Integrating nanomaterials like carbon nanotubes (CNTs) and iron oxide (Fe₃O₄) into epoxy composites has significant interest due to their potential to enhance mechanical properties. This study evaluates the impact of dispersion quality on the mechanical performance of CNT/Fe₃O₄/Epoxy composites, comparing stirring and sonication methods at three different loadings: 0.1, 0.3, and 0.5 wt.%. Tensile testing revealed that sonicated composites consistently outperformed stirred composites, with a significant increase in elastic modulus and ultimate tensile strength (UTS). However, fracture strain decreased in both composite types compared to pure epoxy, with sonicated composites experiencing a more significant reduction than stirred composites. These results underscore the importance of high-quality dispersion for optimizing mechanical properties.

This study examines change detection techniques in dense point clouds for the purpose of Cultural Heritage preservation, with a particular focus on the San Pietro Barisano Bell Tower in Matera, Italy. Dense point clouds, obtained via advanced laser scanning, offer detailed 3D representations of heritage structures, facilitating the precise monitoring changes over time. The investigation uses a variety of change detection algorithms, including the Iterative Closest Point (ICP) algorithm, which is renowned for its robust registration capabilities in aligning point clouds with high accuracy. The combination of ICP with deviation analysis and feature-based methods allows for the effective identification of alterations, including deformations, material loss, and surface degradation. This methodology establishes a comprehensive framework for the monitoring of Cultural Heritage, thereby enabling timely and targeted preservation efforts. The results emphasise the substantial contribution of dense point cloud analysis to the enhancement of heritage management and the safeguarding of vulnerable architectural sites.

This work is aimed at showcasing one of the most engaging geoparks in Europe, the Gole della Breggia Geopark. By following its geotrail, the visitors can observe a great deal of features that encompass a wide variety of sedimentary, stratigraphic, tectonic and paleogeographic processes. Its contents are valorized by a comprehensive geotrail that encompasses 23 geostops, enriched with explanatory panels, which enable viewers to gain an overall picture of the complex processes that led to the present-day configuration of the outcrops encountered in the Geopark. We have selected five significative outcrops, which we have regarded as fully-fledged geosites, and which encompass the whole 170-million-year interval, from Early Jurassic to Late Miocene times, during which the rocks of the Geopark were deposited and deformed. We have performed an assessment of the five geosites, using the most common criteria that can be applied for geosite evaluation. The result of the assessment show that the most valuable geosite is the Lombardian Maiolica, highly representative of a pelagic limestone, which is rich in fossil contents, marked by integrity, scien-tific interest and has a major educational value. All geosites, thanks to a QR code added to each figure along the text, can be viewed as Virtual Geosites (VGs), integrated by 360° videos.

In this study electrophoretic deposition (EPD) technique is used to prepare chitosan-based coatings with enhanced antibacterial activity suitable for bone implants applications. We designed, prepared and compared physic-chemical and biological properties of coatings obtained with commercial chitosan, chitosan enriched with silver nanoparticles and chitosan obtained from insects. With the aim to consider the sustainability issue, silver nanoparticles were directly prepared in the chitosan solution by laser ablation in liquid technique, avoiding the use of chemicals and limiting the production of wastes. Moreover, a sustainable source of chitosan such as Hermetia Illucens exuviae was considered. The EPD process was optimized by adjusting parameters like voltage and deposition time to achieve ideal coating thickness and adhesion. The prepared films were characterized by spectroscopic and microscopic techniques such as SEM, XRD, and FTIR. Antimicrobial tests against E. coli and S. aureus revealed that silver nanoparticles enhanced the antibacterial properties of the polymer, whereas biological evaluation using the WST8 test on MG63 human osteoblasts-like cells showed that all coatings are non-toxic. Finally, chitosan obtained from insect showed comparable properties with respect to the commercial polymer, suggesting it could replace seafood-derived chitosan in biomedical applications, whereas the Ag@chitosan composite demonstrated superior antibacterial activity without compromising its biocompatibility.

Digital gait monitoring is increasingly used to assess locomotion and fall risk. The aim of this work is analyzing the changes in the foot-floor contact sequences of Parkinson’s Disease (PD) patients in the year following the implant for deep brain stimulation (DBS). During their best-ON condition, 30 PD patients underwent gait analysis at baseline (T0), at 3 months (T1), and 12 months (T2) after the DBS neurosurgery for bilateral high-frequency subthalamic nucleus stimulation. Thirty age-matched controls underwent gait analysis once. Each subject was equipped with bilateral foot-switches and a 5-minute walk was recorded, including both straight-line and turnings. The walking speed, turning time, stride time variability, percentage of atypical gait cycles, stance, swing, and double support duration were estimated. Overall, the gait performance of PD patients improved after DBS, as also confirmed by the decrease in the UPDRS-III score from 19.4±1.8 to 10.2±1.0 points (T0 vs. T2) (p < 0.001). In particular, the percentage change of atypical gait cycles of PD more affected side decreased at T1 (Straigh-line: -72%; Turnings: -43%) and at T2 (Straigh-line: -54%; Turnings: -20%). The percentage of atypical gait cycles proved an informative digital biomarker for quantifying PD gait changes after DBS, both in straight-line paths and turnings.

The assessment of existing bridges constitutes a serious challenge for the researchers since their safety evaluation is a complex task due to several sources of uncertainty affecting the parameters identified in the knowledge process. In particular, a high level of uncertainties may arise in the case of prestressing systems requiring special investigation strategies and experimental technologies. The paper aims to investigate how the knowledge uncertainties influence the safety assessment of existing post-tensioned bridges. The semi-probabilistic approach is used, and uncertainties related to the knowledge process are described considering the number of tests, the confidence level assumed for the estimation of the problem parameters, and the measurement errors of in-situ tests. Results concerning a typical post-tensioned bridge are reported and the variability of the outcomes is discussed and compared with a reference case of “perfect knowledge”. The main results of the study confirm the general robustness of the semi-probabilistic Eurocodes safety format and provide an overview of dispersion due to different choices about the number of tests and confidence level. The measurement errors may lead to significant under-estimation of the computed structural capacity with respect to the reference one.

Bacillus cereus is a gram-positive bacterium widespread in the environment, especially in soil and dust. It produces two types of toxins causing vomiting and diarrhea. Nowadays, food borne outbreaks due to Bacillus cereus group bacteria (especially Bacillus cereus sensu stricto) are increased, as reported by European Food Safety Authority, representing a very huge problem in agri-food chain. In this work, we analyzed 118 strains belonging to Bacillus cereus group, isolated from several food sources (fruit and vegetables, dairy products, bakery products) concerning their susceptibility to antibiotics currently most used to treat infections. Many strains showing an intermediate susceptibility to clindamycin, erythromycin, and tetracycline were detected, suggesting an evolving acquisition of resistance against these antibiotics. Moreover, one strain showed intermediate resistance to meropenem, another antibiotic currently used to treat infections caused by Bacillus cereus. Beside the antimicrobial characterization, all strains were studied comparing their antimicrobic phenotype with the presence/absence of antimicrobial genes in their genome. The analysis showed a not complete correlation between genes carried by the strains and their phenotype, demonstrating that the antibiotic resistance is due not only to genetic factors, but also to other factors such as the inappropriate use of antibiotics that can determine an acquired resistance for bacteria.

Disease, trauma, and aging account for a significant number of clinical disorders. Regenerative medicine is emerging as a very promising therapeutic option. The design and development of new cell-customized biomaterials able to mimic ECM functionalities represent one of the major strategy to control the cell fate and stimulate tissue regeneration. Recently, hydrogels have received a considerable interest for their use in the modulation and control of cell fate during regeneration processes. Several synthetic bioresponsive hydrogels are being developed in order to facilitate cell-matrix and cell-cell interactions. In this review new strategies and future perspectives of such synthetic cell microenvironment will be highlighted.

Amidst increasing awareness of diet-health relationships, plant-derived bioactive peptides are recognized for their dual nutritional and health benefits. This study investigates bioactive peptides released after Alcalase hydrolysis of protein from chachafruto (Erythrina edulis), a nutrient-rich South American leguminous plant, focusing on their behavior during simulated gastrointestinal digestion. Evaluating their ability to scavenge radicals, mitigate oxidative stress, and influence immune response biomarkers, the study underscores the importance of understanding peptide interactions in digestion. Methods included previous enzymatic hydrolysis with Alcalase to obtain peptides, and results show significant radical scavenging and oxidative stress protection by chachafruto peptides. These findings highlight the potential of chachafruto bioactive peptides in functional foods and nutraceuticals, supporting human health through dietary interventions.

Circulating cell-free DNA (cfDNA) refers to small fragments of DNA molecules released after programmed cell death and necrosis in several body fluids such as blood, saliva, urine, and cerebrospinal fluid. The discovery of cfDNA has revolutionized the field of non-invasive diagnostics in the oncologic field, in prenatal testing, and in organ transplantation. Despite the potential of cfDNA and the solid results published in recent literature, several challenges remain, represented by low abundance, need for highly sensitive assays and analytical issues. In this review, the main technical advances in cfDNA analysis are presented and discussed, with a comprehensive examination of the current available methodologies applied in each field. Considering the potential advantages of cfDNA, this biomarker is increasing its consensus among clinicians, as it consents to monitor patients’ conditions in an easy and non-invasive way, offering a more personalized care. Nevertheless, cfDNA analysis is still considered a research marker to be further validated, and very few centers are implementing its analysis in the real-life assistance. As technical improvements are enhancing the performances of cfDNA analysis, its application will transversally improve patients’ quality of life.

Evaluation of biliary strictures remains a challenge due to the low sensitivity of standard diagnostic work up, but the introduction of direct single-operator cholangioscopy (DSOC) changed this paradigm. Aim of our study was to evaluate diagnostic performance of DSOC and DSOC-targeted biopsies, intraductal ultrasound (IDUS) and brush cytology in patients with indeterminate biliary stricture (IBS). We evaluated patients who underwent advanced diagnostic work up for IBS in our endoscopy unit from ‘01/2018 to ‘12/2022; all patients had at least one previous attempt to characterize the biliary stricture. Final diagnosis was based on surgical pathology and/or clinical and radiological follow-up of at least 12 months. A total of 57 patients with a mean age of 67.2 ± 10.0 years were included, with a mean follow up of 18.2 ± 18.1 months. IBS were mostly located in the distal common bile duct (45.6%) and final diagnosis was consistent with malignancy in 35 patients (61.4%). DSOC and IDUS showed a significantly higher accuracy (89.5% and 82.7% respectively) compared to standard cytology (61.5%, p <0.05). In our experience, DSOC visualization and IDUS both demonstrated an optimal diagnostic yield in the differentiation of IBS, with an acceptable safety profile both quantitatively and qualitatively.

The escalating demand for multifunctional and advanced materials for growing industries has turned scientific exploration to graphene-based hybrid filler polymer composites. The introduction of graphene with other fillers into polymer matrices results in astonishing properties and thus has gained significant attention in recent years. This study addresses the significance of graphene-based hybrid filler polymer composites in progressive materials science and engineering. The paper encloses some traditional and current preparation techniques employed in the fabrication of composites and a comprehensive review of successfully prepared graphene hybrid polymer composites with enhanced mechanical, thermal, and electrical properties reported in published research. The role of different factors, e.g., filler type, aspect ratios, filler-matrix compatibility, dispersion effects, homogeneity, filler orientation through polymer matrices, and curing conditions, are summarized. Finally, the applications in heavy industries, e.g., aerospace, electronics, energy storage, and automotive sectors were also analyzed. We hope this study will serve as a practical resource for new researchers and practitioners to understand and harness the full potential of these composites in various scientific and industrial fields.

