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In this study, we present the design, simulation, and implementation of a DC-DC synchronous buck converter utilizing IISB's 2 μ m 4H-silicon carbide (SiC) complementary metal–oxide–semiconductor (CMOS) technology. The converter is designed to meet the demands of modern integrated circuits, particularly in the field of integrated power management. The SiC technology offers enhanced performance and reliability at high temperatures, making it especially suitable for applications that operate in these conditions, including automotive systems, and aerospace, among others. The power transistors and gate drivers are fully integrated on-chip, optimizing efficiency and minimizing footprint. Additionally, the study contributes to the understanding of SiC technology and its application in integrated circuit design. Simulation results demonstrate a peak efficiency of 86.6% at 120 mA load current and 84.8% at 300 mA load current, showing the converter performance under different operating conditions. Furthermore, at high temperatures (295 °C), the converter achieves an efficiency of 89.6%, demonstrating its robustness and versatility in extreme environments. These findings contribute to the advancement of integrated circuit design and facilitate advancements in more efficient and robust power management solutions. [ABSTRACT FROM AUTHOR]

From an agricultural perspective, carrots are a significant tap root vegetable crop in the Apiaceae family because of their nutritional value, health advantages, and economic importance. The edible part of a carrot, known as the storage root, contains various beneficial compounds, such as carotenoids, anthocyanins, dietary fiber, vitamins, and other nutrients. It has a crucial role in human nutrition as a significant vegetable and raw material in the nutraceutical, food, and pharmaceutical industries. The cultivation of carrot fields is susceptible to a wide range of biotic and abiotic hazards, which can significantly damage the plants' health and decrease yield and quality. Scientific research mostly focuses on important biotic stressors, including pests, such as nematodes and carrot flies, as well as diseases, such as cavity spots, crown or cottony rot, black rot, and leaf blight, caused by bacteria, fungi, and oomycetes. The emerging challenges in the field include gaining a comprehensive understanding of the interaction between hosts and pathogens in the carrot–pathogen system, identifying the elements that contribute to disease development, expanding knowledge of systemic treatments, exploring host resistance mechanisms, developing integrated control programs, and enhancing resistance through breeding approaches. In fact, the primary carrot-growing regions in tropical and subtropical climates are experiencing abiotic pressures, such as drought, salinity, and heat stress, which limit carrot production. This review provides an extensive, up-to-date overview of the literature on biotic and abiotic factors for enhanced and sustainable carrot production, considering the use of different technologies for the shelf-life extension of carrots. Therefore, it addresses the current issues in the carrot production chain, opening new perspectives for the exploration of carrots both as a food commodity and as a source of natural compounds. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignancy in the female sex; although recent therapies have significantly changed the natural history of this cancer, it remains a significant challenge. In the past decade, evidence has been put forward that some oncogenic viruses may play a role in the development of sporadic breast cancer; however, data are scattered and mostly reported as sparse case series or small case–control studies. In this review, we organize and report current evidence regarding the role of high-risk human papillomavirus, mouse mammary tumor virus, Epstein–Barr virus, cytomegalovirus, bovine leukemia virus, human polyomavirus 2, and Merkel cell polyomavirus in the pathogenesis of breast cancer. [ABSTRACT FROM AUTHOR]

Cystinosis is a rare lysosomal storage disorder caused by autosomal recessive mutations in the CTNS gene that encodes for the cystine transporter cystinosin, which is expressed on the lysosomal membrane mediating the efflux of cystine. Cysteamine bitartrate is a cystine-depleting aminothiol agent approved for the treatment of cystinosis in children and adults. In this study, we developed and validated a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for the determination of cysteamine levels in plasma samples. This LC-MS/MS method was validated according to the European Medicines Agency (EMA)'s guidelines for bioanalytical method validation. An ultra-performance liquid chromatograph (UPLC) coupled with a 6470 mass spectrometry system was used for cysteamine determination. Our validated method was applied to plasma samples from n = 8 cystinosis patients (median, interquartile range (IQR) = 20.5, 8.5–26.0 years). The samples were collected before cysteamine oral administration (pre-dose) and 1 h after (post-dose). Our bioanalytical method fulfilled the regulatory guidelines for method validation. The cysteamine plasma levels in pre-dose samples were 2.57 and 1.50–3.31 μM (median and IQR, respectively), whereas the post-dose samples reported a cysteamine median concentration of 28.00 μM (IQR: 17.60–36.61). Our method allows the rapid determination of cysteamine plasma levels. This method was successfully used in cystinosis patients and, therefore, could be a useful tool for the evaluation of therapy adherence and for future pharmacokinetic (PK) studies involving a higher number of subjects. [ABSTRACT FROM AUTHOR]

