Interplay of Modified Sialic Acid Inhibitors and the Human Parainfluenza Virus 1 Hemagglutinin-Neuraminidase Active Site.

In the search for effective antivirals against Paramyxoviridae, the dynamics of human parainfluenza virus type 1 hemagglutinin-neuraminidase (hPIV1-HN) inhibition offers a promising perspective. This study focuses on the potential of C5- and C4-modified 2,3-unsaturated sialic acid (DANA) inhibitors and highlights their interaction with the hPIV1-HN enzyme. We show that a strategic substitution, replacing the C5 isopropyl group in BCX 2798 with a trifluoroacetyl function, increases inhibitory potency 3- to 4-fold.

Design of Wideband High-Gain Patch Antenna Array for High-Temperature Applications.

A low-profile, wideband, and high-gain antenna array, based on a novel double-H-shaped slot microstrip patch radiating element and robust against high temperature variations, is proposed in this work. The antenna element was designed to operate in the frequency range between 12 GHz and 18.25 GHz, with a 41.

Analysis of the intramolecular 1,7-lactone of N-acetylneuraminic acid using HPLC-MS: relationship between detection and stability.

A subclass of the sialic acid family consists of intramolecular lactones that may function as key indicators of physiological and pathological states. However, the existence of these compounds in free form is highly improbable, since they are unlikely to exist in an aqueous solution due to their lability. Current analytical method used to detect them in biological fluids has not recognized their reactivity in solution and is prone to misidentification.

Design, Synthesis, and Antiviral Evaluation of Sialic Acid Derivatives as Inhibitors of Newcastle Disease Virus Hemagglutinin-Neuraminidase: A Translational Study on Human Parainfluenza Viruses.

Global infections with viruses belonging to the , such as Newcastle disease virus (NDV) or human parainfluenza viruses (hPIVs), pose a serious threat to animal and human health. NDV-HN and hPIVs-HN (HN hemagglutinin-neuraminidase) share a high degree of similarity in catalytic site structures; therefore, the development of an efficient experimental NDV host model (chicken) may be informative for evaluating the efficacy of hPIVs-HN inhibitors. As part of the broad research in pursuit of this goal and as an extension of our published work on antiviral drug development, we report here the biological results obtained with some newly synthesized C4- and C5-substituted 2,3-unsaturated sialic acid derivatives against NDV.

Surrogate-Model-Based Interval Analysis of Spherical Conformal Array Antenna with Power Pattern Tolerance.

A method based on an interval arithmetic is proposed to analyze uncertain factors such as the curvature radii, excitation amplitude, and excitation phase of a spherical conformal array antenna. An interval description of element factors under different curvature radii of spherical substrates is established using the surrogate model based on the data obtained through a full-wave analysis method. The interval formula of the spherical curvature radius and array element position error is derived and the effects of the spherical radius tolerance, excitation amplitude tolerance, and excitation phase tolerance on the antenna power pattern are studied.

Hexahydrocannabinol on the Light Cannabis Market: The Latest "New" Entry.

Hexahydrocannabinols (HHCs), referred to as (9)-HHC and (9)-HHC diastereoisomers, are poorly studied cannabinoids naturally found in small concentrations in the pollen and the seeds of the hemp plants. In this study, for the first time, we describe the finding of (9)-HHC and (9)-HHC in two commercialized hemp derived products. The achievement of reference standards by semisynthetic or isolation approach allows us to develop and validate a gas chromatography mass spectrometry method for the identification and quantification of HHCs in hemp-derived resin.

"Conical" Frustum Multi-Beam Phased Arrays for Air Traffic Control Radars.

The design of conical frustum phased array antennas for air traffic control (ATC) radar systems is addressed. The array architecture, which is controlled by a fully digital beam-forming (DBF) network, is composed by a set of equal vertical modules. Each module consists of a linear sparse array that generates on receive multiple instantaneous beams pointing along different directions in elevation.

Small-Molecules as Chemiluminescent Probes to Detect Lipase Activity.

