276 research outputs found

    Gold-Catalyzed Cascade Reactions of 4H-Furo[3,2-b]indoles with Allenamides: Synthesis of Indolin-3-one Derivatives

    Get PDF
    Merging the ability of cationic gold(I) catalysts to activate unsaturated \u3c0-systems with the electrophiles driven ring-opening reactions of furans, we describe a new approach to 2-spiroindolin-3-ones from 4H-furo[3,2-b]indoles. The reaction occurs through a cascade sequence involving addition of a gold-activated allene to the furan moiety of the starting furoindole followed by a ring-opening/ring-closing event affording 2-spirocyclopentane-1,2-dihydro-3H-indolin-3-ones in moderate to good yields

    Bilateral peripheral facial palsy and mastoid infiltration as symptoms of relapsed acute myeloid leukemia

    Get PDF
    AbstractBackgroundAlthough Bell's palsy (BP) is the most common cause of peripheral facial palsy (PFP), other etiologies merit investigation.Case reportA 60-year-old female patient presented with recurrent bilateral PFP. Although the patient had a history of acute myeloid leukemia (AML), she had initially been diagnosed with BP-related PFP and had been treated accordingly. When the PFP recurred, additional diagnostic tests were performed. The resulting immunohistochemical profile included CD3 positivity in a few reactive T lymphocytes; positivity for myeloperoxidase in atypical cells; and focal positivity for CD34 and proto-oncogene c-kit proteins in neoplastic cells, thus confirming the suspicion of mastoid infiltration caused by relapsed AML.ConclusionIn patients with neoplastic disease, a finding of PFP calls for extensive investigation in order to rule out the involvement of the temporal bone

    [Ag(PcL)]-Catalysed Domino Approach to 6-Substituted Benzoxazino Isoquinolines

    Get PDF
    In this paper, we describe a new silver catalysed domino approach to 6-substituted benzoxazino isoquinolines starting from 2-alkynylbenzaldehydes and 1-substituted-(2-aminophenyl)methanols. The strategy is characterized by good reaction yields, and can be performed at room temperature as well as under heating (conventional or dielectric) in different reaction times. Best results have been obtained by using silver complexes of macrocyclic pyridine-containing ligands (PcL) as catalysts. The stereoselectivity of the transformation has been investigated by using chiral reaction partners and chiral catalyst, but unfortunately, modest stereoselectivities has been achieved. On the other hand, this approach represents an alternative synthetic strategy for the preparation of 6-substituted benzoxazino isoquinolines, which are the key scaffold of some compounds endowed of biological activity

    Extending the coherence time of spin defects in hBN enables advanced qubit control and quantum sensing

    Full text link
    Spin defects in hexagonal Boron Nitride (hBN) attract increasing interest for quantum technology since they represent optically-addressable qubits in a van der Waals material. In particular, negatively-charged boron vacancy centers (VB−{V_B}^-) in hBN have shown promise as sensors of temperature, pressure, and static magnetic fields. However, the short spin coherence time of this defect currently limits its scope for quantum technology. Here, we apply dynamical decoupling techniques to suppress magnetic noise and extend the spin coherence time by nearly two orders of magnitude, approaching the fundamental T1T_1 relaxation limit. Based on this improvement, we demonstrate advanced spin control and a set of quantum sensing protocols to detect electromagnetic signals in the MHz range with sub-Hz resolution. This work lays the foundation for nanoscale sensing using spin defects in an exfoliable material and opens a promising path to quantum sensors and quantum networks integrated into ultra-thin structures

    Utility of neutrophil-to-lymphocyte ratio to identify long-term survivors among HCC patients treated with sorafenib

    Get PDF
    Sorafenib is the first multikinase inhibitor demonstrating a survival benefit for patients suffering from advanced hepatocellular carcinoma (HCC). However, 1 issue remains open: what is the factor able to predict which patients will be long survivors?In the present study, we harnessed the potential of conditional survival, aiming at estimating the probability that a patient receiving sorafenib survives for more than 3 years.The present multicentric study was conducted on a cohort of 438 HCC patients. The primary end point was conditional overall survival. Kaplan-Meier survival analysis was used to calculate conditional overall survival probabilities at 3 years.The 3-year conditional survival of patients without disease progression highlights that NLR and ECOG are the factors that most accurately predict the probability of long survival. The 3-year conditional survival of patients with disease progression showed a medium effect size for HCV status, alpha-fetoprotein and NLR at all time-points. Macro-vascular portal vein invasion, extra hepatic disease, and BCLC we have a large effect size at 6 months and a medium effect size at 12 and 24 months.Our findings support the use of baseline NLR for the identification of patients with a higher probability of long-survival. NLR should be used as a stratification factor in the forthcoming clinical trials on the drugs for the advanced HCC now in pipeline

    The Encapsulation of Citicoline within Solid Lipid Nanoparticles Enhances Its Capability to Counteract the 6-Hydroxydopamine-Induced Cytotoxicity in Human Neuroblastoma SH-SY5Y Cells