The antimicrobial activity of Origanum vulgare var. hirtum (O) and Coridothymus capitatus (C) essential oils (EOs) and hydrolates (HYs) of the same botanical species was evaluated on sixteen L. monocytogenes strains from food and clinical origins. The antimicrobial activity was assessed by Minimum Inhibitory Concentration (MIC) determination, viable cell enumeration over time up to 60 min, and evaluation of the cellular damage through Confocal Laser Scanning Microscope (CLSM) analysis. EOs exhibited antimicrobial activity with MIC values ranging from 0.3125 to 10 µL/mL. In contrast, HYs demonstrated antimicrobial effectiveness at higher concentrations (125–500 µL/mL). The effect of HYs was rapid after the contact with the cells, and the cell count reduction over 60 min of HY treatment was about 1.2–1.7 Log CFU/mL. L. monocytogenes cells were stressed by HY treatment, and red cell aggregates were revealed through CLSM observation. Moreover, the combinations of EOs and HYs had an additive antilisterial effect in most cases and allowed the concentration of use to be reduced, while maintaining or improving the antimicrobial effectiveness. The combined use of EOs and HYs can offer novel opportunities for applications, thereby enhancing the antimicrobial effectiveness and diminishing the concentration of use. This provides the added benefit of reducing toxicity and mitigating any undesirable sensory effects. [ABSTRACT FROM AUTHOR]

The dairy industry's contribution to global warming has been thoroughly examined. However, it is important to raise public awareness of emission hotspots and the possibility of mitigation in dairy supply chains. This study assessed the Carbon Footprint (CF) of five dairy products through a cradle-to-grave Life Cycle Assessment approach and evaluated the carbon sink potential of some practices. The functional units were 1 kg of fresh raw milk, yogurt, fresh cheese, mozzarella cheese, and aged cheese. The data collected were related to an extensive dairy farm, a cheese-factory, two markets, a delivery service, and a court of consumers. The CFs were 4.39, 5.10, 9.82, 8.40, and 15.34 kg CO2 eq. for fresh raw milk, yogurt, mozzarella cheese, fresh cheese, and aged cheese, respectively. The hotspots of the dairy supply chain considered herein refer to farm activities and energy consumption, whereas conservative agriculture practices and rotational grazing sequestered 1.60 ± 0.80 kg CO2 eq. per kg of dairy product consumed. The CF was reduced by 0.14 kg CO2 eq. for 1 kg of dairy product delivered at home compared to direct purchasing at a market. The carbon sink capacity of dairy farms appeared as a primary mean for mitigating climate change in the dairy supply chain. [ABSTRACT FROM AUTHOR]

In this paper, we propose a temperature sensor based on a 4H-SiC CMOS oscillator circuit and that is able to operate in the temperature range between 298 K and 573 K. The circuit is developed on Fraunhofer IISB's 2 μm 4H-SiC CMOS technology and is designed for a bias voltage of 20 V and an oscillation frequency of 90 kHz at room temperature. The possibility to relate the absolute temperature with the oscillation frequency is due to the temperature dependency of the threshold voltage and of the channel mobility of the transistors. An analytical model of the frequency-temperature dependency has been developed and is used as a starting point for the design of the circuit. Once the circuit has been designed, numerical simulations are performed with the Verilog-A BSIM4SiC model, which has been opportunely tuned on Fraunhofer IISB's 2 μm 4H-SiC CMOS technology, and their results showed almost linear frequency-temperature characteristics with a coefficient of determination that was higher than 0.9681 for all of the bias conditions, whose maximum is 0.9992 at a V D D = 12.5 V. Moreover, we considered the effects of the fabrication process through a Monte Carlo analysis, where we varied the threshold voltage and the channel mobility with different values of the Gaussian distribution variance. For example, at V D D = 20 V, a deviation of 17.4 % from the nominal characteristic is obtained for a Gaussian distribution variance of 20 % . Finally, we applied the one-point calibration procedure, and temperature errors of +8.8 K and −5.8 K were observed at V D D = 15 V. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB) is the most common extracranial solid tumor during infancy, causing up to 10% of mortality in children; thus, identifying novel early and accurate diagnostic and prognostic biomarkers is mandatory. NB-derived exosomes carry proteins (Exo-prots) reflecting the status of the tumor cell of origin. The purpose of this study was to characterize, for the first time, the Exo-prots specifically expressed in NB patients associated with tumor phenotype and disease stage. We isolated exosomes from plasma specimens of 24 HR-NB patients and 24 low-risk (LR-NB) patients at diagnosis and of 24 age-matched healthy controls (CTRL). Exo-prot expression was measured by liquid chromatography–mass spectrometry. The data are available via ProteomeXchange (PXD042422). The NB patients had a different Exo-prot expression profile compared to the CTRL. The deregulated Exo-prots in the NB specimens acted mainly in the tumor-associated pathways. The HR-NB patients showed a different Exo-prot expression profile compared to the LR-NB patients, with the modulation of proteins involved in cell migration, proliferation and metastasis. NCAM, NCL, LUM and VASP demonstrated a diagnostic value in discriminating the NB patients from the CTRL; meanwhile, MYH9, FN1, CALR, AKAP12 and LTBP1 were able to differentiate between the HR-NB and LR-NB patients with high accuracy. Therefore, Exo-prots contribute to NB tumor development and to the aggressive metastatic NB phenotype. [ABSTRACT FROM AUTHOR]