The set-up of highly sensitive detection tools to evaluate lipase activity remains a central goal in different fields. In this context, we proposed new chemiluminescent 1,2-dioxetane luminophores, sharing an octanoyl triggerable group, to monitor lipase activity. We herein report the synthesis and both the evaluation of their luminescence emission profile and their enzyme-substrate specificity, generated by three different commercial lipases (, , and ) and one esterase (porcine liver esterase, PLE, as a literature control).

Human Sarcopenic Myoblasts Can Be Rescued by Pharmacological Reactivation of HIF-1α.

Sarcopenia, an age-related decline in muscle mass and strength, is associated with metabolic disease and increased risk of cardiovascular morbidity and mortality. It is associated with decreased tissue vascularization and muscle atrophy. In this work, we investigated the role of the hypoxia inducible factor HIF-1α in sarcopenia.

Neu3 Sialidase Activates the RISK Cardioprotective Signaling Pathway during Ischemia and Reperfusion Injury (IRI).

Coronary reperfusion strategies are life-saving approaches to restore blood flow to cardiac tissue after acute myocardial infarction (AMI). However, the sudden restoration of normal blood flow leads to ischemia and reperfusion injury (IRI), which results in cardiomyoblast death, irreversible tissue degeneration, and heart failure. The molecular mechanism of IRI is not fully understood, and there are no effective cardioprotective strategies to prevent it.

Low Discrepancy Sparse Phased Array Antennas.

Sparse arrays have grating lobes in the far field pattern due to the large spacing of elements residing in a rectangular or triangular grid. Random element spacing removes the grating lobes but produces large variations in element density across the aperture. In fact, some areas are so dense that the elements overlap.

Triple-Band Single-Layer Rectenna for Outdoor RF Energy Harvesting Applications.

A triple-band single-layer rectenna for outdoor RF energy applications is introduced in this paper. The proposed rectenna operates in the frequency bands of LoRa, GSM-1800, and UMTS-2100 networks. To obtain a triple-band operation, a modified E-shaped patch antenna is used.

Multiple Solutions Starting from Real Shaped Beams in Equispaced Linear Arrays.

In the present work, the theoretical basis of the multiplicity of solutions obtained from an initial real symmetric distribution is derived. This initial solution is devoted to generating an equivalent pure real shaped-beam pattern for a concrete synthesis scenario. However, these new solutions are not based on real symmetric distributions; hence, not based on the generation of pure real patterns.

Intramolecular Lactones of Sialic Acids.

The so-called "" has become an attractive research area, as an increasing number of natural products containing a sialic acid moiety have been shown to play important roles in biological, pathological, and immunological processes. The intramolecular lactones of sialic acids are a subclass from this crucial family that could have central functions in the discrimination of physiological and pathological conditions. In this review, we report an in-depth analysis of the synthetic achievements in the preparation of the intramolecular lactones of sialic acids (1,4-, 1,7- and γ-lactones), in their free and/or protected form.

2β-3,4-Unsaturated sialic acid derivatives: Synthesis optimization, and biological evaluation as Newcastle disease virus hemagglutinin-neuraminidase inhibitors.

The optimization of the synthetic protocol to obtain the 3,4-unsaturated sialic acid derivatives, through the fine-tuning of both the Ferrier glycosylation conditions and the subsequent hydrolysis work-up, is herein reported. The accomplishment of the desired β-anomers and some selected α-ones, in pure form, led us to evaluate their specific inhibitory activity towards NDV-HN and human sialidase NEU3. Importantly, the resulting data allowed the identification, for the first time, of three active 3,4-unsaturated sialic acid analogs, showing IC values against NDV-HN in the micromolar range.

Landscape of transcriptome variations uncovering known and novel driver events in colorectal carcinoma.

We focused on an integrated view of genomic changes in Colorectal cancer (CRC) and distant normal colon tissue (NTC) to test the effectiveness of expression profiling on identification of molecular targets. We performed transcriptome on 16 primary coupled CRC and NTC tissues. We identified pathways and networks related to pathophysiology of CRC and selected potential therapeutic targets.

The acidic hydrolysis of -acetylneuraminic 4,5-oxazoline allows a direct functionalization of the C5 position of Neu5Ac2en (DANA).

