Discovery of a New Class of 1-(4-Sulfamoylbenzoyl)piperidine-4-carboxamides as Human Carbonic Anhydrase Inhibitors

A series of 1-(4-sulfamoylbenzoyl)piperidine-4-carboxamides deriving from substituted piperazines/benzylamines was designed, synthesized, and tested on human carbonic anhydrase (hCA). The inhibitory activity of the new sulfonamides was analyzed using acetazolamide (AAZ) as a standard inhibitor against hCA I, II, IX, and XII. Several sulfonamides showed both inhibitory activity at low nanomolar concentrations and selectivity against the cytosolic hCA II isoform, and the same trend was observed on the tumor-associated hCA IX and XII. The benzenesulfonamido carboxamides 11 and 15 were the most potent of the piperazino- and benzylamino-based series, respectively. Docking and molecular dynamics studies related the high selectivity of compound 11 toward the tumor-associated hCA isoforms to its capability to participate in favorable interactions within hCA IX and hCA XII active sites, whereas no such interactions were detected within both hCA I and hCA II isoforms

Electrification of Vessels for Garbage Collection and Treatment in Venice Lagoon

Nowadays, reducing pollutant emissions is of fundamental importance. In particular, in areas where urban public transport is carried out almost exclusively by boats, these represent the primary factors on which it is necessary to intervene. The conversion of current diesel units into hybridpropelled ones is essential to preserve the marina and the environment in areas considered UNESCO heritage sites such as Venice. This document concerns the study of the first hybrid vessel built for garbage collection in the old town of Venice. Paying attention to the system engineering innovations and the results of the tests carried out on board, the authors present some considerations regarding the changes necessary to convert the current diesel propulsion into a hybrid one, with the aim to enable navigation in Zero Emission Mode

Thermoplastic Materials for the Metal Replacement of Non-Structural Components in Marine Engines

Metal replacements for automotive and aerospace components are already a consolidated reality, in light of the advantages offered by fibre-reinforced polymers, consisting of reduced costs, weight, and environmental impact. As a result, engineering has been studying the possibility of replacing currently used metallic alloys with alternative materials, such as thermoplastic fibre-reinforced polymers, in the manufacturing of non-structural sections of marine engines. Given the peculiar characteristics of the working environment of such parts, i.e., ship engine spaces, and the strict requirements regarding safety, the selection of the polymer must be properly performed through a tailored material design process. Consequently, the redesign of the components must be carried out with the aim of exploiting the best of the materials’ properties while ensuring the correct resistance and simplifying installation operations. In this framework, finite element simulations may represent a suitable approach to validate the conformity of the proposed material and design. In this paper, this methodology is applied to a camshaft cover of a four-stroke marine engine, currently made of aluminium alloy. A 30% wt GFs/PA6,6 was identified as the most promising material and the novel plastic cover proved to guarantee the correct resistance while ensuring an important reduction in weight, processing costs, and required energy

Expression of verocytotoxic Escherichia coli antigens in tobacco seeds and evaluation of gut immunity after oral administration in mouse model

Verocytotoxic Escherichia (E.) coli strains are responsible for swine oedema disease, which is an enterotoxaemia that causes economic losses in the pig industry. The production of a vaccine for oral administration in transgenic seeds could be an efficient system to stimulate local immunity. This study was conducted to transform tobacco plants for the seed-specific expression of antigenic proteins from a porcine verocytotoxic E. coli strain. Parameters related to an immunological response and possible adverse effects on the oral administration of obtained tobacco seeds were evaluated in a mouse model. Tobacco was transformed via Agrobacteium tumefaciens with chimeric constructs containing structural parts of the major subunit FedA of the F18 adhesive fimbriae and VT2e B-subunit genes under control of a seed specific GLOB promoter. We showed that the foreign Vt2e-B and F18 genes were stably accumulated in storage tissue by the immunostaining method. In addition, Balb-C mice receiving transgenic tobacco seeds via the oral route showed a significant increase in IgA-positive plasma cell presence in tunica propria when compared to the control group with no observed adverse effects. Our findings encourage future studies focusing on swine for evaluation of the protective effects of transformed tobacco seeds against E. coli infection