Simple Summary: Juvenile Idiopathic Arthritis (JIA) is a chronic pediatric arthritis and an important cause of children's disabilities. Despite major therapeutic advancements achieved in the last decades, the lack of diagnostic and predictive biomarkers still hinders JIA patients' clinical management. MicroRNAs (miRNAs) are small nucleic acids whose role in many pathologies has been demonstrated. In particular, miRNAs circulating in patient body fluids represent potential new disease biomarkers. Although more extensively investigated in adult arthritis, the expression and roles of miRNAs have also been studied in JIA. Here, we review the most relevant studies analyzing the expression of miRNAs in patients affected by JIA and evaluate their potential as biomarkers, highlighting the limitations currently affecting miRNA investigation. Juvenile Idiopathic Arthritis (JIA) represents the most common chronic pediatric arthritis in Western countries and a leading cause of disability in children. Despite recent clinical achievements, patient management is still hindered by a lack of diagnostic/prognostic biomarkers and targeted treatment protocols. MicroRNAs (miRNAs) are short non-coding RNAs playing a key role in gene regulation, and their involvement in many pathologies has been widely reported in the literature. In recent decades, miRNA's contribution to the regulation of the immune system and the pathogenesis of autoimmune diseases has been demonstrated. Furthermore, miRNAs isolated from patients' biological samples are currently under investigation for their potential as novel biomarkers. This review aims to provide an overview of the state of the art on miRNA investigation in JIA. The literature addressing the expression of miRNAs in different types of biological samples isolated from JIA patients was reviewed, focusing in particular on their potential application as diagnostic/prognostic biomarkers. The role of miRNAs in the regulation of immune responses in affected joints will also be discussed along with their potential utility as markers of patients' responses to therapeutic approaches. This information will be of value to investigators in the field of pediatric rheumatology, encouraging further research to increase our knowledge of miRNAs' potential for future clinical applications in JIA. [ABSTRACT FROM AUTHOR]

Fruits and vegetables are constantly affected by postharvest diseases, of which anthracnose is one of the most severe and is caused by diverse Colletotrichum species, mainly C. gloeosporioides. In the last few decades, chemical fungicides have been the primary approach to anthracnose control. However, recent trends and regulations have sought to limit the use of these substances. Greener management includes a group of sustainable alternatives that use natural substances and microorganisms to control postharvest fungi. This comprehensive review of contemporary research presents various sustainable alternatives to C. gloeosporioides postharvest control in vitro and in situ, ranging from the use of biopolymers, essential oils, and antagonistic microorganisms to cultivar resistance. Strategies such as encapsulation, biofilms, coatings, compounds secreted, antibiotics, and lytic enzyme production by microorganisms are revised. Finally, the potential effects of climate change on C. gloeosporioides and anthracnose disease are explored. Greener management can provide a possible replacement for the conventional approach of using chemical fungicides for anthracnose postharvest control. It presents diverse methodologies that are not mutually exclusive and can be in tune with the needs and interests of new consumers and the environment. Overall, developing or using these alternatives has strong potential for improving sustainability and addressing the challenges generated by climate change. [ABSTRACT FROM AUTHOR]

In this study, for the first time, the chemical composition of Echinacea purpurea (L.) Moench. and propolis (EAP) hydroalcoholic solution from the Trentino Alto Adige region of northern Italy was investigated by using SPME-GC-MS to describe the volatile content and GC-MS after silylation to detect the non-volatile compounds in the extractable organic matter. The antimicrobial activity of EAP hydroalcoholic solution was evaluated by Minimum Inhibitory Concentration (MIC) determination on 13 type strains, food and clinical isolates. Time Kill Kinetics (TKK) assays and the determination on swimming and swarming motility for 48 h gave more details on the mode of action of EAP solution. The results highlighted the presence of some terpenes and a large number of compounds belonging to different chemical classes. Among these, sugars and organic acids excelled. The EAP hydroalcoholic solution exhibited a strong antimicrobial activity in terms of MIC, with a clear decrease in the cellular load after 48 h. However, the bacterial motility may not be affected by the EAP treatment, displaying a dynamic swarming and swimming motility capacity over time. Given the complexity of chemical profile and the strong antimicrobial effectiveness, the EAP hydroalcoholic solution can be considered a source of bioactive molecules, deserving further investigation for the versatility of application. [ABSTRACT FROM AUTHOR]

Risk-reducing surgery (RRS) is recommended in BRCA-mutated carriers because of their increased risk of developing ovarian cancer, while its role is still discussed for women harboring mutations in non-BRCA homologous repair genes. The aim of this study was to retrospectively evaluate the occurrence of pathological findings in a high-risk population undergoing RRS in San Matteo Hospital, Pavia between 2012 and 2022, and correlate their genetic and clinical outcomes, comparing them with a control group. The final cohort of 190 patients included 85 BRCA1, 63 BRCA2, 11 CHEK2, 7 PALB2, 4 ATM, 1 ERCC5, 1 RAD51C, 1 CDH1, 1 MEN1, 1 MLH1 gene mutation carriers and 15 patients with no known mutation but with strong familial risk. Occult invasive serous carcinoma (HGSC) and serous tubal intraepithelial carcinoma (STIC) were diagnosed in 12 (6.3%) women, all of them BRCA carriers. No neoplastic lesion was diagnosed in the non-BRCA group, in women with familial risk, or in the control group. Oral contraceptive use and age ≤45 at surgery were both found to be favorable factors. While p53 signature and serous tubal intraepithelial lesion (STIL) were also seen in the control group and in non-BRCA carriers, STIC and HGSC were only found in BRCA1/2 mutation carriers. [ABSTRACT FROM AUTHOR]

