Chromatin remodeling agents for cancer therapy

Alterations in chromatin structure profoundly influence gene expression during normal cellular homeostasis and malignant transformation. Methylation of cytosines within CpG islands located in promoter and proximal coding regions facilitates recruitment of chromatin-remodeling proteins, which inhibits gene expression. Posttranslational modifications, such as acetylation, methylation, and phosphorylation, of core histone proteins \u27\u27mark\u27\u27 regions of chromatin for recognition by multiprotein complexes, which promote either chromatin relaxation and gene expression or chromatin compaction and repression of gene expression. Many genes become transcriptionally silenced during the development of cancer. Covalent epigenetic modifications such as DNA hypermethylation and histone post-translational modifications are an important early event during carcinogenesis and tumor development. Genes involved in key DNA damage responses pathways, apoptosis signaling and DNA repair, can frequently become methylated and epigenetically silenced in tumors. This may lead to differences in intrinsic sensitivity of tumors to chemotherapy, depending on the specific function of the gene inactivated. The fact that cancer can have an epigenetic etiology has encouraged the development of a new therapeutic option that might be termed "epigenetic therapy". The DNA methylation paradox, manifested as derepression of cancer-testis antigens and silencing of tumor suppressors during malignant transformation, provides rationale for the utilization of chromatin remodeling agents for cancer therapy. In this review, the recent advances in the understanding and clinical development of DNA methyltransferase and Histone deacetylase inhibitors, as well as their current role in cancer therapy, will be discussed

Deterministic Thermal Sculpting of Large-Scale 2D Semiconductor Nanocircuits

Two-dimensional (2D) Transition Metal Dichalcogenide semiconductor (TMDs) nanocircuits are deterministically engineered over large-scale substrates. The original approach combines large-area physical growth of 2D TMDs layer with high resolution thermal - Scanning Probe Lithography (t-SPL), to reshape the ultra-thin semiconducting layers at the nanoscale level. We demonstrate the additive nanofabrication of few-layer MoS2 nanostructures, grown in the 2H-semiconducting TMD phase, as shown by their Raman vibrational fingerprints and by their optoelectronic response. The electronic signatures of the MoS2 nanostructures are locally identified by Kelvin probe force microscopy providing chemical and compositional contrast at the nanometer scale. Finally, the potential role of the 2D TMD nanocircuits as building blocks of deterministic 2D semiconducting interconnections is demonstrated by high-resolution local conductivity maps showing the competitive transport properties of these large-area nanolayers. This work thus provides a powerful approach to scalable nanofabrication of 2D nano-interconnects and van der Waals heterostructures, and to their integration in real-world ultra-compact electronic and photonic nanodevices.Comment: 17 pages, 4 figure

Do Animals Play a Role in the Transmission of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)? A Commentary

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the Beta-coronavirus genus. It is 96.2% homologous to bat CoV RaTG13 and 88% homologous to two bat SARS-like coronaviruses. SARS-CoV-2 is the infectious agent responsible for the coronavirus disease (COVID-19), which was first reported in the Hubei province of Wuhan, China, at the beginning of December 2019. Human transmission from COVID-19 patients or incubation carriers occurs via coughing, sneezing, speaking, discharge from the nose, or fecal contamination. Various strains of the virus have been reported around the world, with different virulence and behavior. In addition, SARS-CoV-2 shares certain epitopes with some taxonomically related viruses, with tropism for the most common synanthropic animals. By elucidating the immunological properties of the circulating SARS-CoV-2, a partial protection due to human–animal interactions could be supposed in some situations. In addition, differential epitopes could be used for the differential diagnosis of SARS-CoV-2 infection. There have been cases of transmission from people with COVID-19 to pets such as cats and dogs. In addition, wild felines were infected. All These animals were either asymptomatic or mildly symptomatic and recovered spontaneously. Experimental studies showed cats and ferrets to be more susceptible to COVID-19. COVID-19 positive dogs and felines do not transmit the infection to humans. In contrast, minks at farms were severely infected from people with COVID-19. A SARS-Cov-2 variant in the Danish farmed mink that had been previously infected by COVID-19 positive workers, spread to mink workers causing the first case of animal-to-human infection transmission that causes a moderate decreased sensitivity to neutralizing antibodies. Thus, more investigations are necessary. It remains important to understand the risk that people with COVID-19 pose to their pets, as well as wild or farm animals so effective recommendations and risk management measures against COVID-19 can be made. A One Health unit that facilitates collaboration between public health and veterinary services is recommended

Controlling resonant surface modes by arbitrary light induced optical anisotropies