Environmental contamination has exposed humans to various metal agents, including mercury. It has been determined that mercury is not only harmful to the health of vulnerable populations such as pregnant women and children, but is also toxic to ordinary adults in various ways. For many years, mercury was used in a wide variety of human activities. Nowadays, the exposure to this metal from both natural and artificial sources is significantly increasing. Recent studies suggest that chronic exposure, even to low concentration levels of mercury, can cause cardiovascular, reproductive and developmental toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, and carcinogenicity. Possible biological effects of mercury, including the relationship between mercury toxicity and diseases of the cardiovascular system, such as hypertension, coronary heart disease and myocardial infarction, are being studied. As heart rhythm and function are under autonomic nervous system control, it has been hypothesized that the neurotoxic effects of mercury might also impact cardiac autonomic function. Mercury exposure could have a long-lasting effect on cardiac parasympathetic activity and some evidence show that mercury exposure might affect heart rate variability, particularly early exposures in children. The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. The exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system.

In this study the effects of three different main preparatory tillage operations [ploughing at 0.4 m (P40) and 0.20 m (P20) depth and minimum tillage at 0.20 m depth (MT) each of them carried out at two different soil water contents (WC) [low, 58% (LH) and high, 80% (HH) of field capacity] were investigated. The results obtained in this research show high values of soil strength in term of Penetration resistance (CI) and shear strength (SS) particularly in deeper soil layers at lower water content. Fossil-fuel energy requirements both for P40 LH and P20 LH were 25 and 35% higher with respect to the HH treatments and tractor slip were very high (P40 LH = 32.4%) with respect to the P40 HH treatment (16%). Therefore soil water content had significantly influenced tractor performance during soil ploughing, particularly at 0.40 m depth while MT was not influenced at all. A significant correlation between grain yield and soil penetration resistance was found highlighting how soil strength may be good indicator of its productivity. Obtained results during these field tests allowed considering MT and P20 treatments more suitable for this type of soil in climate change scenarios.

Recently Candida auris has emerged as a multi-resistant fungal pathogen, with a significant clinical impact, and has become a critical issue in WHO fungal priority list, due to its unique ability to persist for long time on human skin and hospital environments. It is therefore fundamental to reinforce hospital surveillance protocols to limit nosocomial outbreaks. The study purpose was the Fourier-Transform Infrared Spectroscopy (FT-IR) application to investigate the phylogenetic relationships between isolated strains within the C. auris outbreak at the university Intensive Care Unit of a Tertiary University hospital in Turin (Italy). In order to calculate a clustering cut-off, intra- and inter-isolates distance values were analysed. Data showed the presence of a major cluster Alfa and a minor cluster Beta with a defined C. auris clustering cut-off. The results were validated by an external C. auris strain and Principal Component and Linear Discriminant Analysis. The application of FT-IR technology had allowed to obtain important information about the phylogenetic relationships between the analysed strains, defining for the first time a “not WGS-based” clustering cut-off with a statistical-mathematical approach. FT-IR could represent a valid alternative to molecular methods for rapid and cost saving typing of C. auris strains with important clinical implications.

Chiroptera includes of over 1,400 bat species with at least 35 of these present in Italy. Due to their role as lyssavirus reservoirs, in Italy, dead bats and oral swabs are routinely submitted to the laboratory network of the Istituti Zooprofilattici Sperimentali within in the framework of the rabies national passive and active surveillance programme. Carcasses and biological samples collected from January to December 2021 in Latium and Tuscany Regions were further screened for the presence of Coronaviruses (CoVs) and Herpesviruses, using pan-family virus PCR tests and relative PCR products were Sanger sequenced. Subsequent to the viral investigations, genetic bat species was also carried out. Viral characterization detected AlphaCoVs in Miniopterus schreibersii and Beta- and Gamma-Herpesviruses in Tadarida Teniotis.

Over the past thirty years, the red gorgonian Paramuricea clavata in the Mediterranean Sea has faced increasing threats, including heat waves and human activities such as fishing and diving. Epibiosis on damaged gorgonian colonies is generally used as an indirect indication of stressed conditions. The density and height of P. clavata and the percentage of colonies affected by epibiosis and entangled in lost fishing gear were studied to investigate the phenomenon and its trend over time in the Ligurian Sea. Analyses were based on transects collected during ROV campaigns between 2015 and 2022 at depths of 33-90 meters. A strong correlation was observed between fishing effort in the study area and the level of epibiosis. Maximal percentages of colonies affected by epibiosis and entanglement were recorded at depths of 50-70 meters. Temporally, marine heat waves before 2019 were identified as the primary cause of damage to P. clavata. The decrease in epibiosis percentages after 2019, despite the 2022 heat wave, may be due to a quick recovery ability of the populations and a reduction in fishing activities during the COVID-19 lockdown in 2020. Long-term monitoring programs are essential to understand the changes in marine benthic communities exposed to different stressors.

Background: Skin- (SSM) and nipple-sparing (NSM) mastectomies are frequently performed surgeries with a considerable risk for post-operative hematoma or seroma. Tranexamic acid (TXA) is a potent antifibrinolytic drug commonly used in many surgical fields but rather novel in plastic and specifically breast surgery. This study investigates the influence of TXA in patients undergoing SSM or NSM with expander-based reconstruction (EbR) on post-operative outcomes. Methodology: A retrospective study was conducted on 132 patients undergoing uni- or bilateral SSM or NSM with EbR between May 2015 and March 2022. Patients receiving systemic TXA treatment for 48 hours following a standardized protocol were compared to those who received no treatment. Multivariable linear regression was performed to identify influencing factors and quantify their effect on drainage volume, duration of drain placement, length of hospital stay, post-operative bleeding, and seroma formation. Results: 132 patients underwent a total of 155 mastectomies (72 in the TXA group, 83 in the control group). TXA significantly reduced drainage volume (-22.3ml, P=0.011). Duration of drain placement and length of hospital stay were significantly shorter in the TXA group (P&lt;0.001 and P=0.001). No significant side effects were reported. Conclusion: TXA is a safe drug if administered respecting the well-defined contraindications. Systemic TXA administration significantly reduces drainage volume in patients undergoing SSM or NSM and should encourage surgeons to reconsider using drains in post-operative protocols. Duration of drain placement and length of hospital stay were significantly reduced in the TXA group but other factors like resection weight might have a more substantial impact.

Graphene hybrid-filler polymer composites have emerged as prominent materials that revolutionize heavy industries. This study encapsulates the in-depth analysis of different influential factors such as filler/graphene type, aspect ratios, dispersion methods, filler-matrix compatibility, fiber orientation, synergistic effects, different processing techniques, and post-curing conditions that affect the processing, properties and determine the resultant applications of graphene hybrid polymer composites. Additionally, it discusses the substantial role of graphene collaboration with other fillers such as carbon nanotubes, silica, nano-clays and metal oxides to produce functionalized hybrid polymer composites with synergistically enhanced tailored properties to offer solutions for heavy industries like aerospace, automotive, electronics, and energy harvesting. The review concludes with some suggestions and outlook on the future of these composite materials by emphasizing the need for continued research to fully optimize their potential.

In recent years, there has been an intensification of weather variability worldwide as a result of climate change. Some regions have been affected by drought, while others have experienced more intense rainfall. The incidence and severity of mouldy grain and mycotoxin contamination during the growing and harvesting seasons have increased as a result of these weather conditions. Addi-tionally, torrential rains and wet conditions may cause delays in grain drying, leading to mold growth in the field. In July 2023, a wheat field in Lecco (Lombardy, Italy) was affected by torren-tial rains that led to the development of the Claviceps fungi. In the field, dark sclerotia were identi-fied on some ears. Wheat ears, kernels and sclerotia were collected and analyzed by LC-MS/MS at IZSLER, Food Chemical Department, in Bologna. The wheat ears, kernels and sclerotia were ana-lyzed for 12 ergot alkaloids (EAs) according to (EU) Regulation 2023/915 (er-gocornine/ergocorninine; ergocristine/ergocristinine; ergocryptine/ergocryptinine; ergome-trine/ergometrinine; ergosine/ergosinine; ergotamine/ergotaminine), after QuEChERS (Z-Sep/C18) purification. The analyzed sclerotia showed significant differences in total alkaloids content that varies between 0.01-0.5% (w/w), according to the results of 2017 EFSA scientific report. EAs de-tected in sclerotia were up to 4951 mg/kg, in wheat ears up to 33 mg/kg, and in kernels were 1 mg/kg. Additional mycotoxins including ochratoxin A, deoxynivalenol, zearalenone, fumonisins, T2-HT2 toxins, and aflatoxins were investigated in wheat kernels, after purification with immu-noaffinity columns (IAC). The analysis revealed the presence of deoxynivalenol in wheat kernels at a concentration of 2251 µg/kg. It is expected that climate change will increase the frequency of extreme weather events. In order to mitigate the potential risks associated with mycotox-in-producing fungi and to ensure the protection of human health, it is suggested to implement of-ficial controls in the field.

The onset of neurodegenerative diseases involves a complex interplay of pathological mecha-nisms, including protein aggregation, oxidative stress, impaired autophagy. This review focuses on the intricate connection between oxidative stress and autophagy in neurodegenerative disor-ders, highlighting autophagy as pivotal in disease pathogenesis. Reactive oxygen species (ROS) play dual roles in cellular homeostasis and autophagy regulation, with disruptions of redox sig-naling contributing to neurodegeneration. The activation of the Nrf2 pathway represents a criti-cal antioxidant mechanism, while autophagy maintains cellular homeostasis by degrading al-tered cell components. The interaction between p62/SQSTM1, Nrf2 and Keap1 forms a regulatory pathway essential for cellular stress response, whose dysregulation leads to impaired autophagy and aggregate accumulation. Targeting the Nrf2-p62/SQSTM1 pathway holds promise for thera-peutic intervention, mitigating oxidative stress and preserving cellular functions. Additionally, the review explores the potential synergy between the endocannabinoid system and Nrf2 signal-ing for neuroprotection. Further research is needed to elucidate the involved molecular mecha-nisms and develop effective therapeutic strategies against neurodegeneration.

The paper, through and extended literature review, based on bibliometrics and conceptual reasoning, analyzes the main models of coopetition, in order to verify the link between coopetition and innovation, getting to proposal that can be useful for further research.

Automatic Milking Systems (AMS) are revolutionizing the dairy industry by boosting herd effi-ciency, primarily through increased milk yield per cow and reduced labor costs. The performance of milking machines, whether traditional or automated, can be evaluated using advanced vacuum meters through dynamic testing. This process involves scrutinizing the system and milking rou-tine to identify critical points, utilizing the VaDia™ logger (BioControl AS, Rakkestad, NO). Vacuum recordings were downloaded and analyzed using the VaDia Suite™ software under the guidance of a milking specialist. Access to data from AMS across various manufacturers and herds facilitated a retrospective study aimed at describing and comparing key milk emission parameters for different AMS brands while identifying potential mastitis risk factors. Using proper statistical procedures of SPSS 29.1 (IBM Corp, USA), researchers analyzed data from 4,878 individual quarter milkings from cows in 48 dairy herds. Results indicated significant variability in milking pa-rameters associated to quarter milk yield and AMS brand. Notably, despite AMS standardizing teat preparation and stimulation, the study revealed a surprisingly high frequency of two major mastitis risk factors—bimodality and irregular vacuum fluctuations—occurring more frequently than in conventional milking systems. This study, one of the few comparing different AMS brands and their performance, highlights the crucial role of dynamic testing in evaluating AMS perfor-mance under real-world conditions.