The interactions between aromatase inhibitors (AI) in breast cancer (BC) and gut microbiota (GM) have not been completely established yet. The aim of the study is to evaluate the bio-diversity of GM and the relationship between GM, inflammation and tumor-infiltrating lymphocytes (TILs) in postmenopausal women with BC during adjuvant AI treatment compared to women with disease relapse during or after one year of AI therapy ("endocrine-resistant"). We conducted a monocenter observational case-control study. Eighty-four women with BC (8 cases, 76 controls) were enrolled from 2019 to 2021. We observed a significant difference in the mean microbial abundance between the two groups for the taxonomic rank of order (p 0.035) and family (p 0.029); specifically, the case group showed higher diversity than the control group. Veillonella reached its maximum abundance in cases (p 0.022). Cytokine levels were compared among the groups created considering the TILs levels. We obtained a statistically significant difference (p 0.045) in IL-17 levels among the groups, with patients with low TILs levels showing a higher median value for IL-17 (0.15 vs. 0.08 pg/mL). Further studies about the bio-diversity in women with BC may lead to the development of new biomarkers and targeted interventions. [ABSTRACT FROM AUTHOR]

Background: Although liver biopsy remains the gold standard for the diagnosis and the monitoring of liver disease, non-invasive biomarkers have been recently suggested to predict liver disease severity, progression, and response to therapy. We investigated multiple tissue and circulating markers of angiogenesis in predicting the severity of biopsy-validated chronic liver diseases in patients with chronic hepatitis C virus (HCV) and in NAFLD/NASH patients. Methods: We studied samples from forty-six patients with HCV and/or NAFLD who underwent liver biopsy, liver ultrasonography, and liver stiffness measurement. Ishak and Brunt scores were calculated. Expression of selective genes and luminex analyses of 17 different circulating pro-angiogenic factors were performed. Results: The phenotype of NAFLD/NASH or HCV subjects was similar, except for insulin, which was expressed at higher levels in NAFLD/NASH patients. A Mann–Whitney test showed significant differences for the circulating levels of HB-EGF and for follistatin between HCV and NAFLD/NASH patients. In HCV patients, we found an inverse correlation between disease stage and BMP-9 and VEGF-A circulating levels, while in NASH/NAFLD direct correlations between stage and BMP-9 and VEGF-A circulating levels were noted. The K-means algorithm divided HCV and NASH/NAFLD patients in two clusters with significant differences between them. Logistic regression models showed a positive relationship with BMP-9 levels for NASH/NAFLD and with HB-EGF circulating concentrations for HCV. ROC analysis showed for BMP-9 > 1188 pg/mL a worse disease in NASH/NAFLD, whereas for HB-EGF < 61 pg/mL a higher severity of disease in HCV. Conclusion: Our data show that circulating biomarker profiles can identify the severity of chronic liver disease of NAFLD/NASH or HCV origin. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic is being questioned for its possible food transmission, due to several reports of the virus on food, outbreaks developed in food companies, as well as its origins linked to the wet market of Wuhan, China. The purpose of this review is to analyze the scientific evidence gathered so far on the relationship between food and the pandemic, considering all aspects of the food system that can be involved. The collected data indicate that there is no evidence that foods represent a risk for the transmission of SARS-CoV-2. In fact, even if the virus can persist on food surfaces, there are currently no proven cases of infection from food. Moreover, the pandemic showed to have deeply influenced the eating habits of consumers and their purchasing methods, but also to have enhanced food waste and poverty. Another important finding is the role of meat processing plants as suitable environments for the onset of outbreaks. Lessons learned from the pandemic include the correct management of spaces, food hygiene education for both food workers and common people, the enhancement of alternative commercial channels, the reorganization of food activities, in particular wet markets, and intensive farming, following correct hygiene practices. All these outcomes lead to another crucial lesson, which is the importance of the resilience of the food system. These lessons should be assimilated to deal with the present pandemic and possible future emergencies. Future research directions include further investigation of the factors linked to the food system that can favor the emergence of viruses, and of innovative technologies that can reduce viral transmission. [ABSTRACT FROM AUTHOR]

