Extensive Molecular Dynamics Simulations Disclosed the Stability of mPGES-1 Enzyme and the Structural Role of Glutathione (GSH) Cofactor

A deep in silico investigation of various microsomal prostaglandin E-2 synthase-1 (mPGES-1) protein systems is here reported using molecular dynamics (MD) simulations. Firstly, eight different proteins models (Models A-H) were built, starting from the active enzyme trimer system (Model A), namely that bound to three glutathione (GSH) cofactor molecules, and then gradually removing the GSHs (Models B-H), simulating each of them for 100 ns in explicit solvent. The analysis of the obtained data disclosed the structural role of GSH in the chemical architecture of mPGES-1 enzyme, thus suggesting the unlikely displacement of this cofactor, in accordance with experimentally determined protein structures co-complexed with small molecule inhibitors. Afterwards, Model A was submitted to microsecond-scale molecular dynamics simulation (total simulation time=10 mu s), in order to shed light about the dynamical behaviour of this enzyme at atomic level and to obtain further structural features and protein function information. We confirmed the structural stability of the enzyme machinery, observing a conformational rigidity of the protein, with a backbone RMSD of similar to 3 angstrom along the simulation time, and highlighting the strong active contribution of GSH molecules due to their active role in packing the protein chains through a tight binding at monomer interfaces. Furthermore, the focused analysis on R73 residue disclosed its role in solvent exchange events, probably excluding its function as route for GSH to enter towards the endoplasmic reticulum membrane, in line with the recently reported function of cap domain residues F44-D66 as gatekeeper for GSH entrance into catalytic site

Recent Advances in Endocrine Disrupting Compounds Degradation through Metal Oxide-Based Nanomaterials

Endocrine Disrupting Compounds (EDCs) comprise a class of natural or synthetic molecules and groups of substances which are considered as emerging contaminants due to their toxicity and danger for the ecosystems, including human health. Nowadays, the presence of EDCs in water and wastewater has become a global problem, which is challenging the scientific community to address the development and application of effective strategies for their removal from the environment. Particularly, catalytic and photocatalytic degradation processes employing nanostructured materials based on metal oxides, mainly acting through the generation of reactive oxygen species, are widely explored to eradicate EDCs from water. In this review, we report the recent advances described by the major publications in recent years and focused on the degradation processes of several classes of EDCs, such as plastic components and additives, agricultural chemicals, pharmaceuticals, and personal care products, which were realized by using novel metal oxide-based nanomaterials. A variety of doped, hybrid, composite and heterostructured semiconductors were reported, whose performances are influenced by their chemical, structural as well as morphological features. Along with photocatalysis, alternative heterogeneous advanced oxidation processes are in development, and their combination may be a promising way toward industrial scale application

Re-designing Dynamic Content Delivery in the Light of a Virtualized Infrastructure

We explore the opportunities and design options enabled by novel SDN and NFV technologies, by re-designing a dynamic Content Delivery Network (CDN) service. Our system, named MOSTO, provides performance levels comparable to that of a regular CDN, but does not require the deployment of a large distributed infrastructure. In the process of designing the system, we identify relevant functions that could be integrated in the future Internet infrastructure. Such functions greatly simplify the design and effectiveness of services such as MOSTO. We demonstrate our system using a mixture of simulation, emulation, testbed experiments and by realizing a proof-of-concept deployment in a planet-wide commercial cloud system.Comment: Extended version of the paper accepted for publication in JSAC special issue on Emerging Technologies in Software-Driven Communication - November 201

The CSR committee as moderator for the ESG score and market value

This paper investigates the relationship between the ESG score and market values. Specifically, we test the moderating role of CSR committee defined as organizational subcommittees of boards of directors that make social and environmental recommendationsto the boards of directors and support members in their CSR-related tasks. We built a panel data set with all the listed companies in STOXX Europe 600, covering the period 2014–2020. Firms' data come from Refinitiv Eikon database which contains financial and ESG scores data of all EU listed companies. Our sample of firm-level data contains a dataset of 600 European listed companies which are part of the STOXX Europe 600 Index. We included ESG data of STOXX Europe 600 Index components in the period 2014–2020. Our dataset contains a total of 4800 firm-year observations. We found a negative relationship between ESG score and stock prices while the presence of CSR committee as moderating variable generates no significant evidence of ESG score. The presence of CSR committee is not considerably supporting ESG in achieving higher market performance. The CSR committee plays an essential role in monitoring management activities. This may support management practitioners in better understanding and reacting to stakeholder expectations

Stereochemical analysis of natural products. Approaches relying on the combination of NMR spectroscopy and computational methods

Abstract The stereochemical study of flexible stereogenic carbon chains, such as those of many novel natural products, is a particularly challenging task. Recent applications of our group on the so-called "J-based approach", a methodology relying on a detailed analysis of homonuclear (H-H) and heteronuclear (C-H) 2,3 J couplings, include the study of the sphinxolide family of antitumor macrolides, a group of molecules characterized by a flexible macrocyclic framework bearing a number of oxygenated and methylated undetermined stereocenters, and of ascaulitoxin, a nitrogen-containing phytotoxin with herbicidal activity produced by a phytopathogenic fungus. An extension of the original procedure, relying on a Hartree-Fock (HF) ab initio calculation of conformational equilibrium and an estimate of the Boltzmann averaged 2,3 JHH and 2,3 JCH couplings, has been applied to the stereochemical study of sapinofuranone A, where the conformational equilibrium among existing rotamers had initially led to controversial results. 13C NMR chemical shifts are additional useful parameters in the study of complex organic molecules. Along these lines, we have lately proposed the use of Hartree–Fock gauge including atomic orbitals (GIAO) calculated 13C NMR chemical shift values as a supporting tool for the validation of the structure of new natural products and the determination of the relative stereochemistry of diastereomeric flexible compounds that are characterized by multiple conformer equilibria

New technologies in the surgical management of endometriosis

Introduction: Endometriosis is a very common disease that affects up to 10% of the female population. Although medical therapy represents the first-line treatment for endometriosis, it does not always manage to control symptoms. Laparoscopy represents the standard surgical treatment in endometriosis. Robotic-assisted laparoscopy is an innovative mini-invasive surgical technique. Its application in gynecological surgery and in endometriosis has increased in the last decade. Our purpose is to offer an overview of the role of robotic-assisted laparoscopy in the surgical treatment of endometriosis. Methods: We evaluated studies dealing with the new technique in surgery for endometriosis with a focus on robotic surgery. We performed a compressive literature research on PubMed and the Cochrane Library in December 2022. Expert opinion: Robotic-assisted surgery is a feasible and safe approach to endometriosis surgery and is superimposable to laparoscopy in terms of complication rate, blood loss, hospitalization, and long-term improvement of symptoms. The effect of robotic-assisted surgery on operative time is still contradictory and needs to be further investigated. Robotic-assisted laparoscopic surgery can provide particular benefit in the management of women with severe endometriosis secondary to its advantage in surgical precision and ergonomics. Indocyanine green fluorescence angiography could be useful to assist in the vascularization of ureters and bowel anastomosis, to prevent postoperative complication and leakage

Chronic Endometritis

Chronic endometritis is a persistent inflammation of the inner lining of the uterine cavity. Several studies have demonstrated that it is a condition frequently associated with repeated unexplained implantation failure at in vitro fertilization, recurrent miscarriage, as well as poor obstetric outcomes such as preterm labor