The demand for polymer composites with improved mechanical and electrical properties is crucial for advanced aerospace, electronics, and energy storage applications. Single-walled carbon nanotubes (SWCNTs) and iron oxide (Fe₃O₄) nanoparticles are key fillers that enhance these properties, yet challenges like orientation, uniform dispersion, and agglomeration must be addressed to realize their full potential. This study focuses on developing SWCNTs/Fe₃O₄ epoxy composites by keeping the SWCNT concentration constant at 0.03 Vol.% and varying Fe₃O₄ concentrations at 0.1, 0.5, and 1 Vol.% with two different configurations: randomly orientated (R-) and magnetic field-assisted horizontally aligned (A-) SWCNTs/Fe3O4 epoxy composites and investigates the effects of filler concentration, dispersion, and magnetic alignment on the mechanical and electrical properties. The research reveals that both composite configurations achieve an optimal mechanical performance at 0.5 Vol.% Fe₃O₄, while A- SWCNTs/Fe3O4 epoxy composites outperformed at all concentrations. However, at 1 Vol.% Fe₃O₄, mechanical properties decline due to nanoparticle agglomeration, which disrupts stress distribution. In contrast, electrical conductivity peaks at 1 Vol.% Fe₃O₄, indicating that the higher density of Fe₃O₄ nanoparticles enhances the conductive network despite the mechanical losses. This study highlights the need for precise control over filler content and alignment to optimize mechanical strength and electrical conductivity in SWCNTs/Fe₃O₄ epoxy nanocomposites.

How hematopoietic stem and progenitor cell (HSPC) fate decisions are affected by genetic alterations acquired during AML leukemogenesis is poorly understood and mainly explored in animal models. Here, we studied isocitrate dehydrogenases (IDH) genes mutations in the human model of HSPC and provide a review of the literature on this topic. IDH1/2 mutations occur in ~20% of AML, are recognized among the mutations earliest acquired during leukemogenesis, and are target of specific inhibitors (ivosidenib and enasidenib, respectively). In order to investigate the direct effects of these mutations on the HSPC we expressed by lentiviral transduction either IDH1-R132H or IDH2-R140Q mutants into human CD34+ healthy donor cells and analyzed the colony-forming unit (CFU) ability. CFU ability was dramatically compromised with a complete trilineage block of differentiation. Strikingly, the block was reversed by the specific inhibitors, confirming it was a specific effect induced by the mutants. In line with this observation, the CD34+ leukemic precursors isolated from a patient with IDH2-mutated AML at baseline and during enasidenib treatment showed over time a progressive and marked improvement of their fitness in terms of CFU ability and propensity to differentiate, attaining clonal trilinear reconstitution of hematopoiesis and complete hematological remission.

A comprehensive study of the interactions of human serum albumin (HSA) and α-1-acid glycoprotein (AAG) with two isoquinoline alkaloids: allocryptopine (ACP) and protopine (PP) was performed. The UV-Vis spectroscopy, molecular docking, competitive binding assays, and circular dichroism (CD) spectroscopy were used for the investigations. The results showed that ACP and PP form spontaneous and stable complexes with HSA and AAG, with ACP displaying a stronger affinity towards both proteins. Molecular docking studies showed also revealed the preferential binding of ACP and PP to specific sites within HSA, with site 2 (IIIA) being identified as the favored location for both alkaloids. This was supported by competitive binding assays using markers specific to HSA's drug binding sites. Similarly, for AAG, a decrease in fluorescence intensity upon addition of the alkaloids to AAG/ Quinaldine Red (QR) complexes indicated the replacement of the marker by the alkaloids, with ACP showing a greater extent of replacement than PP. CD spectroscopy showed that the proteins’ structures remained largely unchanged suggesting that the formation of complexes did not significantly perturb the overall spatial configuration of these macromolecules. These findings are crucial for advancing the knowledge on the natural products-protein interactions and the future design of isoquinoline alkaloid-based therapeutics.

The mechanisms of the innate immunity control on equine infectious anaemia virus in asymptomatic horses are not yet widely described. Horse monocytes from peripheral blood can be differentiated in vitro into macrophages, that generally gives rise to mixed populations, morphologically referable to M1 and M2. The addition of specific cytokines or of virus, results in a more specific differentiation. As stated for other species (Crespo et al, 2013), stimulation with equine recombinant cytokine IFNγ polarized horse macrophages towards the M1 phenotype while equine recombinant cytokine IL4 polarized towards the M2 phenotype. EIAV Wyoming and Miami strains infection resulted in morphological transformation of macrophages compatible with the M1 pattern of differentiation. In this study MMP13 represented a reliable target gene to evaluate proinflammatory status of macrophages in horses since IFNγ and EIAV infection considerably increased its expression. A more in-depth study of the expression genes of both cytokine-induced and virus-induced markers of eMDM polarization may help us to understand whether these are the same in the horse as those found in other animal species with similar modes of activation of innate immunity. The identification of the markers of each population of macrophages would allow to analyze the differentiation profiles, and to check the control of virus infectivity in equid populations envisioning therapeutic strategies through the use of this information.

Background Cervical insufficiency, marked by recurrent painless cervix dilation leading to second-trimester pregnancy losses, is traditionally managed through cerclage placement and vaginal progesterone administration. However, a recent experimental approach targeted intra-amniotic inflammation or infection in a selected group of women with cervical dilation over 1 cm, intact membranes, and no uterine contractions in the second or third trimester. Case presentation We report a case of a 21 year old primigravid woman who experienced resolution of mid-trimester cervical insufficiency after the administration of triple antibiotic therapy, as confirmed by ultrasound monitoring. Remarkably, the patient successfully carried the pregnancy to term and delivered a healthy baby. Conclusions This case highlights the potential effectiveness of a novel combination of antibiotics, even in the presence of several high-risk pregnancy conditions, and underscores the possibility of a favorable outcome.

Capturing atmospheric CO2 and storing it in natural rock systems (i.e., alkaline earth silicate and hydroxide minerals) through carbonation reactions is a promising greenhouse gas mitigation research, and largely depends on the use of hydrated ultramafic rocks (serpentinites), which are widespread in orogenic belts around the globe. The Jurassic ophiolites in the Southern Apennines represent a natural analogue and a great opportunity for the mineralogical sequestration of CO2. Serpentinites of the Pollino ophiolite Massif have been widely studied for their mineralogical, petrographic, and chemical characteristics, providing major findings on their impact on environmental and human health issues. Serpentinites here have been divided into cataclastic and massive types based on their structures and are characterized by pseudomorphic and vein textures. The mineralogy of the studied serpentinites consists of lizardite, antigorite, clino-crysotile, Cr-chlorite, magnetite, tremolite, actinolite, pyroxene and calcite, and the most commonly occurring serpentine minerals are polymorphs of serpentine including lizardite, clino-crysotile and antigorite. Systematic petrographic and mineralogical studies of serpentinites in ophiolites, such as those outcropping in the Southern Apennines can represent a starting point for the study of natural materials, which can be used for CO2 storage and sequestration. A particular attention must be given to those carbonate phases, produced by carbonation processes to check whether the serpentinites of the Pollino Massif can be used for the induced mineral Carbon Capture Storage (CCS). If successful, this technique and the Pollino Massif serpentinites can become highly significant in safeguarding the health of our planet's climate.

Metallo-β-lactamases (MBLs) are members of the structurally conserved but functionally diverse MBL-fold superfamily of metallohydrolases. MBLs are a major concern for global health care as they efficiently inactivate β-lactam antibiotics, including the “last-resort” carbapenems, and no clinically suitable inhibitors are currently available. Increasingly, promiscuous β-lactamase activity is also observed in other members of the superfamily, including from viruses, which represents an underexplored reservoir for future pathways to antibiotic resistance. Here, two such MBL-fold enzymes from Bacillus phages, the cyclic mononucleotide-degrading proteins ApycGoe3 and ApycGrass, are shown to efficiently degrade β-lactam substrates in vitro. In particular, ApycGrass displays a distinct preference for carbapenem substrates with a catalytic efficiency that is within one order of magnitude of that of the clinically relevant MBL NDM-1. Mutagenesis experiments also demonstrate that the loss of a metal-bridging aspartate residue reduces nuclease activity up to 35-fold, but improves carbapenemase activity. In addition, we propose that the oligomeric state significantly influences β-lactamase activity by modifying access to the active site pocket. Together, these observations hint at a possible new avenue of resistance via the spread of phage-borne MBL-fold enzymes with β-lactamase activity.

Staphylococcus aureus mastitis remains a major challenge for dairy farming. Here, 24 mice were immunized and divided into four groups: G1: control; G2: Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) DNA vaccine; G3: F0F1 ATP synthase subunit α (SAS), succinyl-diaminopimelate (SDD), and cysteinyl-tRNA synthetase (CTS) recombinant proteins; and G4: SAS+SDD+CTS plus GM-CSF DNA vaccine. The lymphocyte subpopulations and the intracellular interleukin-17A (IL-17A) and interferon-γ production in the draining lymph node cells were immunophenotyped by flow cytometry. The immunophenotyping and lymphocyte proliferation was determined in spleen cells cultured with and without S. aureus stimulus. Immunization with S. aureus recombinant proteins generated memory cells in draining lymph nodes. Immunization with the three recombinant proteins plus GM-CSF DNA led to an increase in the percentage of IL-17A+ cells among overall CD44+ (memory), T CD4+, CD4+ T CD44+ CD27-, γδ TCR, γδ TCR+ CD44+ CD27+ and TCRVγ4+ cells. Vaccination with S. aureus recombinant proteins associated with GM-CSF DNA vaccine downregulates TH2 immunity. Immunization with the three recombinant proteins plus the GM-CSF DNA led to a proliferation of overall memory T, CD4+ and CD4+ TEM cells upon S. aureus stimulus. This approach fostered type 3 immunity, suggesting the development of a protective immune response against S. aureus.

The occurrence and abundance of Astrospartus mediterraneus (Risso, 1826) have significantly increased in the last three decades in several areas of the Mediterranean Sea. In the Tavolara – Punta Coda Cavallo Marine Protected Area (NE Sardinia, Tyrrhenian Sea), 61 specimens were observed mainly on the granitic shoals of the Tavolara Channel, an area characterized by very intense currents and high sedimentation. The basket stars were mainly found living as epibionts of gorgonians (E. verrucosa, P. clavata and L. sarmentosa) and massive sponges (Spongia officinalis, S. lamella, Sarcotragus foetidus). We also documented 20 small specimens (3-20 mm in diameter of the oral disc) observed in June 2024 between 27 and 52 m depth on Eunicella verrucosa and Paramuricea clavata colonies. The bimodal size-frequency distribution of these specimens suggested that, probably, specimens belong to two different reproductive events occurring in spring 2023 and 2024.

The rationalization of single molecule magnets’ (SMMs) magnetic properties by quantum mechanical approaches represents a major task in the field of the Molecular Magnetism. The fundamental interpretative key of molecular magnetism is the phenomenological Spin Hamiltonian and the understanding of the role of its different terms by electronic structure calculations is expected to steer the rational design of new and more performing SMMs. This paper deals with the ab initio calculation of isotropic and anisotropic exchange contributions in the Fe(III) dimer [Fe₂(OCH₃)₂(dbm)₄]. This system represents the building block of one of the most studied Single Molecule Magnets ([Fe₄RC(CH₂O)₃)₂(dpm)₆] where R can be an aliphatic chain or a phenyl group just to name the most common functionalization groups) and its relatively reduced size allows the use of a high computational level of theory. Calculations were performed using CASSCF and NEVPT2 approaches on the X-ray geometry as assessment of the computational protocol, which has then be used to evinced the importance of the outer coordination shell nature through organic ligand modelization. Magneto-structural correlations as function of internal degrees of freedom for isotropic and anisotropic exchange contributions are also presented, outlining for the first time the extremely rapidly changing nature of the anisotropic exchange coupling.