P2X7R-NLRP3 and AIM2 inflammasomes activate caspase-1 and the release of cytokines involved in viral-related liver disease. Little is known about their role in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steato-hepatitis (NASH). We characterized the role of inflammasomes in NAFLD, NASH, and HCV. Gene expression and subcellular localization of P2X7R/P2X4R-NLRP3 and AIM2 inflammasome components were examined in histopathological preparations of 46 patients with biopsy-proven viral and metabolic liver disease using real-time PCR and immunofluorescence. P2X7R, P2X4R, and Caspase-1 are two- to five-fold more expressed in patients with NAFLD/NASH associated with chronic HCV infection than those with metabolic damage only (p ≤ 0.01 for all comparisons). The AIM2 inflammasome is 4.4 times more expressed in patients with chronic HCV infection, regardless of coexistent metabolic abnormalities (p = 0.0006). IL-2, a cytokine playing a pivotal role during chronic HCV infection, showed a similar expression in HCV and NASH patients (p = 0.77) but was virtually absent in NAFLD. The P2X7R-NLRP3 complex prevailed in infiltrating macrophages, while AIM2 was localized in Kupffer cells. Caspase-1 expression correlated with elastography-based liver fibrosis (r = 0.35, p = 0.02), whereas P2X7R, P2X4R, NRLP3, Caspase-1, and IL-2 expression correlated with circulating markers of disease severity. P2X7R and P2X4R play a major role in liver inflammation accompanying chronic HCV infection, especially when combined with metabolic damage, while AIM2 is specifically expressed in chronic viral hepatitis. We describe for the first time the hepatic expression of IL-2 in NASH, so far considered a peculiarity of HCV-related liver damage. [ABSTRACT FROM AUTHOR]

The increased resistance of bacteria to antimicrobials, as well as the growing interest in innovative and sustainable alternatives to traditional food additives, are driving research towards the use of natural food preservatives. Among these, hydrolates (HYs) have gained attention as "mild" alternatives to conventional antimicrobial compounds. In this study, the response of L. monocytogenes ATCC 7644 exposed to increasing concentrations of Coridothymus capitatus HY (CHY) for 1 h at 37 °C was evaluated by means of Phenotype Microarray, modelling the kinetic data obtained by inoculating control and treated cells into GEN III microplates, after CHY removal. The results revealed differences concerning the growth dynamics in environmental conditions commonly encountered in food processing environments (different carbon sources, pH 6.0, pH 5.0, 1–8% NaCl). More specifically, for treated cells, the lag phase was extended, the growth rate was slowed down and, in most cases, the maximum concentration was diminished, suggesting the persistence of stress even after CHY removal. Confocal Laser Scanner Microscopy evidenced a diffuse aggregation and suffering of the treated cells, as a response to the stress encountered. In conclusion, the treatment with HY caused a stressing effect that persisted after its removal. The results suggest the potential of CHY application to control L. monocytogenes in food environments. [ABSTRACT FROM AUTHOR]

Bacterial biofilm represents a multicellular community embedded within an extracellular matrix attached to a surface. This lifestyle confers to bacterial cells protection against hostile environments, such as antibiotic treatment and host immune response in case of infections. The Pseudomonas genus is characterised by species producing strong biofilms difficult to be eradicated and by an extraordinary metabolic versatility which may support energy and carbon/nitrogen assimilation under multiple environmental conditions. Nutrient availability can be perceived by a Pseudomonas biofilm which, in turn, readapts its metabolism to finally tune its own formation and dispersion. A growing number of papers is now focusing on the mechanism of nutrient perception as a possible strategy to weaken the biofilm barrier by environmental cues. One of the most important nutrients is amino acid L-arginine, a crucial metabolite sustaining bacterial growth both as a carbon and a nitrogen source. Under low-oxygen conditions, L-arginine may also serve for ATP production, thus allowing bacteria to survive in anaerobic environments. L-arginine has been associated with biofilms, virulence, and antibiotic resistance. L-arginine is also a key precursor of regulatory molecules such as polyamines, whose involvement in biofilm homeostasis is reported. Given the biomedical and biotechnological relevance of biofilm control, the state of the art on the effects mediated by the L-arginine nutrient on biofilm modulation is presented, with a special focus on the Pseudomonas biofilm. Possible biotechnological and biomedical applications are also discussed. [ABSTRACT FROM AUTHOR]

Maize and its derived fermented products, as with other cereals, are fundamental for human nutrition in many countries of the world. Mixed cultures, principally constituted by lactic acid bacteria (LAB) and yeasts, are responsible for maize fermentation, thus increasing its nutritional value and extending the products' shelf-life. Other microorganisms involved, such as molds, acetic acid bacteria, and Bacillus spp. can contribute to the final product characteristics. This review gives an overview of the impact of the activities of this complex microbiota on maize product development and attributes. In particular, starting from amylolytic activity, which is able to increase sugar availability and influence the microbial succession and production of exopolysaccharides, vitamins, and antimicrobial compounds, which improve the nutritional value. Further activities are also considered with positive effects on the safety profile, such as phytates detoxification and mycotoxins reduction. [ABSTRACT FROM AUTHOR]

Despite the enormous potential of nanomedicine, the search for materials from renewable resources that balance bio-medical requirements and engineering aspects is still challenging. This study proposes an easy method to make nanoparticles composed of oxidized starch and chitosan, both isolated from natural biopolymers. The careful adjustment of C/N ratio, polymer concentration and molecular weight allowed for tuning of particle characteristics. The system's carrier capability was assessed both for anti-infectives and for nucleic acid. Higher starch content polyplexes were found to be suitable for high encapsulation efficiency of cationic anti-infectives and preserving their bactericidal function. A cationic carrier was obtained by coating the anionic polyplex with chitosan. Coating allowed for a minimal amount of cationic polymer to be employed and facilitated plasmid DNA loading both within the particle core and on the surface. Transfection studies showed encouraging result, approximately 5% of A549 cells with reporter gene expression. In summary, starch-chitosan complexes are suitable carriers with promising perspectives for pharmaceutical use. [ABSTRACT FROM AUTHOR]