The acidic hydrolysis of -acetylneuraminic 4,5-oxazoline affords the corresponding 2,3-unsaturated amino ester, which was not previously detected (nor isolated) due to the unexpected rearrangement into its corresponding alcohol. In this work, we unveiled the mechanism of these reactions and optimized the conditions to obtain either synthetic intermediate.

Integrated Analysis of miRNA and mRNA Endorses a Twenty miRNAs Signature for Colorectal Carcinoma.

Colorectal cancer (CRC) ranks as the most frequent carcinoma worldwide. CRC patients show strong prognostic differences and responses to treatment, and 20% have incurable metastatic disease at diagnosis. We considered it essential to investigate mechanisms that control cellular regulatory networks, such as the miRNA-mRNA interaction, known to be involved in cancer pathogenesis.

Lactonization Method To Assign the Anomeric Configuration of the 3,4-Unsaturated Congeners of N-Acetylneuraminic Acid.

Assigning the correct configuration at C2 in sialosides is a standing problem because of the absence of an anomeric hydrogen. All different empirical rules that have been proposed over the years lack general applicability. In particular, the correct configuration of several 3,4-unsaturated derivatives of N-acetylneuraminic acid (Neu5Ac), which have been recently shown to be novel sialidase/neuraminidase inhibitors, could only be tentatively assigned by similarity with the reported 3,4-unsaturated 2O-methyl sialosides.

Clinical and pathological factors influencing survival in a large cohort of triple-negative breast cancer patients.

Background: To provide further information on the clinical and pathological prognostic factors in triple-negative breast cancer (TNBC), for which limited and inconsistent data are available.

Methods: Pathological characteristics and clinical records of 841 TNBCs diagnosed between 1994 and 2015 in four major oncologic centers from Sardinia, Italy, were reviewed. Multivariate hazard ratios (HRs) for mortality and recurrence according to various clinicopathological factors were estimated using Cox proportional hazards models.

Potent Inhibitors against Newcastle Disease Virus Hemagglutinin-Neuraminidase.

Neuraminidase activity is essential for the infection and propagation of paramyxoviruses, including human parainfluenza viruses (hPIVs) and the Newcastle disease virus (NDV). Thus, many inhibitors have been developed based on the 2-deoxy-2,3-didehydro-d-N-acetylneuraminic acid inhibitor (DANA) backbone. Along this line, herein we report a series of neuraminidase inhibitors, having C4 (p-toluenesulfonamido and azido substituents) and C5 (N-perfluorinated chains) modifications to the DANA backbone, resulting in compounds with 5- to 15-fold greater potency than the currently most active compound, the N-trifluoroacetyl derivative of DANA (FANA), toward the NDV hemagglutinin-neuraminidase (NDV-HN).

Power Pattern Sensitivity to Calibration Errors and Mutual Coupling in Linear Arrays through Circular Interval Arithmetics.

The sensitivity to both calibration errors and mutual coupling effects of the power pattern radiated by a linear array is addressed. Starting from the knowledge of the nominal excitations of the array elements and the maximum uncertainty on their amplitudes, the bounds of the pattern deviations from the ideal one are analytically derived by exploiting the Circular Interval Analysis (CIA). A set of representative numerical results is reported and discussed to assess the effectiveness and the reliability of the proposed approach also in comparison with state-of-the-art methods and full-wave simulations.

[Preliminary study on the expression of Toll-like receptors 7 and 8 in bladder urothelial tumors].

The aim of the study was to demonstrate the expression of Toll-like receptor (TLR)-8 and to confirm the expression of TLR-7 on bladder transitional cell carcinomas (TCCs) analyzing the changes in expression between low-grade (LG) and high-grade (HG) and between non-muscle invasive (NMIBC) and muscle-invasive (MIBC) bladder cancers. In our study, 25 patients who underwent transurethral resection (TURB) for bladder TCC have been selected. Thirteen of those had an LG form,while the other cases were classified as HG; the lesions were NMIBC in 18 patients and MIBC in the others seven.