Breast cancer (BC) is the most common invasive neoplasm and affects many women of working age. The return to work (RTW) of female survivors (BCSs) is associated with a better quality of life and longer survival. A tailored intervention to promote RTW was launched in 2022. A year later, the women were contacted to find out if RTW had occurred regularly and what their health conditions were compared to baseline. BCSs reported excessive fatigue, poor sleep quality, anxiety, depression and reduced work ability; these parameters had not improved significantly compared to baseline. Thematic analysis of the interviews confirmed the presence of personal, company and societal factors that could hinder or favor RTW. The interviews demonstrated that, even in an economically developed country that has provided numerous benefits for BCSs, protection is not always effective. Personalized intervention seems necessary to complete the process of reintegrating BCSs into their future working careers.

Spider silks, renowned for their exceptional mechanical and biocompatible properties, offer significant potential as scaffolds in tissue engineering. This paper explores the feasibility of using spidroins, the primary proteins in spider silk, to develop scaffolds that closely mimic the extracellular matrix (ECM) essential for tissue regeneration. Spidroins (spider silk proteins) are particularly valuable due to their unique strength, elasticity, and biocompatibility, which support cellular growth and differentiation. The paper examines current methods for producing recombinant spider silk, including using unicellular hosts like E. coli and multicellular systems like transgenic plants and silkworms. It also examines current scaffolds that utilize spidroins and their shortcomings, such as immunogenicity and protein production, which must be urgently addressed for more practical and effective widespread biomedical applications. In addition, it stresses the need for further research to solve these challenges and fully realize the potential of spider silk in biomedical applications.

Analysis of liquid biopsy samples can reveal a wealth of molecular as well as cellular entities circulating in various body fluids. These entities include circulating tumor cells, circulating cell-free and tumor DNA, RNA, and proteins. Detection and characterization of this genetic and proteomic material can provide crucial information on tumor characteristics, including its heterogeneity, biology, tumor progression, staging, associated gene mutations and the course of therapy. The increased use of liquid biopsy in clinical oncology offers in non-invasive manner easier tumor sampling and continuous monitoring of the disease evolution through repetitive sampling from cancer patients. The continuous monitoring offered by this method is highly relevant to the assessment of a given therapeutic regime and early detection of markers associated with possible drug resistance, which may develop in the course of the therapy. The use of proteomic approaches, including mass spectrometry-based proteomics for the analysis of biofluids extends for over three decades, yet only in the last few years such methods have found their way to clinical oncology. The non-invasive nature of liquid biopsy and the simple procedures for sample collection made this approach far more attractive than the traditional and well-established tissue biopsy. Such preference becomes more practical in the analysis of solid tumors, particularly in pediatric population. In this review we discuss some works on the emerging role of liquid biopsy analyses in clinical oncology, and how such use allows a better understanding of diagnosis, prognosis, disease evolution and response to therapy of various forms of cancer. We also discuss the role of MS-based methods in the characterization of post-translational modifications of proteins circulating in liquid biopsies.

A distinction is made between data rescue (i.e., copying, digitizing and archiving) and data recovery that implies deciphering, interpreting and transforming early instrumental readings and their metadata to obtain high-quality datasets in modern units. This requires a multidisciplinary approach that includes: palaeography and knowledge of Latin and other languages to read the handwritten logs and additional documents; history of science to interpret the original text, data e metadata within the cultural frame of the 17th, 18th and early 19th century; physics and technology to recognize bias of early instruments or calibrations, or to correct for observational bias; astronomy to calculate and transform the original time in canonical hours that started from twilight. The liquid-in-glass thermometer was invented in 1641 and the earliest temperature records started in 1654. Since then, different types of thermometers were invented, based on the thermal expansion of air or selected thermometric liquids with deviation from linearity. Reference points, thermometric scales, calibration methodologies were not comparable, and not always adequately described. Thermometers had various locations and exposures, e.g., indoor, outdoor, on windows, gardens or roofs, facing different directions. Readings were made only one or a few times a day, not necessarily respecting a precise time schedule: this bias is analysed for the most popular combinations of reading times. The time was based on sundials and local Sun, but the hours were counted starting from twilight. In 1789-90 Italy changed system and all cities counted hours from their lower culmination (i.e., local midnight), so that every city had its local time; in 1866, all the Italian cities followed the local time of Rome; in 1893, the whole Italy adopted the present-day system, based on the Coordinated Universal Time and the time zones. In 1873, when the International Meteorological Committee (IMO) was founded, later transformed in World Meteorological Organization (WMO), a standardization of instruments and observational protocols was established, and all data became fully comparable. In the early instrumental period, from 1654 to 1873, the comparison, correction and homogenization of records is quite difficult, mainly because of the scarcity or even absence of metadata. This paper deals about this confused situation, discussing the main problems, but also the methodologies to recognize missing metadata, distinguish indoor from outdoor readings; correct and transform early datasets in unknown or arbitrary units into modern units; finally, in which cases it is possible to reach the quality level required by WMO. The focus is to explain the methodology needed to recover early instrumental records, i.e., the operations that should be performed to interpret, correct, and transform the original raw data into a high-quality dataset of temperature, usable for climate studies.

Background: Malnutrition commonly affects patients with oral squamous cell carcinoma (OSCC), which contributes to worsening prognosis. Moreover, specific strategies for diagnosing and managing malnutrition in OSCC are lacking. Methods: This retrospective study included 52 consecutive patients with OSCC who underwent surgery at the University Hospital of Palermo (I) from Jan 2020 to May 2023. In-hospital nutritional support was provided by a dedicated team. The patients were compared with a historical control group of 11 patients. The nutritional treatment consisted of standard oral (ON) or artificial nutrition (AN). Traditional measurements, including bioimpedance-derived body composition and volumetric reconstruction of the posterior paraspinal muscles at the C3 level based on magnetic resonance imaging (MRI-C3), were obtained in 16 patients to investigate sarcopenia. Results: The patients were categorized according to TNM stage: groups A (TNM stages I-III) and B (IVa-IVc). The prevalence of group A patients was 59.6% in the case group and 90.9% in the control group (P

Densely urbanized areas, with a low percentage of green vegetation, are highly exposed to Heat Waves (HW) which nowadays are increasing in terms of frequency and intensity also in the middle-latitude regions, due to ongoing Climate Change (CC). Their negative effects may combine with those of the UHI (Urban Heat Island), a local phenomenon where air temperatures in the compact built up cores of towns increase more than those in the surrounding rural areas, with significant impact on the quality of urban environment, on citizens health and energy consumption and transport, as it has occurred in the summer of 2003 on France and Italian central-northern areas. In this context this work aims at designing and developing a methodology based on aero-spatial remote sensing (EO) at medium-high resolution and most recent GIS techniques, for the extensive characterization of the urban fabric response to these climatic impacts related to the temperature within the general framework of supporting local and national strategies and policies of adaptation to CC. Due to its extension and variety of built-up typologies, the municipality of Rome was selected as test area for the methodology development and validation. First of all, we started by operating through photointerpretation of cartography at detailed scale (CTR 1: 5000) on a reference area consisting of a transect of about 5x20 km, extending from the downtown to the suburbs and including all the built-up classes of interest. The reference built-up vulnerability classes found inside the transect were then exploited as training areas to classify the entire territory of Rome municipality. To this end, the satellite EO HR (High Resolution) multispectral data, provided by the Landsat sensors were used within a on purpose developed "supervised" classification procedure, based on data mining and “object-classification” techniques. The classification results were then exploited for implementing a calibration method, based on a typical UHI temperature distribution, derived from MODIS satellite sensor LST (Land Surface Temperature) data of the summer 2003, to obtain an analytical expression of the vulnerability model, previously introduced on a semi-empirical basis.

Menin inhibitors are new and promising agents currently in clinical development that target the HOXA/MEIS1 transcriptional program which is critical for leukemogenesis in histone-lysine N-methyltransferase 2A rearranged (KMT2Ar) and in NPM1-mutated (NPM1mut) acute leukemia. The mechanism of action of this new class of agents is based on the disruption of menin-KMT2A complex (constitute of chromatin remodelling proteins), leading to the differentiation and apoptosis of AML cells expressing KMT2A or mutated NPM1. This new class of drugs has been tested alone, or in combination with synergistic drugs, in phase I and II clinical trials (AUGMENT-01 and 02, KOMET-01 and 07, SAVE, COVALENT trial and others), showing promising results in terms of response rates and safety in heavily pre-treated acute leukemia patients. In this review, we summarise the key findings on menin inhibitors, focusing on the mechanism of action and preliminary clinical data of this emerging and promising class of agents, in particular revumenib and ziftomenib.

Equine hepacivirus (EqHV, Flaviviridae, Hepacivirus) is a small, enveloped, RNA virus generally causing sub-clinical hepatitis with occasional fatalities. EqHV is reported in equids worldwide, but for Italy data are limited. To address this, a survey study was set up to estimate prevalence at national level and among different production categories (equestrian, competition, work and meat and reproduction) and national macro-regions (North, Central, South and Islands). Data obtained testing 1801 horse serum samples by Real-Time RT PCR were compared within the categories and regions. The NS3 fragment of the PCR-positive samples was sequenced by Sanger protocol for phylogenetic and mutational analysis. The tertiary structure of the NS3 protein was also assessed. The estimated national prevalence was 4.27% [1.97-6.59, 95%CI] and no statistical differences were detected among production categories and macro-regions. The phylogenesis confirmed the distribution in Italy of the three known EqHV subtypes, suggesting also a possible fourth sub-type that however requires further confirmation. Mutational profiles that could also affect the NS3 binding affinity to the viral RNA were detected. The present paper demonstrates that EqHV should be included in diagnostic protocols when investigating causes of hepatitis and in quality control protocols for blood derived products, due to its parental transmission.

The spread of high-performance personal computers, frequently equipped with powerful Graphic Processing Units (GPU), raised the interest on a set of techniques able to extract models of electromagnetic phenomena (and devices) directly from available examples of the desired behavior. Such approaches are collectively referred to as Machine Learning (ML). A typical representative ML approach is the so called “Neural Network” (NN). Using such data-driven models allows evaluating the output in a much shorter time when a theoretical model is available, or allows predicting the behavior of the systems and devices when no theoretical model is available. With reference to a simple yet representative benchmark electromagnetic problem, some of the possibilities and the pitfalls of the use of NN for the interpretation of measurements (inverse problem) or to obtain the required measurements (optimal design problem) are discussed. The investigated aspects include the choice of the NN model; the generation of the dataset(s); the selection of hyperparameters (hidden layers, training paradigm). Finally, the capabilities in the handling of ill-posed problems are critically revised.

Digital Twin (DT) technology is a pivotal innovation within the built environment industry, facilitating digital transformation through advanced data integration and analytics. DTs have demonstrated significant benefits in building design, construction, and asset management, including optimizing lifecycle energy use, enhancing operational efficiency, enabling predictive maintenance, and improving user adaptability. By integrating real-time data from IoT sensors with advanced analytics, DTs provide dynamic and actionable insights for better decision-making and resource management. Despite these promising benefits, several challenges impede the widespread adoption of DT technology, such as technological integration, data consistency, organisational adaptation, and cybersecurity concerns. Addressing these challenges requires inter-disciplinary collaboration, standardization of data formats, and the development of universal design and development platforms for DTs. This paper provides a comprehensive review of DT definitions, applications, capabilities, and challenges within the Architecture, Engineering, and Construction (AEC) industries. This paper provides important insights for researchers and professionals, helping them gain a more comprehensive and detailed view of DT. The findings also demonstrate the significant impact that DTs can have on this sector, contributing to advancing DT implementations and promoting sustainable and efficient building management practices. Ultimately, DT technology is set to revolutionize the AEC industries by enabling autonomous, data-driven decision-making and optimizing building operations for enhanced productivity and performance.