Surgical Treatment Strategies and Prognosis of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC is the fifth most common cause of mortality worldwide and the third cancer related cause and is responsible for about 1 million deaths yearly [1]. The ageadjusted worldwide incidence is 5.5-14.9 per 100.000 population. In some areas of the world, such as sub-Saharan Africa and Southeast Asia, HCC represents the first cause of cancer death with an incidence of 52 per 100.000. Furthermore, in Europe and USA, HCC incidence has progressively raised in the past decade representing a burden problem. HCC is one of the few cancers for which a number of risk factors are known in great detail [2, 3]. HCC is almost always (80%) associated with cirrhosis, at least in developed countries, and chronic hepatitis C and B infection, alcoholic cirrhosis and haemocromatosis are some of the established risk factors [4]. The metabolic syndrome related to hypertension, central obesity, diabetes and obesity has been identified as a new risk factor. As a result, screening programs have developed, with the use of ultrasound and \u3b1-fetoprotein (AFP), with a hope to increase the chances of diagnosing small HCC and unltimately increase the rate of curability. Definitive diagnosis relies on the demonstration of a typical vascular pattern per liver imaging techniques (triple-phase CT-scan or MRI) of tumors larger than 2 cm with arterial hypervascularity and venous wash- out. Nodules, smaller than 2 cm, should be rechecked every six months or, if highly suspect, subjected to needle biopsy. It\u2019s likely that the study of tumor-specific tissue markers with prognostic value could introduce a systematic use of needle biopsy. Over the past 20 years, surgical treatment of hepatocellular carcinoma has seen an immense boost and improvement, with good survival outcomes and reduced morbidity and mortality.Liver resection (LR) and orthotopic liver transplantation (OLT) and ablative therapies are now considered the only potentially curative treatments for this cancer. LR has achieved improvement in survival within the past decade as a result of advances in diagnosis, surgical management of HCC and perioperative care. However, the long-term prognosis remains poor, and the 5-year overall survival rate ranges between 33% and 44%, with a 5-year cumulative recurrence rate of 80% to 100%. OLT could be viewed as the optimal treatment for HCC that is accompanied by advanced cirrhosis because of the widest possible resection margins for tumour and for a definitive cure of cirrhosis and its related complications. OLT for HCC performed within well-defined oncologic criteria (Milan criteria \u201creference\u201d) has shown long-term results comparable with those of transplantation for non-HCC patients. However, the critical shortage of available donated organs, together with the increasing number of patients awaiting transplantation, makes this therapeutic option available to only a small percentage of patients. Owing to the limited organ supply, many liver transplant centers usually make a selection to resect patients with compensated liver cirrhosis, defined as Child\u2013Pugh A chronic liver disease and resectable tumor and to reserve transplantation for those with impaired liver function (Child-Pugh class B-C) and small oligonodular HCC considered within the currently accepted criteria for transplantation. Radiofrequency and microwave ablation are relatively new percutaneous techniques in clinical use for HCC, that can produce tumour necrosis. Complete response rates are high in large series if tumour is less that 3 cm in diameter. This chapter will consider the main surgical techniques for the treatment of HCC in the light of the major guidelines currently available and of personal experience. Also, we will review HCC prognostic factors, and the particular situation of \u201clarge\u201d HCC and the strategy for liver tumours located at the hepato-caval confluence

Investigation on Hydrazonobenzenesulfonamides as Human Carbonic Anhydrase I, II, IX and XII Inhibitors

A small series of hydrazonobenzenesulfonamides was designed, synthesized and studied for their human carbonic anhydrase (hCA) inhibitory activity. The synthesized compounds were evaluated against hCA I, II, IX and XII isoforms using acetazolamide (AAZ) as the standard inhibitor. Various hydrazonosulfonamide derivatives showed inhibitory activity at low nanomolar levels with selectivity against the cytosolic hCA II isoform, as well as the transmembrane, tumor-associated enzymes hCA IX and XII. The most potent and selective hydrazones 8, 9, 10, 11, 19 and 24 were docked into isoforms I, II, IX and XII to better understand their activity and selectivity for the different CA isoforms

Violacein, an indole-derived purple-colored natural pigment produced by Janthinobacterium lividum, inhibits the growth of head and neck carcinoma cell lines both in vitro and in vivo

