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In this paper, we present a case study on freight railway transportation in Italy, which is a by-product of research collaboration with a major Italian railway company. We highlight the main features of the Italian reality and propose a customized mathematical model to design the service network, that is, the set of origin-destination connections. More specifically, the model suggests the services to provide, the number of trains travelling on each connection, the number of cars and their type. We consider both full and empty freight car movements and take handling costs into account. All decisions are taken in order to minimize the total costs. The quality of service is guaranteed by satisfying all the transportation demand and by implicitly minimizing the waiting time of cars at intermediate railway stations. Our approach yields to a multi-commodity network design problem with a concave cost function. To solve this problem, we implement a specialized tabu search procedure. Computational results on realistic instances show a significant improvement over current practice. [ABSTRACT FROM AUTHOR]

The cross-talk between plant-derived nanovesicles (PDNVs) and mammalian cells has been explored by several investigations, underlining the capability of these natural nanovesicles to regulate several molecular pathways. Additionally, PDNVs possess biological proprieties that make them applicable against pathological conditions, such as hepatic diseases. In this study we explored the antioxidant properties of lemon-derived nanovesicles, isolated at laboratory (LNVs) and industrial scale (iLNVs) in human healthy hepatocytes (THLE-2) and in metabolic syndrome induced by a high-fat diet (HFD) in the rat. Our findings demonstrate that in THLE-2 cells, LNVs and iLNVs decrease ROS production and upregulate the expression of antioxidant mediators, Nrf2 and HO-1. Furthermore, the in vivo assessment reveals that the oral administration of iLNVs improves glucose tolerance and lipid dysmetabolism, ameliorates biometric parameters and systemic redox homeostasis, and upregulates Nrf2/HO-1 signaling in HFD rat liver. Consequently, we believe LNVs/iLNVs might be a promising approach for managing hepatic and dysmetabolic disorders., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest that could be perceived as prejudicing the impartiality of the research reported. The authors S.R., A.C., and R.A. are cofounders of Navhetec, an Academic Spin-Off of the University of Palermo that only provides the nanovesicle extracts but that did not have any role in the conceptualization of this article and the analysis of the results. The same authors are inventors of the Italian patents 102019000005090 and 102015902344749., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: A wealth of evidence underscores the bioactive properties of nutraceuticals and functional foods in addressing oxyinflammatory-based diseases with implications at both peripheral and central levels. Opuntia ficus-indica (OFI) is well-documented for its health-promoting attributes, though its fruit (OFIF) remains relatively understudied. Not only poses Metabolic Syndrome (MetS) cardiometabolic risks but also contributes significantly to cognitive impairment, especially in crucial brain areas such as hippocampus and hypothalamus., Methods: Following 8 weeks of HFD to induce MetS, rats received OFIF oral supplementation for 4 weeks to evaluate cognitive and affective modifications using behavioural paradigms, i.e. open field, burrowing, white-dark box, novelty-suppressed feeding, and object recognition tests. Our investigation extended to biochemical evaluations of lipid homeostasis, central and peripheral oxidative stress and neurotrophic pathways, correlating these measures together with circulating leptin levels., Results: Our data revealed that OFIF modulation of leptin positively correlates with systemic and brain oxidative stress, with markers of increased anxiety-like behaviour and impaired lipid homeostasis. On the other hand, leptin levels reduced by OFIF are associated with improved antioxidant barriers, declarative memory and neurotrophic signalling., Discussion: This study underscores OFIF neuroactive potential in the context of MetS-associated cognitive impairment, offering insights into its mechanisms and implications for future therapeutic strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Brain-derived neurotrophic factor (Bdnf ) expression is tightly controlled at the transcriptional and post-transcriptional levels. Previously, we showed that inhibition of noncoding Bdnf antisense ( Bdnf -AS) RNA upregulates Bdnf protein. Here, we generated a Bdnf -antisense knockout ( Bdnf- AS KO) mouse model by deleting 6 kilobases upstream of Bdnf -AS. After verifying suppression of Bdnf- AS, baseline behavioral tests indicated no significant difference in knockout and wild type mice, except for enhanced cognitive function in the knockout mice in the Y-maze. Following acute involuntary exercise, Bdnf -AS KO mice were re-assessed and a significant increase in Bdnf mRNA and protein were observed. Following long-term involuntary exercise, we observed a significant increase in nonspatial and spatial memory in novel object recognition and Barnes maze tests in young and aged Bdnf- AS KO mice. Our data provides evidence for the beneficial effects of endogenous Bdnf upregulation and the synergistic effect of Bdnf -AS knockout on exercise and memory retention., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Author(s).)