DFT calculations on the photoisomerization reactions of pyridazine N-oxide derivatives are presented. The irradiation of 3,6-diphenylpyridazine N-oxide allowed to obtain the first excited singlet state that underwent to a ring opening reaction induced to the oxygen migration to the adjacent carbon atom, with the formation of a diazo derivative. This intermediate can give a ring closure reaction to give a pyrazole derivative, or, with a higher transition energy, it can lose nitrogen allowing the formation of 2,5-diphenylfuran. The irradiation of 3-phenylpyridazine N-oxide allowed the formation only of 2-phenylfuran. In this case, calculations allowed to explain this behavior. The first excited singlet state gave a photoisomerization reaction with the formation of the corresponding diazo intermediate. This intermediate could not be converted into the corresponding pyrazole derivative because it was converted into a N-formyl pyrazole never reported in literature. The only possible reaction is the loss of nitrogen and the formation of 2-phenylfuran.

The study of hydrothermal travertines contributes to the understanding of the interaction between physico-chemical processes and the role played by microbial mats and biofilms in influencing carbonate precipitation. Three active travertine sites were investigated in Central Italy to identify the types of carbonate precipitates and the associated microbial mats at varying physico-chemical parameters. Carbonate precipitated fabrics at the decimetre- to millimetre-scale and microbial mats vary with decreasing water temperature: a) at high temperature (55-44°C) calcite or aragonite crystals precipitate on microbial mats of sulphide oxidizing, sulphate reducing and anoxygenic phototrophic bacteria forming filamentous streamer fabrics, b) at intermediate temperature (44-40°C), rafts, coated gas bubbles and dendrites are associated with Spirulina cyanobacteria and other filamentous and rod-shaped cyanobacteria, c) low temperature (34-33°C) laminated crusts and oncoids in a terraced slope system are associated with diverse Oscillatoriales and Nostocales filamentous cyanobacteria, sparse Spirulina and diatoms. At the microscale, carbonate precipitates are similar in the three sites consisting of prismatic calcite (40-100 µm long, 20-40 µm wide) or acicular aragonite crystals organized in radial spherulites, overlying or embedded within biofilm EPS (Extracellular Polymeric Substances). Microsparite and sparite crystal size decreases with decreasing temperature and clotted peloidal micrite dominates at temperatures &lt; 40°C, also encrusting filamentous microbes. Carbonates are associated with gypsum and Ca-phosphate crystals; EPS elemental composition is enriched in Si, Al, Mg, Ca, P, S and authigenic aluminium-silicates form aggregates on EPS. This study confirms that microbial communities in hydrothermal travertine settings vary as a function of temperature. Carbonate precipitate types at the microscale do not vary considerably, despite different microbial communities suggesting that travertine precipitation, driven by CO2 degassing, is influenced by biofilm EPS acting as template for crystal nucleation (EPS-mediated mineralization) and affecting the fabric types, independently from specific microbial metabolism.

Fungi are rich sources of secondary metabolites of agrochemical, pharmaceutical and food importances, such as mycotoxins, antibiotics and antitumor agents. Secondary metabolites play vital roles in fungal pathogenesis, growth and development, oxidative status modulation, and adaptation/resistance to various environmental stresses. LaeA contains an S-adenosylmethionine binding site and displays methyltransferase activity. The members of velvet proteins include VeA, VelB, VelC, VelD and VosA, for each member with a velvet domain. LaeA and velvet proteins can form multimeric complexes such as VosA-VelB and VelB-VeA-LaeA. They belong to global regulators and are mainly impacted by light. One of their most important functions is to regulate gene expression that are responsible for secondary metabolite biosynthesis. The aim of this mini-review is to represent the newest cognition on the biosynthetic regulation of mycotoxins and other fungal secondary metabolites by LaeA and velvet proteins. In most cases, LaeA and velvet proteins positively regulated production of fungal secondary metabolites. The regulated fungal species mainly belong to the toxigenic fungi from the genera of Alternaria, Aspergillus, Botrytis, Fusarium, Magnaporthe, Monascus, and Penicillium for the production of mycotoxins. We can control secondary metabolite production to inhibit the production of harmful mycotoxins while promoting the production of useful metabolites by global regulation of LaeA and velvet proteins in fungi. Furthermore, the regulation by LaeA and velvet proteins should be a practical strategy in activating silent biosynthetic gene clusters (BGCs) in fungi to obtain previously undiscovered metabolites.

Background/Objectives: The latest WHO classification underscores the importance of the complete blood count (CBC) and cell morphology assessment in diagnosing lymphoid neoplasms. This study evaluated the diagnostic role of Research Use Only (RUO) parameters from the BC-6800 Plus Mindray analyzer in differentiating cell chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), and other lymphoproliferative disorders. Methods: CBCs were performed on 90 patients (66% male, median age 67 years) with pathological blood counts (ALL, n=14; CLL, n=47; other lymphoproliferative disorders, n=29) at Novara’s University Hospital. Univariable and multivariable logistic regression assessed the association of basic (WBC, Hb, RDW, NE#, LY#, MO#, PLT) and research cell parameters (NLR, NMR, LMR, NeuX, NeuY, NeuZ, LymX, LymY, LymZ, MonX, MonY, MonZ). Results: In multivariable analysis, Hb (p=0.02), NeuY (p=0.04), and MonY (p=0.01) independently predicted CLL versus ALL, correctly classifying 93.4% of cases (AUC 0.91, 95% CI 0.81-1.0). MO# (p=0.003), LymY (p&lt;0.0001), and MonY (p=0.004) were independent predictors of CLL versus other lymphoproliferative disorders, classifying 77.6% of cases (AUC 0.86, 95% CI 0.78-0.95). NeuZ (p=0.01) and NeuY (p=0.04) independently predicted ALL versus other lymphoproliferative disorders, classifying 93% of cases (AUC 0.98, 95% CI 0.95-1.0). Conclusions: The use of RUO parameters offers valuable, cost-effective support in the early diagnosis of ALL, CLL, and other lymphoproliferative disorders.

Relationships between geoheritage and cultural heritage are increasingly becoming a topic of study, especially in urban contexts. Their integrated reading adds value for educational and urban geotourism purpose, being the latter an emerging sector of sustainable tourism. The case study of the monumental complex of San Francesco le Moniche, built in the ancient Norman county Aversa, in the northern Campania (Italy), is analyzed here. The cultural heritage of the monumental complex and the additional value associated with the natural heritage (geological and geomorphological context, building stones) have been linked. The building stratification of the complex has been read not only from documentary sources, but also from the distribution and architecture of the existing underground cavities, the building stones, from ancient images and even postcards, integrating disciplines such as geosciences, architecture, archaeology, speleology, engineering. The results provide a clear example of a geoheritage-cultural heritage interface and the importance of an integrated approach in the valorization of the cultural and natural heritage of urban areas. The results allowed us to improve the knowledge of the study site and provide useful tools for the planning of future targeted investigations.

Infrared thermography is a contactless imaging technique, useful to measure surface temperature at distance which has been widely applied in animal production. The possible applications within the pig husbandry include sow heat detection, reduction of the incidence of neonatal mortality, recognition of febrile state caused by pathogens, study of metabolic efficiency, evaluation of stress caused by heat, by constraints, or by aggressive interaction and meat quality prediction. Even if this technique could be easily influenced by environmental factors, the continuous improvement in the procedures and the decrease in the cost of the equipment will allow in the next future new and more applications in swine farming.

Ferritin is an indirect marker for total body iron stores. Comparison of the ferritin concentrations in the meconium with the concentrations of proteins regulating iron metabolism could aid better understanding of principles behind the adjustment between the fetal iron pool and newborn body size. Ferritin, transferrin, haptoglobin, ceruloplasmin, lactoferrin, myeloperoxidase, neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin concentrations were measured by ELISA in meconium samples from 122 neonates. The neonates were classified according to the meconium ferritin tertiles and the values were collated with the meconium concentrations of other proteins and newborn body weight and length measurements. Increasing ferritin concentrations in meconium in consecutive tertiles (p < 0.05) were parallel to increased NGAL concentrations (p < 0.05). The interrelationships between the meconium concentrations of transferrin, haptoglobin and NGAL as well as between myeloperoxidase, calprotectin and lactoferrin are maintained in all subsequent tertiles of ferritin concentrations, (p < 0.05). In contrast to ferritin, increasing meconium NGAL concentrations in consecutive tertiles were linked to increased concentrations of transferrin, haptoglobin, lactoferrin and myeloperoxidase (p < 0.05) and of calprotectin, ferritin and ceruloplasmin (p < 0.1). Meconium ceruloplasmin concentrations correlate exclusively with neutrophil granule proteins, i.e. myeloperoxidase, NGAL, lactoferrin and calprotectin (p < 0.05). Meconium ferritin concentrations negatively correlates with birth weight (r= -0.20) and length (r= -0.31) of neonates, whereas NGAL concentrations just with birth length (r= -0.26). The remaining proteins did not show such relationships with the size of the newborn. High meconium concentrations of both ferritin and NGAL may specifically characterize neonates of smaller size. High meconium concentrations of both ferritin and NGAL may specifically characterize neonates with lower body measurements. Correlations between meconium transferrin, haptoglobin and NGAL may confirm the interrelationships of these proteins for proper iron control and transport in the intrauterine environment. Meconium ceruloplasmin concentrations may reflect the control of neutrophil activity in utero.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Despite new methods of diagnostics and treatment as well as extensive biological and immunosuppressive treatment, the etiology of RA is not fully understood. Moreover, the problem of diagnosis and treatment of RA patients is still current and affects a large group of patients. It is suggested that these ER-related features may impair adaptation to chronic stress, inferring the risk of rheumatoid arthritis. The main goal in this study was evaluation of changes in mRNA translation to determine chronic ER stress conditions in rheumatoid arthritis patients. The study group consist of 86 individuals including total 56 rheumatoid arthritis patients and 30 healthy controls. The expression level of mRNA form blood samples of RA patients as well as controls of the PERK-UPR associated genes: p-eIF2, BCL-2, PERK, ATF4, BAX were investigated by Real-Time qPCR. GAPDH expression was used as a standard control. Considering the median, the expression of PERK, BCL-2, p-eIF2, ATF4, BAX was found to be significantly increased in the blood of RA patients compared with the control group. The p-value for the PERK gene was 0.0000000036, the p-value for the BCL-2 gene was 0.000000014, the p-value for the p-eIF2 gene was 0.006948, the p-value for the ATF4 gene was 0.0000056 and the p-value for the BAX gene was 0.00019, respectively. Thus, it can be concluded that targeting of the components of the PERK-dependent UPR signaling pathway via small-molecule PERK inhibitors, may contribute to the development of novel, innovative treatment strategies against rheumatoid arthritis.

This research presents the creation of a Virtual Reality experience for the Balzi Rossi museum, commemorating the centenary of Prince Albert I Grimaldi's archaeological work at the site. The project, a collaboration between the University of Genoa's 3D Lab Factory, Eurodrone, and the Balzi Rossi archaeological museum, aims to preserve and convey the site's heritage through advanced VR technology. Initially employing Unreal Engine 4, the team used photogrammetry for 3D reconstruction of the "Caviglione" and "Florestano" caves, notable for their ancient rock engravings. This first VR model, despite hardware limitations, provided an interactive exploration of the site. The subsequent development phase utilized Unreal Engine 5, incorporating Nanite technology for enhanced visual fidelity. This advancement resulted in a more detailed and immersive VR experience, presenting the Balzi Rossi cliff across different historical periods, including the Würm glaciation. Key to this phase was optimizing the VR experience for performance, focusing on stable frame rates and minimizing motion sickness, and integrating a multi-lingual interface for broader accessibility. Since November 2023, the VR setup at the Balzi Rossi Museum has been an educational and interactive feature, enabling visitors to explore the site's history virtually. This research demonstrates the potential of VR in cultural heritage preservation and education, providing a foundation for future technological improvements in the field.

