Does vegetation accelerate coastal dune erosion during extreme events?

A broadly accepted paradigm is that vegetation reduces coastal dune erosion. However, we show that during an extreme storm event, vegetation surprisingly accelerates erosion. In 104-m-long beach-dune profile experiments conducted within a flume, we discovered that while vegetation initially creates a physical barrier to wave energy, it also (i) decreases wave run-up, which creates discontinuities in erosion and accretion patterns across the dune slope, (ii) increases water penetration into the sediment bed, which induces its fluidization and destabilization, and (iii) reflects wave energy, accelerating scarp formation.

Design and Synthesis of Novel Raman Reporters for Bioorthogonal SERS Nanoprobes Engineering.

Surface-enhanced Raman spectroscopy (SERS) exploiting Raman reporter-labeled nanoparticles (RR@NPs) represents a powerful tool for the improvement of optical bio-assays due to RRs’ narrow peaks, SERS high sensitivity, and potential for multiplexing. In the present work, starting from low-cost and highly available raw materials such as cysteamine and substituted benzoic acids, novel bioorthogonal RRs, characterized by strong signal (103 counts with FWHM < 15 cm−1) in the biological Raman-silent region (>2000 cm−1), RRs are synthesized by implementing a versatile, modular, and straightforward method with high yields and requiring three steps lasting 18 h, thus overcoming the limitations of current reported procedures. The resulting RRs’ chemical structure has SH-pendant groups exploited for covalent conjugation to high anisotropic gold-NPs.

Design, synthesis and evaluation of RGD peptidomimetic - Gold nanostar conjugates as M21 cell adhesion inhibitors.

Effective targeting of αβ integrin is of high relevance in cancer research as this protein is overexpressed on several types of tumor cells, making such receptor ideal for the development of therapeutics and of diagnostic imaging agents. In this paper, the synthesis of a novel functionalized triazole-based RGD peptidomimetic and its covalent conjugation on pegylated gold nanostars is reported. These highly stable nanoconstructs showed a multivalent effect in binding αβ integrin receptors and proved to inhibit M21 cell adhesion at 25 pM concentration.

Multitargeting application of proline-derived peptidomimetics addressing cancer-related human matrix metalloproteinase 9 and carbonic anhydrase II.

A series of d-proline peptidomimetics were evaluated as dual inhibitors of both human carbonic anhydrases (hCAs) and human gelatinases (MMP2 and MMP9), as these enzymes are both involved in the carcinogenesis and tumor invasion processes. The synthesis and enzyme inhibition kinetics of d-proline derivatives containing a biphenyl sulfonamido moiety revealed an interesting inhibition profile of compound XIV towards MMP9 and CAII. The SAR analysis and docking studies revealed a stringent requirement of a trans geometry for the two arylsulfonyl moieties, which are both necessary for inhibition of MMP9 and CAII.

Adverse drug reactions in SARS-CoV-2 hospitalised patients: a case-series with a focus on drug-drug interactions.

Due to the need of early and emergency effective treatments for COVID-19, less attention may have been paid to their safety during the global emergency. In addition, characteristics of drug-drug interaction (DDI)-related adverse drug reactions (ADRs) in COVID-19 patients have not yet been studied in depth. The aim of the present case-series study is to describe clinical and pharmacological characteristics of SARS-CoV-2 hospitalised patients, focusing on ADRs, particularly those related to DDIs.

Synthesis of morpholine derivatives using the Castagnoli-Cushman reaction as BACE1 inhibitors: Unexpected binding activity of cyclic thioamides.

The Castagnoli-Cushman reaction between diglycolic anhydride and imines was applied for the synthesis of morpholine derivatives containing a thioamide or an amidino group. Enzyme inhibition assays towards BACE1 revealed an unexpected role of the cyclic thioamide group in providing inhibition in the micromolar range. Molecular docking calculations showed the thioamido group interacting with catalytic aspartic acid, and calculated BBB permeability indicated this molecular scaffold as a promising hit for further optimization.

Combination of multicomponent KA and Pauson-Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones.

