Assessing the reduction of viral infectivity in HPV16/18-positive women after one, two, and three doses of Gardasil-9 (RIFT): Study protocol.

Human Papillomavirus (HPV) prophylactic vaccination has proven effective in preventing new infections, but it does not treat existing HPV infections or associated diseases. Hence, there is still an important reservoir of HPV in adults, as vaccination programs are mainly focused on young women. The primary objective of this non-randomized, open-label trial is to evaluate if a 3-dose regimen of Gardasil-9 in HPV16/18-positive women could reduce the infective capacity of their body fluids.

Scaling-Up Microwave-Assisted Synthesis of Highly Defective Pd@UiO-66-NH Catalysts for Selective Olefin Hydrogenation under Ambient Conditions.

The need to develop green and cost-effective industrial catalytic processes has led to growing interest in preparing more robust, efficient, and selective heterogeneous catalysts at a large scale. In this regard, microwave-assisted synthesis is a fast method for fabricating heterogeneous catalysts (including metal oxides, zeolites, metal-organic frameworks, and supported metal nanoparticles) with enhanced catalytic properties, enabling synthesis scale-up. Herein, the synthesis of nanosized UiO-66-NH was optimized via a microwave-assisted hydrothermal method to obtain defective matrices essential for the stabilization of metal nanoparticles, promoting catalytically active sites for hydrogenation reactions (760 kg·m·day space time yield, STY).

SU-101 for the removal of pharmaceutical active compounds by the combination of adsorption/photocatalytic processes.

Pharmaceutical active compounds (PhACs) are some of the most recalcitrant water pollutants causing undesired environmental and human effects. In absence of adapted decontamination technologies, there is an urgent need to develop efficient and sustainable alternatives for water remediation. Metal-organic frameworks (MOFs) have recently emerged as promising candidates for adsorbing contaminants as well as providing photoactive sites, as they possess exceptional porosity and chemical versatility.

Molecular Recognition of Tyrosine-Containing Polypeptides with Pseudopeptidic Cages Unraveled by Fluorescence and NMR Spectroscopies.

The molecular recognition of Tyr-containing peptide copolymers with pseudopeptidic cages has been studied using a combination of fluorescence and NMR spectroscopies. Fluorescence titrations rendered a reasonable estimation of the affinities, despite the presence of dynamic quenching masking the unambiguous detection of the supramolecular complexes. Regarding NMR, the effect of polypeptide (PP) binding on relaxation and diffusion parameters of the cages is much more reliable than the corresponding chemical shift perturbations.

Impact of the Covid-19 pandemic on the management of gynecologic cancer: a Spanish survey. Observational, multicenter study.

Background: The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) pandemic changed the distribution of healthcare resources, leading in many cases to the suspension of all non-essential treatments and procedures and representing a challenge for medical professionals. The objective of this study was to evaluate whether clinical protocols in gynecologic oncology care were modified as a result of the pandemic and to assess surgeons' perceptions regarding the management of gynecologic cancers".

Methods: Data were collected through an anonymous and voluntary survey sent via email to healthcare professionals in the field of gynecologic oncology in Spain.

Enhanced adsorption-catalysis combination for the removal of sulphur from fuels using polyoxometalates supported on amphipathic hybrid mesoporous silica nanoparticles.

Polyoxometalate (POM) mesoporous silica-based materials with a low POM loading have been designed with hydrophilic and hydrophobic properties. These materials act as powerful heterogeneous catalysts in oxidative desulfurization (ODS), owing to their ability to adsorb both HO and sulphur-containing compounds from the model oil simultaneously. The formation of charge transfer salts through ion pair interaction with a choline functionality, available on the hybrid silica support, affords robust and recyclable heterogeneous catalysts for the ODS process under mild conditions (45 min and 40 °C).

Pseudopeptidic host adaptation in peptide recognition unveiled by ion mobility mass spectrometry.

Complexation of the glutamic-tyrosine-glutamic tripeptide (EYE) with a series of pseudopeptidic cages has been thoroughly investigated using different analytical techniques. The stoichiometry and affinities of the supramolecular host : guest complexes both in aqueous solution and in the gas-phase were obtained from a suitable combination of fluorescence spectroscopy, NMR, and mass spectrometry (MS) methods. The cages bearing basic groups (lysine, ornitine and histidine) display the tightest EYE binding in aqueous media following the order CyHis > CyLys > CyOrn, thus suggesting that Tyr side chain encapsulation is additionally modulated by the identity of the cage side chains and their ability to be engaged in polar interactions with the EYE peptide.

Inhibition of Sema-3A Promotes Cell Migration, Axonal Growth, and Retinal Ganglion Cell Survival.