Osteosarcoma (OS) are the most prevalent malignant bone tumors in adolescents and young adults.. OS cells grow in a permissive local microenvironment which modulates their behavior and facilitates all steps in tumor development (e.g., proliferation/quiescence, invasion/migration, drug resistance) and contributes to their intrinsic heterogeneity. The lung parenchyma is the most common metastatic site in OS, and metastatic foci are frequently associated with a poor clinical outcome. Although multiple factors may be responsible for the disease, including genetic mutations (e.g., Rb, p53), the molecular mechanism of development of OS remains unclear and the conventional treatment for OS is still based on a sequential approach that combines chemotherapy and surgery. Also, despite the increase in clinical trials, the survival rates for OS have not improved. Non-specific targeting therapies thus show poor therapeutic effects with side effects at high doses. For these reasons, many efforts have been done to characterize the complex genome of osteosarcoma thanks to the whole exome analysis with the aim to identify predictive biomarkers to give to these patients a better therapeutic option. This review aims to summarize and discuss the main recent advances in OS molecular research for precision medicine.

Proteins possess complex three-dimensional structures, and these structures are stable only within specific ranges of temperature which mostly correspond to the temperature ranges of the host organisms. However, few exceptional proteins, called heat-stable proteins, are stable at temperatures that are substantially higher than those tolerated by the host organisms themselves. Most of the heat-stable proteins possess heat stability to perform their functions at high temperatures, but some of them are intrinsically heat-stable due to their structure. Heat-stable proteins are usually divided into three or four groups depending upon the intricacies of their structures and thermal behaviors. Their peculiar property, i.e. heat-stability, makes them very valuable in applications such as polymerase chain reaction, industrial processes requiring high temperature, and protein engineering. Heat-stability also makes it feasible to purify such proteins, from the rest of the heat-labile proteins, using a simple heat-treatment method. Moreover, heat treatment can be used as a combined cell-lysis and protein purification step which, as compared to conventional methods, can result in a higher yield of heat-stable proteins. Furthermore, some special heat-stable proteins, i.e. intrinsically disordered proteins (which include the proteins involved in important neurodegenerative diseases), need heat-treatment step, in some cases, as the only way for their successful purification and study. Hence, this paper provides a first-ever comprehensive review of all major aspects of heat-stable proteins, i.e., their structure, evolution, classification, significance, and heat-treatment mediated purification.

The Zika virus (ZIKV) is a mosquito-borne Flavivirus and can be transmitted through an infected mosquito bite or through human-to-human interaction by sexual activity, blood transfusion, breastfeeding or perinatal exposure. After the 2015-2016 outbreak in Brazil, a strong link between ZIKV infection and microcephaly emerged. ZIKV specifically targets human neural progenitor cells, suggesting that proteins encoded by ZIKV bind and inactivate host cell proteins leading to microcephaly. Here, we present a systematic annotation of interactions between human proteins and the seven non-structural ZIKV proteins corresponding to a Brazilian isolate. The interaction network was generated by combining tandem-affinity purification followed by mass spectrometry with yeast two-hybrid screens. We identified 150 human proteins, involved in distinct biological processes, as interactors to ZIKV non-structural proteins. Our interacting network is composed of proteins that have been previously associated with microcephaly in human genetic disorders and/or animal models. This study builds on previously published interacting networks of ZIKV and genes related to autosomal recessive primary microcephaly to generate a catalog of human cellular targets of ZIKV proteins implicated in processes related to microcephaly in humans. Collectively, this data can be used as a resource for future characterization of ZIKV infection biology and help create a basis for the discovery of drugs which may disrupt the interaction and reduce the health damage to the fetus.

Rett syndrome (RTT) is an X-linked neurodevelopment disorder associated with the single monogenic mutation in methyl-CpG binding protein 2 (MeCP2) in up to 95% of cases. The growing number of genome-wide association studies and incomplete concordance for autoimmune diseases in monozygotic twins concur to support the involvement of environmental factors, like infectious agents or chemicals, in the breakdown of tolerance leading to autoimmunity. In fact, the coexistence of a perturbation of the immune system in RTT patients has been previously hypothesized. We herein explored the hypothesis that an autoimmune component derived from environmental bacterial infection of non typeable Haemophilus influenzae may coexist in RTT. At this purpose we screened sera from RTT syndrome patients, non-RTT pervasive developmental disorders patients and healthy controls with the hyperglucosylated adhesin protein HMW1ct(Glc) used as a precise antigen in ELISA in order to identify specific antibodies to N-glucosylation sites. Results showed that HMW1ct(Glc) is able to significantly discriminate antibodies among RTT sera and controls. Competitive ELISA confirmed the specific interaction between antibodies characteristic of RTT syndrome and the N-glucosylation motifs of the bacterial adhesin protein HMW1ct(Glc).

The maintenance of traditional agricultural practices in protected small islands is closely linked to the preservation of the land, the protection of natural resources, and the conservation of local traditions. For this purpose, the Tuscan Archipelago National Park promoted the census of ancient horticultural varieties preserved by some farmers on the island of Elba. The survey revealed a deep-rooted historical, cultural, social, and economic link between this germplasm and the island’s territory. A scientific characterization of the landrace under ethnobotanical, morphological, and genetic aspects was carried out. Among these local varieties, two landraces of the Brassica species and three landraces of the Phaseolus species were identified and analyzed in this study. To ascertain their distinguishability and uniqueness, similar varieties were also identified based on morpho-physiological characteristics or territorial proximity and compared with the Elban landraces. Morpho-phenological data were collected, and molecular analyses were carried out using Simple Sequence Repeats (SSR) markers. Ten different SSR loci were considered for the Phaseolus species and nine for the Brassica species. The Tuscan Archipelago landraces showed a high level of internal variability but were clearly distinct from each other and from the analyzed varieties, as shown by AMOVA (Analysis of Molecular Variance). Their distinctness was further highlighted by the UPGMA dendrogram obtained from the genetic distance matrix. The same results were confirmed by Principal Coordinate Analysis (PCoA). This study confirms the peculiarity of the Elban landraces, their biodiversity is a heritage to be safeguarded, which can also be used in future breeding programs. These ancient Elban landraces were allocated to local farmers (most were young farmers) to protect them from extinction and to promote more resilient varieties cultivation compared to commercial hybrids widely spread in the area. Local farmhouses also play a strategic role in safeguarding the germplasm and dissemination of sustainable agricultural practices. There is high demand for ancient Elban landraces, this has led to the development of a new local economy balanced between agricultural tradition and innovation.

Darier disease (DD) is an autosomal dominant disorder due to mutation of ATP2A2 gene causing an isolated skin manifestation based on keratinocyte disconnection and apoptosis. Systemic manifestations of DD have not been demonstrated so far although a high incidence of neuropsychiatric syndromes suggest an involvement of central nervous system. A Novel ATP2A2 Gene Mutation c.118G>A, causing keratinocyte and cardiomyocyte disconnection in Darier disease, is reported. Their common pathologic pathway, still unreported, was documented by both skin and left ventricular endomyocardial biopsy because of cardiac dilatation and dysfunction appeared several decades after skin manifestations.Keratinocyte disconnection was paralleled by cardiomyocyte separation at lateral junction. Cardiomyocyte separation was associated to cell disarray, sarcoplasmic reticulum dilatation and increased myocyte apoptosis. Clinically, hyperkeratotic skin papules were associated to chest pain, severe muscle exhaustion and ventricular arrhythmias that improved following administration of aminophylline, a phosphodiesterase inhibitor enhancing SERCA2 protein phosphorylation.Specific mutations of ATP2A2 gene may cause cardiac involvement in patients with DD. Cardiac pathologic changes are similar to those documented in the skin including cardiomyocyte disconnection that promotes precordial pain and cardiac arrhythmias. Phosphodiesterase inhibitors, enhancing SERCA2 protein phosphorylation may substantially attenuate the symptoms.

This study presents the interaction with human host metabolism of SARS-CoV-2 ORF7b protein (43 aa), using a Protein-Protein-Interaction Networks analysis. After pruning, we selected from BioGRID the 51 most significant proteins among 2,753 proven interactions and 1,708 interactors, specific to ORF7b. We used these proteins as functional seeds and we got a significant network of 551 nodes via STRING. We performed topological analysis and calculated topological distributions by Cytoscape. Seven high ranked proteins as hub and seven as bottleneck following a hub-and-spoke network-architectural-model were found. Through this interaction model, we identified significant GO-processes (5,057 terms in 15 categories) induced in human metabolism by ORF7b. High statistical significance processes of dysregulated molecular cell mechanisms by the action of ORF7b were discovered. We detected disease-related human proteins and their involvement in metabolic roles, how they relate in a distorted way to signaling and/or functional systems, in particular intra- and inter-cellular signaling systems and the molecular mechanisms that supervise to programmed cell death, with mechanisms similar to that of cancer metastasis diffusion. A cluster analysis showed 10 compact and significant functional clusters, where two of them overlap in a Giant-Connected-Components core of 206 total nodes. These two clusters contain most of the high-rank nodes. ORF7b mainly acts through these two clusters, inducing most of the metabolic dysregulation. We conducted a co-regulation, transcriptional analysis by hub and bottleneck proteins. This analysis allowed us to define the transcription factors and miRNAs that control the high-ranking proteins and the dysregulated processes, within the limits of the poor knowledge that these sectors still impose.

Cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) are two of the four major chronic non-communicable diseases (NCDs), representing the leading cause of death worldwide. Several studies demonstrate that endothelial dysfunction (ED) plays a central role in the pathogenesis of these chronic diseases. Although it is well known that systemic chronic inflammation and oxidative stress are primarily involved in the development of ED, recent studies have shown that perivascular adipose tissue (PVAT) is implicated in its pathogenesis, also contributing to the progression of atherosclerosis and to insulin resistance (IR). In this review we describe the relationship between PVAT and ED, and we also analyse the role of PVAT in the pathogenesis of CVDs and T2DM, further assessing its potential therapeutic target with the aim of restoring normal ED and reducing global cardiovascular risk.

Childhood emotional abuse (CEA) has been linked to a range of unfavorable outcomes, including the development of unhealthy personality traits and maladaptive coping mechanisms and behaviors. In this study, our objective was to investigate whether neuroticism and perfectionism act as mediators in the relationship between CEA and workaholism, while also evaluating the gender invariance of the hypothesized model. A cohort of 1176 young workers, with a balanced gender representation (50% female), aged 18-25, participated in the study by completing self-report questionnaires. The results revealed significant connections between all direct and indirect links, indicating a complex interplay between childhood emotional abuse, neuroticism, perfectionism, and workaholism. Importantly, the mediation model exhibited no significant differences between genders, suggesting that the identified relationships are consistent across both male and female participants. This research underscores the critical importance of early identification of childhood emotional abuse and advocates for the implementation of trauma-informed care to address the negative consequences of emotional abuse, ultimately aiming to prevent the development of workaholism. Furthermore, the findings emphasize the necessity for tailored prevention strategies, focusing on mitigating neuroticism and perfectionism as potential pathways for effective therapeutic interventions.