In this work the sensitivity of Bloch Surface Waves to laser-induced anisotropy of azo-polymeric thin layers is expe rimentally shown . The nanoscale reshaping of the films via thermal-Scanning Probe Lithography allows to couple light to circular photonic nanocavities, tailoring on-demand resonant BSW confined within the nanocavity

Duration of untreated illness and depression severity are associated with cognitive impairment in mood disorders

Introduction: In this study we estimated the rate and the trajectory of cognitive impairment in a naturalistic sample of outpatients with major depressive disorder (MDD) and bipolar disorder (BD) and its correlation with different variables. Materials and methods: An overall sample of 109 outpatients with MDD or BD was assessed for multiple clinical variables, including duration of untreated illness (DUI), and tested using the Montreal Cognitive Assessment (MoCA) during Major Depressive Episodes (MDE) and after remission. Correlations between MoCA scores and the clinical variables were then computed. Results: About 50% of patients with MDD and BD showed mild cognitive impairment during MDE. Improvement of cognitive function between depression and remission was significant, even though residual symptoms were observed especially in the most impaired patients. Of note, cognitive performance during depression was negatively associated with depression severity and DUI. Discussion: Present findings confirm available evidence about patterns of cognitive impairment in mood disorders, in terms of prevalence and persistence beyond remission in most severe cases. Moreover, a longer DUI was associated with worse cognitive performance during depression, and consequently with poorer outcome, underlining the importance of prompt treatment of these disorders also in light of a cognitive perspective. Keywords: bipolar disorder, cognitive dysfunction, duration of untreated illness, major depressive disorder, Montreal cognitive assessmen

Self-Organized Tailoring of Faceted Glass Nanowrinkles for Organic Nanoelectronics

Self-organized wrinkled templates are homogeneously fabricated over a large area (cm2) glass substrates by defocused ion beam irradiation, demonstrating the capability to induce and modify at will the out-of-plane tilt of the nanofacets with selected slope. We identify a region of morphological instability which leads to faceting for incidence angles of the ion beam with respect to the surface, \u3b8, in the range 15\ub0 64 \u3b8 64 45\ub0, while for normal incidence, \u3b8 = 0\ub0, and for grazing incidence at about 55\u201360\ub0 a flat morphology is achieved. The crucial parameter which controls the slope of the sawtooth profile is the local ion beam incidence angle on the facets which corresponds to the maximum erosion velocity. For \u3b8 = 30\ub0, improved lateral order of the templates is found which can be exploited for the anisotropic confinement of functional layers. Here, we highlight the crucial role of the 1D nanopatterned template in driving the anisotropic crystallization of spun-cast conductive polymer thin films in registry with the faceted nanogrooves. In response, anisotropic electrical transport properties of the nanopatterned film are achieved with overall improvement higher than 60% with respect to a flat reference, thus showing the potential of such transparent large-area templates in nanoelectronics, optoelectronics, and biosensing

Free-standing plasmonic nanoarrays for leaky optical waveguiding and sensing

Flat optics nanogratings supported on thin free-standing membranes offer the opportunity to combine narrowband waveguided modes and Rayleigh anomalies for sensitive and tunable biosensing. At the surface of high-refractive index Si3N4 membranes we engineered lithographic nanogratings based on plasmonic nanostripes, demonstrating the excitation of sharp waveguided modes and lattice resonances. We achieved fine tuning of these optical modes over a broadband Visible and Near-Infrared spectrum, in full agreement with numerical calculations. This possibility allowed us to select sharp waveguided modes supporting strong near-field amplification, extending for hundreds of nanometres out of the grating and enabling versatile biosensing applications. We demonstrate the potential of this flat-optics platform by devising a proof-of-concept nanofluidic refractive index sensor exploiting the long-range waveguided mode operating at the sub-picoliter scale. This free-standing device configuration, that could be further engineered at the nanoscale, highlights the strong potential of flat-optics nanoarrays in optofluidics and nanofluidic biosensing. (C) 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreemen

Nutrition and Physical Activity in CKD patients

Chronic kidney disease (CKD) patients are at risk for protein-energy wasting, abnormal body composition and impaired physical capacity. These complications lead to increased risk of hospitalization, morbidity and mortality.In CKD patient as well as in healthy people, there is a close association between nutrition and physical activity. Namely, inadequate nutrient (energy) intake impairs physical performance thus favoring a sedentary lifestyle: this further contributes to loss of muscle strength and mass, which limit the quality of life and rehabilitation of CKD patients. In CKD as well as in end-stage-renal-disease patients, regular physical activity coupled with adequate energy and protein intake counteracts protein-energy wasting and related comorbidity and mortality. In summary, exercise training can positively influence nutritional status and the perception of well-being of CKD patients and may facilitate the anabolic effects of nutritional interventions