Primary Myelofibrosis (PMF) is a chronic Philadelphia-negative myeloproliferative neoplasm characterized by a skewed megakaryopoiesis and an overproduction of proinflammatory and profibrotic mediators that lead to the development of bone marrow (BM) fibrosis. Since we recently uncovered the upregulation of miR-34a-5p in PMF CD34+ hematopoietic progenitor cells (HPCs), in order to elucidate its role in PMF pathogenesis here we unravelled the effects of miR-34a-5p overexpression in HPCs. We showed that enforced expression of miR-34a-5p partially constrains proliferation and favours the megakaryocyte and monocyte/macrophage commitment of HPCs. Interestingly, we identified lymphoid enhancer-binding factor 1 (LEF1) and nuclear receptor subfamily 4, group A, member 2 (NR4A2) transcripts as miR-34a-5p-targets downregulated after miR-34a-5p overexpression in HPCs as well as in PMF CD34+ cells. Remarkably, the knockdown of NR4A2 in HPCs mimicked the antiproliferative effects of miR-34a-5p overexpression, while the silencing of LEF1 phenocopied the effects of miR-34a-5p overexpression on HPCs lineage choice, by favouring the megakaryocyte and monocyte/macrophage commitment. Collectively our data unravel the role of miR-34a-5p in HPCs fate decision and suggest that the increased expression of miR-34a-5p in PMF HPCs could be important for the skewing of megakaryopoiesis and the production of monocytes, that are key players in BM fibrosis in PMF patients. [ABSTRACT FROM AUTHOR]

Using UAV and multispectral images has contributed to identifying field variability and improving crop management through different data modeling methods. However, knowledge on application of these tools to manage peanut maturity variability is still lacking. Therefore, the objective of this study was to compare and validate linear and multiple linear regression with models using artificial neural networks (ANN) for estimating peanut maturity under irrigated and rainfed conditions. The models were trained (80% dataset) and tested (20% dataset) using results from the 2018 and 2019 growing seasons from irrigated and rainfed fields. In each field, plant reflectance was collected weekly from 90 days after planting using a UAV-mounted multispectral camera. Images were used to develop vegetation indices (VIs). Peanut pods were collected on the same dates as the UAV flights for maturity assessment using the peanut maturity index (PMI). The precision and accuracy of the linear models to estimate PMI using VIs were, in general, greater in irrigated fields with R2 > 0.40 than in rainfed areas, which had a maximum R2 value of 0.21. Multiple linear regressions combining adjusted growing degree days (aGDD) and VIs resulted in decreased RMSE for both irrigated and rainfed conditions and increased R2 in irrigated areas. However, these models did not perform successfully in the test process. On the other hand, ANN models that included VIs and aGDD showed accuracy of R2 = 0.91 in irrigated areas, regardless of using Multilayer Perceptron (MLP; RMSE = 0.062) or Radial Basis Function (RBF; RMSE = 0.065), as well as low tendency (1:1 line). These results indicated that, regardless of the ANN architecture used to predict complex and non-linear variables, peanut maturity can be estimated accurately through models with multiple inputs using VIs and aGDD. Although the accuracy of the MLP or RBF models for irrigated and rainfed areas separately was high, the overall ANN models using both irrigated and rainfed areas can be used to predict peanut maturity with the same precision. [ABSTRACT FROM AUTHOR]

Many biomaterials' surfaces exhibit directional properties, i.e., possess spatial anisotropy on a range of spatial scales spanning from the domain of the naked eye to the sub-micrometer level. Spatial anisotropy of surface can influence the mechanical, physicochemical, and morphological characteristics of the biomaterial, thus affecting its functional behavior in relation, for example, to the host tissue response in regenerative processes, or to the efficacy of spatially organized surface patterns in avoiding bacterial attachment. Despite the importance of the availability of quantitative data, a comprehensive characterization of anisotropic topographies is generally a hard task due to the proliferation of parameters and inherent formal complications. This fact has led so far to excessive simplification that has often prevented researchers from having comparable results. In an attempt to overcome these issues, in this work a systematic and multiscale approach to spatial anisotropy is adopted, based on the determination of only two statistical parameters of surface, namely the texture aspect ratio Str and the roughness exponent H, extracted from atomic force microscopy images of the surface. The validity on this approach is tested on four commercially available implant materials, namely titanium alloy, polyethylene, polyetheretherketone and polyurethane, characterized by textured surfaces obtained after different machining. It is found that the "two parameters" approach is effective in describing the anisotropy changes on surfaces with complex morphology, providing a simple quantitative route for characterization and design of natural and artificial textured surfaces at spatial scales relevant to a wide range of bio-oriented applications. [ABSTRACT FROM AUTHOR]