The Cu-catalyzed multicomponent ketone-amine-alkyne (KA) reaction was combined with a Pauson-Khand cycloaddition to give access of unprecedented constrained spirocyclic pyrrolocyclopentenone derivatives following a DOS couple-pair approach. The polyfunctional molecular scaffolds were tested on the cyclopentenone reactivity to further expand the skeletal diversity, demonstrating the utility of this combined approach in generating novel spiro compounds as starting material for the generation of chemical libraries. The chemoinformatics characterization of the newly-synthesized molecules gave evidence about structural and physicochemical properties with respect to a set of blockbuster drugs, and showed that such scaffolds are drug-like but more spherical and three-dimensional in character than the drugs.

Identification of highly potent and selective MMP2 inhibitors addressing the S1' subsite with d-proline-based compounds.

MMP2 and MMP9, also called gelatinases, play a primary role in the angiogenic switch, as a fundamental step of tumor progression, and show high degree of structural similarity. Clinically successful gelatinase inhibitors need to be highly selective as opposite effects have been found for the two enzymes, and the S1' subsite is the major driver to attain selective and potent inhibitors. The synthesis of d-proline-derived hydroxamic acids containing diverse appendages at the amino group, varying in length and decoration allowed to give insight on the MMP2/MMP9 selectivity around the S1' subsite, resulting in the identification of sub-nanomolar compounds with high selectivity up to 730.

Lenograstim and filgrastim in the febrile neutropenia prophylaxis of hospitalized patients: efficacy and cost of the prophylaxis in a retrospective survey.

Purpose: We conducted a retrospective study to evaluate the efficacy and related costs of using two different molecules of granulocyte-colony stimulating factor (G-CSF) (lenograstim - LENO or filgrastim - FIL) as primary prophylaxis of chemotherapy-induced neutropenia in a hematological inpatient setting.

Methods: The primary endpoints of the analysis were the efficacy of the two G-CSFs in terms of the level of white blood cells, hemoglobin and platelets at the end of the treatment and the per capita direct medical costs related to G-CSF prophylaxis.

Results: Two hundred twelve patients (96 LENO, 116 FIL) have been evaluated.

Diversity-Oriented Synthesis and Chemoinformatic Analysis of the Molecular Diversity of sp-Rich Morpholine Peptidomimetics.

Diversity-Oriented Synthesis (DOS) consists of generating structurally diverse compounds from a complexity-generating reaction followed by cyclization steps and appendage diversity. DOS has gathered interest to systematically explore the chemical space by generating high-quality small-molecule collections as probes to investigate biological pathways. The generation of heterocycles using amino acid and sugar derivatives as building blocks is a powerful approach to access chemical and geometrical diversity thanks to the high number of stereocenters and the polyfunctionality of such compounds.

Design and synthesis of bicyclic acetals as Beta Secretase (BACE1) inhibitors.

Taking advantage of the structural similarity between aspartic proteases, small-molecule peptidomimetic inhibitors that already showed activity towards Secreted Aspartic Protease 2 as anti-Candida agents and HIV protease inhibitors were exploited as potential BACE1 inhibitors. A focused library of 6,8-dioxa-3-azabicyclo[3.2.

Investigation of hollow cylindrical metal terahertz waveguides suitable for cryogenic environments.

The field of terahertz (THz) waveguides continues to grow rapidly, with many being tailored to suit the specific demands of a particular final application. Here, we explore waveguides capable of enabling efficient and accurate power delivery within cryogenic environments (< 4 K). The performance of extruded hollow cylindrical metal waveguides made of un-annealed and annealed copper, as well as stainless steel, have been investigated for bore diameters between 1.

Identification of Novel Human Breast Carcinoma (MDA-MB-231) Cell Growth Modulators from a Carbohydrate-Based Diversity Oriented Synthesis Library.

The application of a cell-based growth inhibition on a library of skeletally different glycomimetics allowed for the selection of a hexahydro-2-furo[3,2-][1,4]oxazine compound as candidate inhibitors of MDA-MB-231 cell growth. Subsequent synthesis of analogue compounds and preliminary biological studies validated the selection of a valuable hit compound with a novel polyhydroxylated structure for the modulation of the breast carcinoma cell cycle mechanism.

Cotton fabric functionalisation with menthol/PCL micro- and nano-capsules for comfort improvement.

Objective: Cotton functionalisation with poly-ɛ-caprolactone (PCL) micro- and nano-capsules containing menthol was carried out with the aim of introducing a long-lasting refreshing sensation.