Purpose: Semaphorin 3A (Sema-3A) is a secreted protein that deflects axons from inappropriate regions and induces neuronal cell death. Intravitreal application of polyclonal antibodies against Sema-3A prevents loss of retinal ganglion cells ensuing from axotomy of optic nerves. This suggested a therapeutic approach for neuroprotection via inhibition of the Sema-3A pathway.

Semaphorin 3A-Glycosaminoglycans Interaction as Therapeutic Target for Axonal Regeneration.

Semaphorin 3A (Sema3A) is a cell-secreted protein that participates in the axonal guidance pathways. Sema3A acts as a canonical repulsive axon guidance molecule, inhibiting CNS regenerative axonal growth and propagation. Therefore, interfering with Sema3A signaling is proposed as a therapeutic target for achieving functional recovery after CNS injuries.

Modulation of Src Kinase Activity by Selective Substrate Recognition with Pseudopeptidic Cages.

The selective recognition of tyrosine residues in peptides is an appealing approach to inhibiting their tyrosine kinase (TK)-mediated phosphorylation. Herein, we describe pseudopeptidic cages that efficiently protect substrates from the action of the Src TK enzyme, precluding the corresponding Tyr phosphorylation. Fluorescence emission titrations show that the most efficient cage inhibitors strongly bind the peptide substrates with a very good correlation between the binding constant and the inhibitory potency.

Does living close to a petrochemical complex increase the adverse psychological effects of the COVID-19 lockdown?

The petrochemical industry has made the economic development of many local communities possible, increasing employment opportunities and generating a complex network of closely-related secondary industries. However, it is known that petrochemical industries emit air pollutants, which have been related to different negative effects on mental health. In addition, many people around the world are being exposed to highly stressful situations deriving from the COVID-19 pandemic and the lockdowns adopted by national and regional governments.

Dynamic Stereoselection of Peptide Helicates and Their Selective Labeling of DNA Replication Foci in Cells*.

Although largely overlooked in peptide engineering, coordination chemistry offers a new set of interactions that opens unexplored design opportunities for developing complex molecular structures. In this context, we report new artificial peptide ligands that fold into chiral helicates in the presence of labile metal ions such as Fe and Co . Heterochiral β-turn-promoting sequences encode the stereoselective folding of the peptide ligands and define the physicochemical properties of their corresponding metal complexes.

Importance of structure-based studies for the design of a novel HIV-1 inhibitor peptide.

Based on the structure of an HIV-1 entry inhibitor peptide two stapled- and a retro-enantio peptides have been designed to provide novel prevention interventions against HIV transmission. The three peptides show greater inhibitory potencies in cellular and mucosal tissue pre-clinical models than the parent sequence and the retro-enantio shows a strengthened proteolytic stability. Since HIV-1 fusion inhibitor peptides need to be embedded in the membrane to properly interact with their viral target, the structural features were determined by NMR spectroscopy in micelles and solved by using restrained molecular dynamics calculations.

MCR-ALS analysis of H NMR spectra by segments to study the zebrafish exposure to acrylamide.

Metabolomics is currently an important field within bioanalytical science and NMR has become a key technique for drawing the full metabolic picture. However, the analysis of H NMR spectra of metabolomics samples is often very challenging, as resonances usually overlap in crowded regions, hindering the steps of metabolite profiling and resonance integration. In this context, a pre-processing method for the analysis of 1D H NMR data from metabolomics samples is proposed, consisting of the blind resolution and integration of all resonances of the spectral dataset by multivariate curve resolution-alternating least squares (MCR-ALS).

Live-Cell-Templated Dynamic Combinatorial Chemistry.

Dynamic covalent chemistry combines in a single step the screening and synthesis of ligands for biomolecular recognition. In order to do that, a chemical entity is used as template within a dynamic combinatorial library of interconverting species, so that the stronger binders are amplified due to the efficient interaction with the target. Here we employed whole A549 living cells as template in a dynamic mixture of imines, for which amplification reflects the efficient and selective interaction with the corresponding extracellular matrix.

Targeting redox metabolism: the perfect storm induced by acrylamide poisoning in the brain.

Exposure to acrylamide may lead to different neurotoxic effects in humans and in experimental animals. To gain insights into this poorly understood type of neurotoxicological damage, we used a multi-omic approach to characterize the molecular changes occurring in the zebrafish brain exposed to acrylamide at metabolite, transcript and protein levels. We detected the formation of acrylamide adducts with thiol groups from both metabolites and protein residues, leading to a quasi-complete depletion of glutathione and to the inactivation of different components of the thioredoxin system.

pH-Dependent Chloride Transport by Pseudopeptidic Cages for the Selective Killing of Cancer Cells in Acidic Microenvironments.