Violacein (VIO; 3-[1,2-dihydro-5-(5-hydroxy-1H-indol-3-yl)-2-oxo-3H-pyrrol-3-ylidene]-1,3-dihydro-2H-indol-2-one), an indole-derived purple-colored pigment, produced by a limited number of Gram-negative bacteria species, including Chromobacterium violaceum and Janthinobacterium lividum, has been demonstrated to have anti-cancer activity, as it interferes with survival transduction signaling pathways in different cancer models. Head and neck carcinoma (HNC) represents the sixth most common and one of the most fatal cancers worldwide. We determined whether VIO was able to inhibit head and neck cancer cell growth both in vitro and in vivo. We provide evidence that VIO treatment of human and mouse head and neck cancer cell lines inhibits cell growth and induces autophagy and apoptosis. In fact, VIO treatment increased PARP-1 cleavage, the Bax/Bcl-2 ratio, the inhibition of ERK1 and ERK2 phosphorylation, and the expression of light chain 3-II (LC3-II). Moreover, VIO was able to induce p53 degradation, cytoplasmic nuclear factor kappa B (NF-κB) accumulation, and reactive oxygen species (ROS) production. VIO induced a significant increase in ROS production. VIO administration was safe in BALB/c mice and reduced the growth of transplanted salivary gland cancer cells (SALTO) in vivo and prolonged median survival. Taken together, our results indicate that the treatment of head and neck cancer cells with VIO can be useful in inhibiting in vivo and in vitro cancer cell growth. VIO may represent a suitable tool for the local treatment of HNC in combination with standard therapies

Syntheses, reactivity, and biological applications of coumarins

This comprehensive review, covering 2021–2023, explores the multifaceted chemical and pharmacological potential of coumarins, emphasizing their significance as versatile natural derivatives in medicinal chemistry. The synthesis and functionalization of coumarins have advanced with innovative strategies. This enabled the incorporation of diverse functional fragments or the construction of supplementary cyclic architectures, thereby the biological and physico-chemical properties of the compounds obtained were enhanced. The unique chemical structure of coumarine facilitates binding to various targets through hydrophobic interactions pi-stacking, hydrogen bonding, and dipole-dipole interactions. Therefore, this important scaffold exhibits promising applications in uncountable fields of medicinal chemistry (e.g., neurodegenerative diseases, cancer, inflammation)

The Coordinated Power Control of Flexible DC Microgrids in Sustainably Optimized Yacht Marinas

Nowadays, the industrial world is undergoing a disruptive transformation towards more environmentally sustainable solutions. In the blue economy, this new approach is not only expressed in the domain of actual vessels, but also in the development of charging infrastructure, displaying a notable transition towards more eco-friendly solutions. The key focus lies in adopting flexible power systems capable of integrating renewable energy sources and storage technologies. Such systems play a crucial role in enabling a shift towards low-emission maritime transport. The emissions reduction goal extends beyond onboard shipboard distribution systems, encompassing also the design of supplying platforms and marinas. This study explores the implementation of a controlled DC microgrid tailored to efficient management of power flows within a yacht marina. Once having established the interfaces for the vessels at berth, the integration between the vessels, the onshore photovoltaic plant and the battery storage unit is made possible thanks to the coordinated management of multiple power converters. The overarching goal is to curtail reliance on external energy sources. Within this DC microgrid framework, a centralized controller assumes a pivotal role in orchestrating the power sources and loads. This coordinated management is essential to achieve sustainable operations, ultimately leading to the reduction of emissions from both ships and onshore power plants

Characterization and effect of year of harvest on the nutritional properties of three varieties of white lupine (Lupinus albus L.)

BACKGROUND: Three cultivars of Lupinus albus L. (Lutteur, Lublanca and Multitalia) were assessed for proximate composition, fatty acids, alkaloids and in vitro fermentation characteristics over three harvest years. RESULTS: The chemical composition varied greatly during the three harvest years. Crude protein content ranged from 353 to 456 g kg-1 dry matter (DM), neutral detergent fiber content from 209 to 321 g kg-1 DM and lignin content from 3.0 to 63.9 g kg-1 DM. Lublanc showed the highest crude protein (417 g kg-1 DM) and lignin (35 g kg-1 DM) contents. High levels of lipids (89.9gkg-1 DM) and starch (93.3 g kg-1 DM) were found in all samples. Alkaloid content ranged from 3.63 to 165mg per 100g. Lutteur and Lublanc showed more favorable n-3/n-6 polyunsaturated fatty acid ratios (from 0.44 to 0.73) and lower values of the anti-quality factor 'erucic acid' (from 5.8 to 20.9 g kg-1) than Multitalia. Lutteur showed higher degradability (897 g kg-1), gas production (330 mL g-1 organic matter (OM)) and volatile fatty acid production (117mmolg-1 OM) than the other varieties. CONCLUSION: The present data suggest L. albus L. cv. Lutteur to be a promising crop as food thanks to its high nutritive traits and most constant yield over time