Previous evidence links the formation of extranuclear inclusions of transcription factors, such as ERK, Jun, TDP-43, and REST, with oxidative, endoplasmic-reticulum, proteasomal, and osmotic stress. To further characterize its extranuclear location, we performed a high-content screening based on confocal microscopy and automatized image analyses of an epithelial cell culture treated with hydrogen peroxide, thapsigargin, epoxomicin, or sorbitol at different concentrations and times to recreate the stresses mentioned above. We also performed a subcellular fractionation of the brain from transgenic mice overexpressing the Q331K-mutated TARDBP, and we analyzed the REST-regulated mRNAs. The results show that these nuclear proteins exhibit a mitochondrial location, together with significant nuclear/extranuclear ratio changes, in a protein and stress-specific manner. The presence of these proteins in enriched mitochondrial fractions in vivo confirmed the results of the image analyses. TDP-43 aggregation was associated with alterations in the mRNA levels of the REST target genes involved in calcium homeostasis, apoptosis, and metabolism. In conclusion, cell stress increased the mitochondrial translocation of nuclear proteins, increasing the chance of proteostasis alterations. Furthermore, TDP-43 aggregation impacts REST target genes, disclosing an exciting interaction between these two transcription factors in neurodegenerative processes. [ABSTRACT FROM AUTHOR]

The picornavirus named 'Ljungan virus' (LV, species Parechovirus B) has been detected in a dozen small mammal species from across Europe, but detailed information on its genetic diversity and host specificity is lacking. Here, we analyze the evolutionary relationships of LV variants circulating in free-living mammal populations by comparing the phylogenetics of the VP1 region (encoding the capsid protein and associated with LV serotype) and the 3Dpol region (encoding the RNA polymerase) from 24 LV RNA-positive animals and a fragment of the 5′ untranslated region (UTR) sequence (used for defining strains) in sympatric small mammals. We define three new VP1 genotypes: two in bank voles (Myodes glareolus) (genotype 8 from Finland, Sweden, France, and Italy, and genotype 9 from France and Italy) and one in field voles (Microtus arvalis) (genotype 7 from Finland). There are several other indications that LV variants are host-specific, at least in parts of their range. Our results suggest that LV evolution is rapid, ongoing and affected by genetic drift, purifying selection, spillover and host evolutionary history. Although recent studies suggest that LV does not have zoonotic potential, its widespread geographical and host distribution in natural populations of well-characterized small mammals could make it useful as a model for studying RNA virus evolution and transmission. [ABSTRACT FROM AUTHOR]

Several wearable devices for physiological and activity monitoring are found on the market, but most of them only allow spot measurements. However, the continuous detection of physiological parameters without any constriction in time or space would be useful in several fields such as healthcare, fitness, and work. This can be achieved with the application of textile technologies for sensorized garments, where the sensors are completely embedded in the fabric. The complete integration of sensors in the fabric leads to several manufacturing techniques that allow dealing with both the technological challenges entailed by the physiological parameters under investigation, and the basic requirements of a garment such as perspiration, washability, and comfort. This review is intended to provide a detailed description of the textile technologies in terms of materials and manufacturing processes employed in the production of sensorized fabrics. The focus is pointed at the technical challenges and the advanced solutions introduced with respect to conventional sensors for recording different physiological parameters, and some interesting textile implementations for the acquisition of biopotentials, respiratory parameters, temperature and sweat are proposed. In the last section, an overview of the main garments on the market is depicted, also exploring some relevant projects under development. [ABSTRACT FROM AUTHOR]

GGDEF-containing proteins respond to different environmental cues to finely modulate cyclic diguanylate (c-di-GMP) levels in time and space, making the allosteric control a distinctive trait of the corresponding proteins. The diguanylate cyclase mechanism is emblematic of this control: two GGDEF domains, each binding one GTP molecule, must dimerize to enter catalysis and yield c-di-GMP. The need for dimerization makes the GGDEF domain an ideal conformational switch in multidomain proteins. A re-evaluation of the kinetic profile of previously characterized GGDEF domains indicated that they are also able to convert GTP to GMP: this unexpected reactivity occurs when conformational issues hamper the cyclase activity. These results create new questions regarding the characterization and engineering of these proteins for in solution or structural studies. [ABSTRACT FROM AUTHOR]

In dairy processing environments, many bacterial species adhere and form biofilms on surfaces and equipment, leading to foodborne illness and food spoilage. Among them, Listeria monocytogenes and Pseudomonas spp. could be present in mixed-species biofilms. This study aimed to evaluate the interactions between L. monocytogenes and P. fluorescens in biofilms simulating dairy processing conditions, as well as the capability of P. fluorescens in co-culture to produce the blue pigment in a Ricotta-based model system. The biofilm-forming capability of single- and mixed-cultures was evaluated on polystyrene (PS) and stainless steel (SS) surfaces at 12 °C for 168 h. The biofilm biomass was measured, the planktonic and sessile cells and the carbohydrates in biofilms were quantified. The biofilms were also observed through Confocal Laser Scanning Microscopy analysis. Results showed that only P. fluorescens was able to form biofilms on PS. Moreover, in dual-species biofilms at the end of the incubation time (168 h at 12 °C), a lower biomass compared to P. fluorescens mono-species was observed on PS. On SS, the biofilm cell population of L. monocytogenes was higher in the dual-species than in mono-species, particularly after 48 h. Carbohydrates quantity in the dual-species system was higher than in mono-species and was revealed also at 168 h. The production of blue pigment by P. fluorescens was revealed both in single- and co-culture after 72 h of incubation (12 °C). This work highlights the interactions between the two species, under the experimental conditions studied in the present research, which can influence biofilm formation (biomass and sessile cells) but not the capability of P. fluorescens to produce blue pigment. [ABSTRACT FROM AUTHOR]