Acidic microenvironments in solid tumors are a hallmark of cancer. Inspired by that, we designed a family of pseudopeptidic cage-like anionophores displaying pH-dependent activity. When protonated, they efficiently bind chloride anions.

Peptide Assembly on the Membrane Determines the HIV-1 Inhibitory Activity of Dual-Targeting Fusion Inhibitor Peptides.

Novel strategies in the design of HIV-1 fusion/entry inhibitors are based on the construction of dual-targeting fusion proteins and peptides with synergistic antiviral effects. In this work we describe the design of dual-targeting peptides composed of peptide domains of E2 and E1 envelope proteins from Human Pegivirus with the aim of targeting both the loop region and the fusion peptide domains of HIV-1 gp41. In a previous work, we described the inhibitory role of a highly conserved fragment of the E1 protein (domain 139-156) which interacts with the HIV-1 fusion peptide at the membrane level.

Comparative analysis of H NMR and H-C HSQC NMR metabolomics to understand the effects of medium composition in yeast growth.

In nuclear magnetic resonance (NMR) metabolomics, most of the studies have been focused on the analysis of one-dimensional proton (1D H) NMR, whereas the analysis of other nuclei, such as C, or other NMR experiments are still underrepresented. The preference of 1D H NMR metabolomics lies on the fact that it has good sensitivity and a short acquisition time, but it lacks spectral resolution because it presents a high degree of overlap. In this study, the growth metabolism of yeast ( Saccharomyces cerevisiae) was analyzed by 1D H NMR and by two-dimensional (2D) H-C heteronuclear single quantum coherence (HSQC) NMR spectroscopy, leading to the detection of more than 50 metabolites with both analytical approaches.

Mesoporous SBA-15 modified with titanocene complexes and ionic liquids: interactions with DNA and other molecules of biological interest studied by solid state electrochemical techniques.

The immobilization of two titanocene complexes on SBA-15 has been accomplished following post-synthetic procedures. The ionic liquid, 1-methyl-3-[(triethoxysilyl)propyl]imidazolium chloride, has also been incorporated into the titanium containing materials to determine its influence on the interaction with molecules of biological interest. Cyclic voltammetry has been used to study the influence of the ionic liquid on the mechanism of reduction of titanocene derivatives.

Modulation of the mechanism of apoptosis in cancer cell lines by treatment with silica-based nanostructured materials functionalized with different metallodrugs.

The mesoporous silica-based material SBA-15 (Santa Barbara Amorphous-15) has been modified with the aminodiol ligand 3-[bis(2-hydroxyethyl)amino]propyltriethoxysilane (PADOH) to give the corresponding material SBA-PADOH. Subsequent functionalization with a diorganotin(iv) compound, SnPh2Cl2 (1), and with two titanocene derivatives, TiCp2Cl2 ([Ti(η5-C5H5)2Cl2] (2)) and TiCpCpPhNfCl2 ([Ti(η5-C5H5)(η5-C5H4CHPhNf)Cl2] (3) (Ph = C6H5; Nf = C10H7)), gave the materials SBA-PADO-SnPh2 (M1), SBA-PADO-TiCp2 (M2) and SBA-PADO-TiCpCp* (M3), respectively. SBA-PADOH and M1-M3 have been characterized by various techniques such as FT-IR, XRD, XRF, solid-state NMR, nitrogen adsorption-desorption isotherms, electrochemical methods, SEM and TEM, observing that the functionalization has mainly taken place inside the pores of the corresponding porous system.

Dynamic Covalent Identification of an Efficient Heparin Ligand.

Despite heparin being the most widely used macromolecular drug, the design of small-molecule ligands to modulate its effects has been hampered by the structural properties of this polyanionic polysaccharide. Now a dynamic covalent selection approach is used to identify a new ligand for heparin, assembled from extremely simple building blocks. The amplified molecule strongly binds to heparin (K in the low μm range, ITC) by a combination of electrostatic, hydrogen bonding, and CH-π interactions as shown by NMR and molecular modeling.

Compression of multidimensional NMR spectra allows a faster and more accurate analysis of complex samples.

We propose an approach to efficiently compress and denoise multidimensional NMR spectral data, improving their corresponding storage, handling, and analysis. This method has been tested with 2D homonuclear, 2D and 3D heteronuclear, and 2D phase-sensitive NMR spectral data and shown to be especially powerful for 2D NMR metabolomics studies.

Reversible Self-Assembly of Water-Soluble Gold(I) Complexes.

The reaction of the gold polymers containing bipyridyl and terpyridyl units, [Au(C≡CCHN)] and [Au(C≡CCHN)], with the water-soluble phosphines 1,3,5-triaza-7-phosphatricyclo[3.3.1.