The BET family of proteins is characterized by the presence of two tandem bromodomains and an extra-terminal domain. The mammalian BET family of proteins comprises Brd2, Brd3, Brd4, and Brdt, which are encoded by paralogous genes that may have been generated by repeated duplication of an ancestral gene during evolution. Bromodomains that can specifically bind acetylated lysine residues in histones serve as chromatin-targeting modules that decipher the histone acetylation code. BET proteins play a crucial role in regulating gene transcription through epigenetic interactions between bromodomains and acetylated histones during cellular proliferation and differentiation processes. On the other hand, BET proteins have been reported to mediate latent viral infection in host cells and be involved in oncogenesis. Human BRD4 is involved in multiple processes of the DNA virus life cycle, including viral replication, genome maintenance, and gene transcription through interaction with viral proteins. Aberrant BRD4 expression contributes to carcinogenesis by mediating hyperacetylation of the chromatin containing the cell proliferation-promoting genes. BET bromodomain blockade using small-molecule inhibitors gives rise to selective repression of the transcriptional network driven by c-Myc. These inhibitors are expected to be potential therapeutic drugs for a wide range of cancers. This review presents an overview of the basic roles of BET proteins and highlights the pathological functions of BET and the recent developments in cancer therapy targeting BET proteins in animal models.

Stroke represents one of the neurological diseases most responsible for death and permanent disability in the world. Different factors, such as thrombus, emboli and atherosclerosis, take part in the intricate pathophysiology of stroke. Comprehending the molecular processes involved in this mechanism is crucial to developing new, specific and efficient treatments. Some common mechanisms are excitotoxicity and calcium overload, oxidative stress, and neuroinflammation. Furthermore, non-coding RNAs (ncRNAs) are critical in pathophysiology and recovery after cerebral ischaemia. ncRNAs, particularly microRNAs, and the long non-coding RNAs (lncRNAs) are essential for angiogenesis and neuroprotection, and they have been suggested to be therapeutic, diagnostic and prognostic tools in cerebrovascular diseases, including stroke. This review summarizes the intricate molecular mechanisms underlying ischemic and hemorrhagic stroke and delves into the function of miRNAs in the development of brain damage. Furthermore, we will analyze new perspectives on treatment based on molecular mechanisms in addition to traditional stroke therapies.

Background: Blood pressure (BP) is characterized by a circadian rhythm (Circr), with lower nighttime values, called dipping. Non-dipping is associated with higher CVD risk. The Circr of urinary sodium excretion (NaCle), peaking during the day, is linked to BP patterns. Physical ac-tivity (PA) is known to improve BP control and enhance the dipping phenomenon, but its possi-ble effect on NaCle remains unclarified. Objectives: This study aimed to investigate the correla-tion between PA and the Circr of NaCle and to determine if the relationship is independent of age, sex, BP values, dipping pattern, and salt intake. Methods: A cross-sectional analysis was conducted using data from the Ticino Epidemiological Stiffness Study, involving 953 participants in Switzerland. Data collection included standardized questionnaires, blood samples, 24-hour urine collections, and ambulatory BP monitoring. Participants were categorized into sedentary, partially active, and active. The effect of PA, NaCl intake, and dipping on the day/night NaCle ratio, was assessed with multivariable linear regressions. Results: Participants median age 49 years, with 78% having normal BP values and 47% exhibiting a dipping pattern. 51% were classi-fied as sedentary and 22% as partially active. The median NaCl intake was 7.9 g/day. The youngest subjects had a higher hourly NaCle ratio compared to older subjects. Higher NaCl in-take correlated with increased BP, phenomenon more pronounced in men and younger subjects. The hourly day/night NaCle ratio positively correlates with dipping; however, PA did not show a significant correlation with the NaCle ratio. Conclusion: This study indicates that while the day/night NaCle ratio correlates with the dipping pattern, PA is unrelated to the circadian rhythm of renal sodium handling. The beneficial effects of PA on BP and cardiovascular health thus appear to be mediated through mechanisms other than NaCle. These are explorative find-ings only, but relativize the need for further investigations on the topic.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, wings, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects and all other arthropods. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. As a means of renaming this protein family, this review article discusses the latest findings (“CSP” is attached to the tail of bigger intracellular proteins) and attempts to compel all the data. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins) and use at least for abbreviations for distinctive animal proteins the common peptide 5-letter code, such as “Bommo-4CSPs”.

Intrinsically Disordered Proteins (IDPs) play crucial roles in signal transduction, cell differentiation, and transcriptional regulation. Many disrupted genes associated with mental disorders are identified as IDPs, and emerging evidence suggests the functional role of IDPs in neuropsychiatric disorders. However, few studies comprehensively explore the functional association between protein disorder properties and different mental diseases. To address this gap, we collected disrupted gene sets for seven mental diseases (MDD, SCZ, BP, ID, AD, ADHD, ASD) and a control gene set from normal brains using DisGeNET and GeneCards databases. The state-of-the-art predictor IUPred2A was then utilized to calculate the disorder properties , followed by a thorough comparison between the disordered proteins in mental diseases and healthy controls. Functional enrichment analysis and protein-protein interaction networks were conducted to investigate the IDPs’ functional roles in psychiatric diseases. Additionally, we demonstrated the role of IDPs in protein binding formations through a case study of alpha-synuclein using protein docking. Our findings reveal that differentially expressed proteins in mental disorders, especially in ASD and ADHD, exhibit more IDPs than those in healthy controls. IDPs in psychiatric disorders are significantly enriched in neurodevelopmental pathways and play an important role in in gene expression regulation. Our results indicate distinct functional patterns of disorder proteins among mental diseases and healthy controls. When comparing the IDPs between ASD and ADHD, we observed that IDPs in ADHD are more likely linked to the synaptic signaling and regulation, while IDPs in ASD are more tendentiously related to diverse and complex biological processes. Our work offers valuable insights into the important functions of IDPs in psychiatric disorders, enhancing our understanding of the molecular mechanisms involved in psychiatric disorders.

The Rose grain aphid, a notable agricultural pest, releases saliva while feeding. Yet, there is a need for a comprehensive understanding of the specific identity and role of secretory proteins released during probing and feeding. Therefore, a combined transcriptomic and proteomic approach was employed to identify putative secretory proteins. The transcriptomic sequencing result led to the assembly of 18030 unigenes out of 31344 transcripts. Among these, 705 potential secretory proteins were predicted and functionally annotated against publicly accessible protein databases. Notably, a substantial proportion of secretory genes (71.5%, 69.08%, and 60.85%) were predicted to encode known proteins in Nr, Pfam, and Swiss-Prot databases, respectively. Conversely, 27.37% and 0.99% of gene transcripts were predicted to encode known proteins with unspecified functions in the Nr and Swiss-Prot databases, respectively. Meanwhile, the proteomic analysis result discovered, 30 salivary proteins. Interestingly, most salivary proteins (53.3% proteins) showed close similarity to A. craccivora, while 36.67% to A. pisum and A. glycines. However, to verify the expression of these secretory genes and characterize the biological function of salivary proteins further intervention should be geared towards gene expression and functional analysis.

Abstract: A. baumannii exhibits resilience in harsh environments and progressively develops resistance to diverse antibacterial agents over time. This adaptability poses a significant challenge in treating an infection caused by this bacterium within healthcare settings. The presence of peptidoglycan, a crucial precursor for cell wall synthesis, contributes to this challenge. Peptidoglycan serves not only as a structural support in bacterial cells but also provides protection against adverse environmental conditions. The synthesis of the peptidoglycan layer involves a group of substrates such as N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), within a three-partitioned process occurring in the membrane, periplasmic space, and cytoplasm of each bacterium. Initiated in the cytoplasm and extending to the inner cell membrane, this synthesis starts with the production of nucleotide precursors. The first step involves the synthesis of UDP-GlcNAc, orchestrated by Glm (GlmS, GlmM, and GlmU) enzymes using fructose-6-phosphate. Subsequently, enzymes from the Mur family, namely MurB, MurA, MurD, MurC, MurI, MurF, and MurE, synthesize UDP-N-acetylmuramyl-pentapeptide (UDP-Mpp) from UDP-GlcNAc. Concurrently, on the cytosolic side, the production of membrane-surrounded undecaprenyl phosphate occurs, involving membrane-side proteins MraY and MurG in the biosynthesis of peptidoglycan. This review emphasizes updated information on Mur family proteins, encompassing physicochemical properties, nature of binding site, number and type of binding site residues, functional domain details, three-dimensional structural aspects, and their functions within bacterial cells. Special attention is directed towards their enzymatic role in peptidoglycan biosynthesis due to the limited availability of precursors in the market. Additionally, the review provides a comprehensive summary of existing inhibitors and ongoing efforts in identifying new targeted inhibitors, recognizing these enzymes as potential candidates for antibacterial drug design and discovery.

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal-fetal complications with possible repercussions even in the long-term. Here, we analyzed the changes of plasma redox balance and the effects of plasma on human umbilical cord mesenchymal cells (hUMSCs) in AMA pregnant women (patients) at various timing of pregnancy. One hundred patients and twenty pregnant women younger than 40 years (controls) were recruited, and evaluated at various timings during pregnancy until after delivery. Plasma samples were used to measure the thiobarbituric acid reactive substances (TBARS), glutathione and nitric oxide (NO). In addition, plasma was used to stimulate the hUMSCs, which were tested for cell viability, reactive oxygen species (ROS) and NO release. The obtained results showed that throughout pregnancy until after delivery in patients the levels of plasma glutathione and NO were lower than those of controls, while those of TBARS were higher. Moreover, plasma of patients reduced cell viability and NO release, and increased ROS release in hUMSCs. Our results highlighted alterations in the redox balance and the presence of potentially harmful circulating factors in plasma of patients They could have clinical relevance for the prevention of complications related to AMA pregnancy.

Synucleins are a family of small, soluble proteins mainly expressed in neural tissue and in certain tumors. Since their discovery, tens of thousands of scientific reports have been published about this family of proteins as they are associated to severe human diseases. Although the physiological function of these proteins still elusive, their relation with neurodegeneration and cancer was clearly described over the years. In this review, we summarize data connecting synucleins and cancer, going from the structural description of these molecules, to their involvement in tumor-related processes, and discuss the putative use of this proteins as cancer molecular biomarkers.

The Coronavirus Disease 2019 (COVID-19) is a new viral infection caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2). Genomic analyses have revealed that SARS-CoV-2 is related to Pangolin and Bat coronaviruses. In this report, a structural comparison between the Sars-CoV-2 Envelope and Membrane proteins from different human isolates with homologous proteins from closely related viruses is described. The analyses here reported show the high structural similarity of Envelope and Membrane proteins to the counterparts from Pangolin and Bat coronavirus isolates. However, the comparisons have also highlighted structural differences specific of Sars-CoV-2 proteins which may be correlated to the cross-species transmission and/or to the properties of the virus. Structural modelling has been applied to map the variant sites onto the predicted three-dimensional structure of the Envelope and Membrane proteins.

In mammals, Tripartite motif-containing (TRIM) proteins modulate the immune response by coordinating pro-inflammatory related processes such as antiviral restriction, cellular autophagy and inflammasome activation. In fish, TRIM proteins have been reported mainly in cyprinids (e.g., carp, zebrafish) and salmonids (rainbow trout). However, their molecular mechanisms and functions are still being described these animals. Our study focused on characterizing novel TRIM proteins involved in the innate immune response of gill cells from rainbow trout stimulated with LPS or poly(I:C). Also, a fish trial was performed to detect TRIM proteins of rainbow trout after a challenge with Flavobacterium psychrophilum, a salmonid bacterial pathogen. At in vitro level, the results showed that, among several TRIM proteins, OmTRIM25 triggered an LPS-induced expression of pro-inflammatory cytokines (TNF-α2 and IL-1β), suggesting a potential local modulatory function. Moreover, in the fish trial, while OmTRIM25 and finTRIM2 were up-regulated in the gills two days post infection (dpi), IL-1β and TNF-α2 reached their peaks of expression at four- and six-dpi. Finally, after delving into the function of OmTRIM25 by RNA interference (RNAi) gene-silencing, we propose that TRIM proteins such as OmTRIM25 are needed to induce the pro-inflammatory response in the gills of rainbow trout, which confirms their immunomodulatory function.