    Get PDF
    (1) Backgrond: Considering the positive effects of citicoline (CIT) in the management of some neurodegenerative diseases, the aim of this work was to develop CIT-Loaded Solid Lipid Nanoparticles (CIT-SLNs) for enhancing the therapeutic use of CIT in parkinsonian syndrome; (2) Methods: CIT-SLNs were prepared by the melt homogenization method using the self-emulsifying lipid GelucireÂź 50/13 as lipid matrix. Solid-state features on CIT-SLNs were obtained with FT-IR, thermal analysis (DSC) and X-ray powder diffraction (XRPD) studies. (3) Results: CIT-SLNs showed a mean diameter of 201 nm, −2.20 mV as zeta potential and a high percentage of entrapped CIT. DSC and XRPD analyses evidenced a greater amorphous state of CIT in CIT-SLNs. On confocal microscopy, fluorescent SLNs replacing unlabeled CIT-SLNs released the dye selectively in the cytoplasm. Biological evaluation showed that pre-treatment of SH-SY5Y dopaminergic cells with CIT-SLNs (50 ”M) before the addition of 40 ”M 6-hydroxydopamine (6-OHDA) to mimic Parkinson’s disease’s degenerative pathways counteracts the cytotoxic effects induced by the neurotoxin, increasing cell viability with the consistent maintenance of both nuclear and cell morphology. In contrast, pre-treatment with CIT 50 and 60 ”M or plain SLNs for 2 h followed by 6-OHDA (40 ”M) did not significantly influence cell viability. (4) Conclusions: These data suggest an enhanced protection exerted by CIT-SLNs with respect to free CIT and prompt further investigation of possible molecular mechanisms that underlie this difference

    Definition of the Prognostic Role of MGMT Promoter Methylation Value by Pyrosequencing in Newly Diagnosed IDH Wild‐Type Glioblastoma Patients Treated with Radiochemotherapy: A Large Multicenter Study

    Get PDF
    Background. O6‐methylguanine (O6‐MeG)‐DNA methyltransferase (MGMT) methylation status is a predictive factor for alkylating treatment efficacy in glioblastoma patients, but its prognostic role is still unclear. We performed a large, multicenter study to evaluate the association between MGMT methylation value and survival. Methods. We evaluated glioblastoma patients with an assessment of MGMT methylation status by pyrosequencing from nine Italian centers. The inclusion criteria were histological diagnosis of IDH wild‐type glioblastoma, Eastern Cooperative Oncology Group Performance Status (ECOG‐PS) ≀2, and radio‐chemotherapy treatment with temozolomide. The relationship between OS and MGMT was investigated with a time‐dependent Receiver Operating Characteristics (ROC) curve and Cox regression models. Results. In total, 591 newly diagnosed glioblastoma patients were analyzed. The median OS was 16.2 months. The ROC analysis suggested a cut‐off of 15% for MGMT methylation. The 2‐year Overall Survival (OS) was 18.3% and 51.8% for MGMT methylation <15% and ≄15% (p < 0.0001). In the multivariable analysis, MGMT methylation <15% was associated with impaired survival (p <0.00001). However, we also found a non‐linear association between MGMT methylation and OS (p = 0.002): median OS was 14.8 months for MGMT in 0–4%, 18.9 months for MGMT in 4–40%, and 29.9 months for MGMT in 40– 100%. Conclusions. Our findings suggested a non‐linear relationship between OS and MGMT promoter methylation, which implies a varying magnitude of prognostic effect across values of MGMT promoter methylation by pyrosequencing in newly diagnosed IDH wild‐type glioblastoma patients treated with chemoradiotherapy

    Caratterizzazione di Batteri Vibrio harveyi irradiati con luce UV e raggi X

    Get PDF
    Lo studio dei batteri sottoposti a stimolazioni dovute all'ambiente Ăš di estremo interesse per impli-cazioni strutturali, meccanicistiche ed evolutive. Bat-teri luminescenti evoluti in determinati ambienti han-no sviluppato particolari risposte e il loro comporta-mento puĂČ fornire informazioni sulla funzione e sulla produzione dell‟enzima luciferina. Per esaminare l'in-terazione con radiazione UV, in condizioni controlla-te di laboratorio sono stati utilizzati ceppi batterici foto-luminescenti appartenenti alla specie Vibrio har-veyi campionati da una grotta costiera con elevato contenuto di radon che genera radiazioni ionizzanti. La sopravvivenza dei ceppi batterici Ăš stata analizza-ta, alla luce e al buio, a seguito di una varietĂ  di trat-tamenti genotossici tra cui esposizione alle radiazioni UV. I ceppi sono stati irradiati mediante una lampada germicida. I risultati hanno dimostrato che la maggior parte dei ceppi esibiscono un basso tasso di sopravvi-venza dopo l'esposizione ai raggi UV. Tutti i ceppi dopo esposizione a luce visibile e ai raggi UV hanno mostrato una forte capacitĂ  di fotoriattivazione. Que-sta capacitĂ  era inaspettata, poichĂ© questi batteri sono stati prelevati da un ambiente buio in assenza raggi UV. Questo porta ad ipotizzare che la fotoriattivazio-ne in questi batteri potrebbe essere stata sviluppata dagli stessi per riparare le lesioni del DNA provocate anche da radiazioni diverse dall‟UV (ad esempio, raggi X) e che i batteri luminescenti potrebbero usare la luce da essi emessa per effettuare la fotoriattivazio-ne. L'elevata capacitĂ  di fotoriattivazione dei batteri Ăš stata anche confermata dai risultati di deconvoluzio-ne. La deconvoluzione Ăš stata applicata agli spettri di emissione che ha evidenziato la presenza di diversi picchi. La presenza del picco nel visibile Ăš in grado di controllare l'enzima fotoliasi
    • 

    corecore