Materials And Methods: The preparation of the polymer micro- and nano-capsules was carried out by solvent displacement technique. A confined impinging jets mixer was used in order to ensure fast mixing and generate a homogeneous environment where PCL and menthol can self-assemble.

Two-step one-pot synthesis of dihydropyrazinones as Xaa-Ser dipeptide isosteres through morpholine acetal rearrangement.

The synthesis of the uncommon dihydropyrazinone ring was accomplished by a two-step one pot process taking advantage of the ring rearrangement of N-acylated morpholine acetal derived from serine under acidic treatment in the presence of 2,6-lutidine. The mechanism involves an N-acyl iminium intermediate resulting from morpholine acetal ring opening, which occurs after a nucleophilic attack of the amino acid nitrogen atom to the acetal carbonyl atom. X-Ray diffraction analysis of the dihydropyrazinone, which may be exploited as a constrained Xaa-Ser dipeptide isostere, showed a planar assembly and the internal side-chain in axial orientation with respect to the cyclic molecular scaffold.

A multicenter phase II study of induction chemotherapy with FOLFOX-4 and cetuximab followed by radiation and cetuximab in locally advanced oesophageal cancer.

Background: Preoperative chemoradiotherapy (CRT) improves the survival of patients with oesophageal cancer when compared with surgery alone.

Methods: We conducted a phase II, multicenter trial of FOLFOX-4 and cetuximab in patients with locally advanced oesophageal cancer (LAEC) followed by daily radiotherapy (180 cGy fractions to 5040 cGy) with concurrent weekly cetuximab. Cytokines levels potentially related to cetuximab efficacy were assessed using multiplex-bead assays and enzyme-linked immunosorbent assay at baseline, at week 8 and at week 17.

Soil subsampling in environmental sciences: the role of granulometry.

Uncertainty associated to analytical results is an issue of major interest for the whole analytical community. A large effort has been made to improve analytical techniques and procedures aimed to achieve a well characterized uncertainty associated with analysis. However, it is becoming increasingly recognised that uncertainty deriving from sampling and subsampling can even dominate the global uncertainty budget.

PTCA determination in human hair: reliability and analytical aspects.

Background: In this study we analysed the reliability of HPLC determination of 2.3.5-pyrroletricarboxylic acid (PTCA).

Near infrared spectroscopy as a tool for the determination of eumelanin in human hair.

Eumelanins are brown-black pigments present in the hair and in the epidermis which are acknowledged as protection factors against cell damage caused by ultraviolet radiation. The quantity of eumelanin present in hair has recently been put forward as a means of identifying subjects with a higher risk of skin tumours. For epidemiological studies, chromatographic methods of determining pyrrole-2,3,5-tricarboxylic acid (PTCA; the principal marker of eumelanin) are long, laborious and unsuitable for screening large populations.

Degumming of silk fabric with several proteases.

A crêpe silk fabric was treated with different alkaline (3374-L, GC 897-H), neutral (3273-C), and acid (EC 3.4 23.18) proteases with the aim to study their effectiveness as degumming agents.

Acute inflammatory events and ischemic stroke subtypes.

Background: Recent studies have suggested that previous infection may be a risk factor for ischemic stroke mainly in young and middle-aged patients. The present study sought to further investigate the association between recent inflammatory events (IE) and ischemic stroke without age restriction and to determine the role of recent IE in different ischemic stroke subtypes.

Methods: We performed a case-control study with 93 consecutive hospitalized stroke patients and 200 (107 hospital and 93 community) controls.

Orientation at night: an innate moon compass in sandhoppers (Amphipoda: Talitridae).

The supralittoral amphipod Talitrus saltator is well known for its capacity for astronomical orientation using the sun and moon as compasses. It has also been demonstrated that the sun compass is innate in this species. In our experiments, we released inexpert (naive) young born in the laboratory into a confined environment under the full moon and in the absence of the horizontal component of the magnetic field.

Aetiologic diagnosis of ischaemic stroke in the emergency department: relevance for triage and clinical management.

Effective strategies for the aetiologic diagnosis in patients with ischaemic stroke can be implemented based on simple clinical criteria and instrumental tests which can be performed in a modern emergency room (ER) within 24 hours from admission. This may bear prognostic and therapeutic relevance for patients with acute stroke. Therefore, in this study we set out to establish the feasibility and accuracy of the aetiologic diagnosis of ischaemic stroke in an ER.