Single-strand breaks (SSBs) represent the major form of DNA damage, yet techniques to map these lesions genome-wide with nucleotide-level precision are limited. Here, we present a method, termed SSiNGLe, and demonstrate its utility to explore the distribution and dynamic changes in genome-wide SSBs in response to different biological and environmental stimuli. We validate SSiNGLe using two very distinct sequencing techniques and apply it to derive global profiles of SSBs in different biological states. Strikingly, we show that patterns of SSBs in the genome are non-random, specific to different biological states, enriched in regulatory elements, exons, introns, specific types of repeats and exhibit differential preference for the template strand between exons and introns. Furthermore, we show that breaks likely contribute to naturally occurring sequence variants. Finally, we demonstrate strong links between SSB patterns and age. Overall, SSiNGLe provides access to unexplored realms of cellular biology, not obtainable with current approaches.

A number of observations indicate that heavy metals are able to alter cellular metabolic pathways through induction of a prooxidative state. Nevertheless, the outcome of heavy metal-mediated effects in the development of human diseases is debated and needs further insights. Cancer is a well-established DNA mutation-linked disease; however, epigenetic events are perhaps more important and harmful than genetic alterations. Unfortunately, we do not have reliable screening methods to assess/validate the epigenetic (promoter) effects of a physical or a chemical agent. We propose a mechanism of action whereby mercury acts as a possible promoter carcinogen. In the present contribution, we resume our previous studies on mercury tested at concentrations comparable with its occurrence as environmental pollutant. It is shown that Hg(II) elicits a prooxidative state in keratinocytes linked to inhibition of gap junction-mediated intercellular communication and proinflammatory cytokine production. These combined effects may on one hand isolate cells from tissue-specific homeostasis promoting their proliferation and on the other hand tamper the immune system defense/surveillance checkmating the whole organism. Since Hg(II) is not a mutagenic/genotoxic compound directly affecting gene expression, in a broader sense, mercury might be an example of an epigenetic tumor promoter or, further expanding this concept, a "metagenetic" effector.

The aim of this paper is to describe and discuss, on the basis of a thorough review of the literature, the case of a 70-year-old woman with probable cirrhosis secondary to chronic hepatitis B and C, uncomplicated portal hypertension (without ascites, encephalopathy or bleeding varices), splenomegaly and hypersplenism, and an unusual, spontaneous, large splenorenal shunt and recanalization of the umbilical vein. The tortuous and varicose splenorenal shunt was diagnosed by abdominal ultrasound and CT investigations. A duplex Doppler ultrasonography evaluation was performed to study shunt flow direction and velocity. No gastroesophageal varices were identified on endoscopic examination. The clinical relevance of spontaneous splenorenal shunt, often associated with fundic gastric varices, is discussed.

The aim of this paper is to describe and discuss, on the basis of the available literature, the case of an old female patient, admitted to our university hospital because of a severe dysphagia for solid foods, in whom laboratory data showed a marked hypomagnesemia. She reported a long history (20 years) of allergic bronchial asthma treated with theophylline. Esophagography evidenced a disorder of esophagus motility with diffuse multiple spasm, reminiscent of the 'corkscrew esophagus'. A link with the severe hypomagnesemia (Mg 1.1 mEq/l, normal range 1.6-2.1) was suspected, and a therapy with oral pidolate of Mg (1.5 g/twice a day) was started and continued for 4 months. This was associated with a slow progressive normalization of the Mg plasma level and reverted radiographic esophageal findings with disappearance of dysphagia. Mg is an important element for health and disease, and today Mg deficiency in man has become an accepted medical problem which might complicate many diseases. Neuromuscular disorders, as laryngeal spasm, are recognized complications of hypomagnesemia, but until now only 1 case of motor esophageal disorder associated with a low Mg plasma level was briefly reported in the literature, even if dysphagia is generally included in the symptomatological pattern of hypomagnesemia. Our observation of a severe form of esophageal spasm, associated with hypomagnesemia, in an aged female patient underlines the pathophysiological meaning of the plasma Mg level and suggests the need for routine Mg determination in the clinical setting.

Diffuse and symptomatic lipomatosis of the colon, particularly when associated with hyperplasia of the appendices epiploicae, is a rare disease. We report here the case of a lean, 26-year-old woman who had polypoid lipomatosis of the colon with submucosal and subserous expression (involving the mesentery and peritoneum) associated with extreme hyperplasia of the appendices epiploicae. Her disease led to a recurrent subocclusive syndrome which required total colectomy. We discuss the case and review the literature on this subject. The particular characteristics of this case and early onset of disease would suggest that our patient was affected by a congenital lipomatous syndrome linked to mesenchymal dysplasia. Long-term monitoring will enable prompt intervention in the case of reformation of lipomatous tissue.