The effect of two kinds of casings on the production and characteristics of a dry fermented sausage was investigated. In detail, an Italian product, naturally fermented at low temperatures and normally wrapped in beef casing instead of the most diffused hog one, was selected. Two different productions (one traditionally in beef casing (MCB) and another in hog casing (MCH)) were investigated over time to determine the differences particularly regarding proteolytic changes during fermentation and ripening. First of all, the product in hog casing required a longer ripening time, up to 120 days, instead of 45–50 days, because of the lower drying rate, while the microbial dynamics were not significantly modified. Conversely, the proteolysis showed a different evolution, being more pronounced, together with the biogenic amines content up to 341 mg/Kg instead of 265 mg/Kg for the traditional products. The latter products were instead characterized by higher quantities of total free amino acids, 3-methyl butanoic acid, 3-Methyl-1-butanal, and 2-Methylpropanal, enriching the final taste and aroma. The traditional product MCB also showed lower hardness and chewiness than MCH. The results highlight how the choice of casing has a relevant impact on the development of the final characteristics of fermented sausages. [ABSTRACT FROM AUTHOR]

The search for novel therapeutics against pulmonary infections, in particular Pseudomonas aeruginosa (PA) biofilm infections, has been intense to deal with the emergent rise of antimicrobial resistance. Despite the numerous achievements in drug discovery and delivery strategies, only a limited number of therapeutics reach the clinic. To allow a timely preclinical development, a formulation should be highly effective, safe, and most importantly facile to produce. Thus, a simple combination of known actives that enhances the therapeutic efficacy would be a preferential choice compared to advanced drug delivery systems. In this study, we propose a novel combination of an anti-inflammatory agent—itaconic acid (itaconate, IA)—and an approved antibiotic—tobramycin (Tob) or ciprofloxacin (Cipro). The combination of Tob and IA at a molar ratio of 1:5 increased the biofilm eradicating efficacy in the strain PA14 wild type (wt) by ~4-fold compared to Tob alone. In contrast, such effect was not observed for the combination of IA with Cipro. Subsequent studies on the influence of IA on bacterial growth, pyocyanin production, and Tob biofilm penetration indicated that complexation with IA enhanced the transport of Tob through the biofilm. We recommend the simple and effective combination of Tob:IA for further testing in advanced preclinical models of PA biofilm infections. [ABSTRACT FROM AUTHOR]

Chitosan coating is a promising method for food preservation. This study aims to fill the data gap regarding the application of chitosan (1% and 2%) on vacuum-packed fresh pork stored at 4 °C for 28 days, with particular attention on the effect on Listeria monocytogenes, inoculated as a cocktail of three strains. Chitosan at both concentrations was able to significantly reduce L. monocytogenes counts by more than 1.5 Log CFU/g with respect to control; moreover, it inhibited the growth of mesophilic bacteria and was particularly effective on lactic acid bacteria and yeasts. The beneficial effects on shelf life were demonstrated by both panel test and pH evolution. In fact, panellists did not detect any sensory difference between samples treated with 1% chitosan and control up to 14 days of storage, while after 28 days, a pungent flesh odour was perceived in control samples only. Interestingly, at aw values of fresh meat (0.984), the chitosan coating exhibited a liquid behaviour, with a dynamic viscosity of 229.4 ± 4.2 mPa/s. Chitosan coating applied on vacuum-packed pork loins contained L. monocytogenes growth and improved the microbiological characteristics of the product, with a beneficial effect on product shelf life. [ABSTRACT FROM AUTHOR]

The diagnosis of psychosis is a challenge for the scientific community, both in terms of its definition and treatment. Some recent studies have investigated the relationship between personality and psychosis onset to prevent or intervene early. Sixty young adults were recruited during their first access in 2019 near the Community Mental Health Service of Niguarda Hospital, Milan, Italy. The assessment included the Social and Occupational Functioning Assessment Scale (SOFAS), the Global Assessment of Functioning (GAF) (clinician scales), the 16-item Version of the Prodromal Questionnaire (PQ-16), the Personality Inventory for DSM-5 (PID-5) (self-report), and a clinical session. Statistical analysis was performed by SPSS. The results show a negative correlation between the Detachment domain and the GAF scores. Correlational analysis also highlights that all PID-5 domains, except for Antagonism, have positive correlations with high scores in the PQ-16. The multivariate analysis of variance showed that patients diagnosed with versus without a psychotic disorder significantly differed on Detachment, Antagonism and Psychoticism PID-5 domains. The involvement of the personality construct in psychopathological development is displayed. In particular, higher levels of Detachment and Psychoticism can distinguish people who are more vulnerable to psychosis or who already have overt psychosis from those who do not have a psychotic predisposition. The study highlights the fundamental role of personality traits, emerging from PID-5, to distinguish young adults at risk of onset.