcinoma, whereas loss of expression tended to occur in the diffuse type. hGC-1 was highly expressed in well or moderately differentiated cancers and was remarkably reduced or lost in poorly differentiated or undifferentiated tumours. CONCLUSIONS: These investigations have defined for the first time the expression pattern of hGC-1 in the normal human gastrointestinal tract and provide a novel and sensitive marker for the differentiation of gastric carcinoma.