In the intricate dance between viruses and host cells, RNA-binding proteins (RBPs) serve as crucial orchestrators of gene expression and cellular processes. We will delve into the riveting realm of viral hijacking, where viruses deftly exploit host RBPs to manipulate cellular machinery for their replication and pathogenesis. Through a masterstroke of molecular subterfuge, viruses co-opt RBPs involved in various facets of RNA metabolism - from transcription to degradation - to promote viral gene expression and evade host immune defenses. This manipulation leads to global alterations in cellular RNA metabolism, impacting essential host genes vital for immune responses and homeostasis.Unveiling this clandestine alliance between viruses and RBPs is not just a scientific pursuit, but a critical imperative for devising innovative antiviral strategies to disrupt these interactions. By unraveling the intricate interplay between viral proteins and host RBPs throughout the viral life cycle - from entry to assembly - researchers aim to identify vulnerabilities that can be targeted for therapeutic intervention. Strategies such as disrupting viral protein-RBP interactions hold promise for inhibiting viral replication and curbing pathogenesis, offering a beacon of hope in the battle against viral infections.Our manuscript elucidates the indispensable roles played by RBPs in viral replication, translation, and pathogenesis, shedding light on the molecular mechanisms driving viral success. Delving deeper, it explores how viruses intricately entwine with host RBPs, manipulating cellular signaling pathways to create a hospitable environment for viral spread. By dissecting these manipulative tactics, researchers uncover new targets for antiviral therapy, envisioning a future where tailored interventions disrupt viral-host RBP interactions with precision and efficacy.As the narrative unfolds, the therapeutic implications of targeting RBPs or their interactions with viral proteins emerge as a promising frontier in the fight against viral infections. From small molecule inhibitors to RNA-based therapeutics, innovative approaches are on the horizon, offering new avenues for combatting viral diseases. We set the stage for future research, beckoning researchers to delve deeper into the molecular intricacies of viral hijacking of RBPs and charting a course towards novel therapeutic interventions that promise to reshape the landscape of antiviral therapy.\Ultimately, it beckons the scientific community to embark on a voyage of discovery, unraveling the secrets of viral hijacking of RBPs and paving the way for transformative advances in antiviral therapeutics. The stage is set for a new chapter in the battle against viral infections, where knowledge becomes the sword and innovation the shield against the pernicious machinations of viral pathogens.

The intricate functionality of the vertebrate retina relies on the interplay between neurotransmitter activity and calcium dynamics, offering important insights into de-velopmental processes, physiological functioning, and disease progression. Neuro-transmitters orchestrate cellular processes to shape the behavior of the retina under diverse circumstances. Despite research to elucidate the roles of individual neuro-transmitters in the visual system, there remains a gap in our understanding of the holistic integration of their interplay with calcium dynamics in the broader context of neuronal development, health, and disease. To address this gap, the present review explores the mechanisms used by the neurotransmitters glutamate, GABA, glycine, dopamine, and acetylcholine and their interplay with calcium dynamics. This con-ceptual outline is intended to inform and guide future research, underpinning novel therapeutic avenues for retinal-associated disorders.

Micro-Raman spectroscopy was carried out to evaluate the localized residual stresses in commercial Gallium Nitride-based devices, specifically AlGaN/GaN High Electron Mobility Transistors (HEMTs) in a novel packaging design provided by STMicroelectronics S.r.l. The packaging plays a key role in protecting the device core against the external environment, thus minimizing damages caused by mechanical shocks, exposure to light, and contact with chemicals, conjointly achieving an efficient heat dissipation rate. Even though the packaging is a required step for the proper functioning of ready-to-use electronic devices, its application typically may introduce mechanical stress to AlGaN/GaN HEMTs, which can result in various reliability issues. In this paper, we investigate the impact of packaging on residual stress by analyzing the frequency shift of the E2 Raman peak along GaN layers and at the GaN/Si interface. An extensive evaluation was conducted using both a packaged device and a wafer-level device. The correlation between Raman frequency shifts of the E2 mode was accurately quantified, revealing a stress mitigation of approximately 0.1 GPa. This reduction is ascribed to the compressive stress introduced by the packaging, which partially offsets the intrinsic tensile stress of the wafer-level device. The proposed methodology could, in principle, be implemented to improve the development of a packaging.

The role of astro- and microglial cells in the pathogenesis of epilepsy is currently under active in-vestigation. It is proposed that the activity of these cells may be regulated by agonists of peroxi-some proliferator-activated nuclear receptors (PPARs). The objective of this study was to investi-gate the effects of the PPAR β/δ agonist GW0742 (Fitorine) on the behavior and gene expression of astro- and microglial proteins involved in the regulation of epileptogenesis in rat brain in a lithi-um-pilocarpine model of temporal lobe epilepsy (TLE). A seven-day administration of GW0742 at a dose of 5 mg/kg/day has been shown to suppress TLE-related behavioral hyperactivity in the Open Field test and to attenuate the TLE-induced increase in gene expression and protein levels of astro- and microglial activation markers Gfap and Aif1 in the dorsal hippocampus and temporal cortex. Furthermore, GW0742 reversed the TLE-related increase in Lcn2 gene expression (a marker of the A1 phenotype of astrocytes) in the temporal cortex, the increase in the ratio of Nos2/Arg1 gene expression (markers of the M1/M2 phenotypes of microglia), and the decrease in Arg1 gene ex-pression in the dorsal hippocampus. The results suggest that GW0742 may mitigate behavioral and biochemical abnormalities in a lithium-pilocarpine model of TLE.

Meteorological observations over the last four decades are of paramount importance to investigate the ongoing climate change. The assessment of the reliability of any climatic time series is thus mandatory to draw correct conclusions. This evaluation involves homogeneity tests to detect artificial discontinuities whose identification is facilitated by metadata availability. In this work, daily minimum and maximum temperature measurements collected in Padua, Italy, between 1980 and 2022, are examined. Hourly observations began in 1993 and since the aim is to study long term behavior of the temperature, the focus is on daily averages and extremes. Over this period, the weather station of Padua center underwent many changes, in location or instrument; therefore, some tests have been used to identify and remove the effects of these variations and obtain a homogeneous time series. The homogeneity tests applied must be able to identify change-points both in the middle and at the extremes of the series. Some well-known absolute tests have been applied to investigate shift in the mean value: Standard Normal Homogeneity test (SNH), Buishand U and range tests, Pettitt test, F-test, STARS. Some relative tests have been applied too, which are generally more reliable than absolute tests, because they consider the information from neighboring stations. As relative tests rely on the homogeneity and quality of the reference series, several nearby stations and two reanalysis datasets (ERA5 and MERIDA) have been considered, to enhance the picture of the local situation and provide more robust conclusions. The applied tests identify change-points in the years in which a change in instrument or location of the station have occurred, confirming that these changes have compromised the homogeneity of the series. The sub-series obtained splitting the observations in correspondence of these change-points have been homogenized with respect a selected period; corrections must be applied also to future measurements to extend the time series properly.

The temperature variations caused by the climate changes taking place in the Basilicata region, southern Italy - Ionian Seaside of the Gulf of Taranto - on the territory of the DOP Matera vineyard, were studied by means of an analysis of temperature trends considering both the period of the vegetative-productive season of the vineyards and the whole year. Two datasets were analyzed for this study: data from ERA5-Land of the C3S Climate Data Store -relative to the 1981-2022 window- and data from 5 weather stations belonging to the agrometeorological network of the Lucanian Agency for Development and Innovation in Agriculture (SAL-ALSIA), relative to the 2000-2023 window. From the results of this study, it can be deduced that, for the historical period analyzed, the Matera DOP area showed a clear and worrying trend of increasing temperatures and, in par-ticular, minimum temperatures. This increase, moreover, is more evident at higher elevations than at lower elevations close to the sea. At lower altitudes, in fact, temperatures are strongly “buffered” by the thermoregulatory activity of the bordering Ionian Sea. It follows that the DOP Matera viticultural areas, and in particular the areas furthest from the coastal strip, will already have to adapt to severe climatic conditions that will undoubtedly affect the quality and typicality of the wines.

Background: Current management of COPD is predominantly focused on respiratory aspects. A multidimensional assessment including nutritional assessment, quality of life and disability provides a more reliable perspective of the true complexity of COPD patients. Methods: Prospective observational study of 120 elderly COPD patients at high risk of acute exacerbations. The Mini-Nutritional Assessment (MNA) was administered in addition to the usual respiratory assessment. The primary outcome was a composite of moderate or severe acute exacerbations during 52 weeks of follow-up. Results: The median MNA Short Form (SF) score was 11 (8-12), 39 participants (32.50%) had normal nutritional status, 57 (47.5%) were at risk of malnutrition and 24 (20%) were malnourished. Our multivariate linear logistic models showed that the MNA score was associated with dyspnea and respiratory symptoms severity assessed by the Modified British Medical Research Council (mMRC) and the COPD Assessment Test (CAT) score, with spirometric variables, in particular with the severity of airflow limitation based on the value of FEV1 and with poorer QoL as assessed by the EQ-5D-3 questionnaire. Cox regression analysis according to nutritional status based on the MNA score showed that COPD participants "at risk of malnutrition" and "malnourished" had a higher risk of moderate to severe acute exacerbations with a hazard ratio (HR) of 3.54 (p=0.002) and 8.20 (p=0.0001), respectively. Conclusion: Our study confirms the importance of assessing nutritional status in elderly COPD patients and its prognostic value.

Adhesive-invasive E. coli have been suggested to be associated with the development of Crohn's disease (CD). It is assumed that they can provoke the onset of the inflammatory process as a result of the invasion of intestinal epithelial cells, and then, due to survival inside macrophages, stimulate chronic inflammation and the development of granuloma. In previous reports, we have shown that passage of the СD isolate ZvL2 on minimal medium M9 supplemented with sodium propionate (PA) as a carbon source stimulates, and with glucose - inhibits the adherent-invasive properties and the ability to survive in macrophages. This effect was reversible and not observed for the laboratory strain K12 MG1655. We were able to compare the isogenic strain AIEС in two phenotypes - virulent (ZvL2-PA) and non-virulent (ZvL2-GLU). We showed that, unlike ZvL2-GLU, the ZvL2-PA activates the production of ROS and cytokines when interacting with neutrophils. The laboratory strain does not cause a similar effect. Differences in neutrophil NADH-oxidase activation and ζ potential for ZvL2-GLU and ZvL2-PA are associated with changes in the abundance of membrane proteins. Using differential 2D electrophoresis and LC-MS, we identified membrane proteins that may be associated with the activation of the virulence properties of the СD isolate ZvL2.

Orthohepadnavirus causes chronic hepatitis in a broad range of mammals, including primates, cats, woodchucks, and bats. Hepatitis B virus (HBV) X protein inhibits type-I interferon (IFN) signaling, promoting HBV escape from the innate immune system to establish persistent infection. However, whether X proteins of Orthohepadnavirus viruses in the other species have similar inhibitory activity remains unknown. Here, we investigated the anti-IFN activity of 17 Orthohepadnavirus X proteins derived from various hosts. We observed conserved activity of Orthohepadnavirus X proteins in inhibiting TIR-domain-containing adaptor protein inducing IFN-β (TRIF)-mediated IFN-β signaling pathway through TRIF degradation. X proteins from domestic cat hepadnavirus (DCH), a novel member of Orthohepadnavirus, inhibited mitochondrial antiviral signaling protein (MAVS)-mediated IFNβ signaling pathway comparable with HBV X. These results indicate that inhibition of IFN signaling is conserved in Orthohepadnavirus X proteins.

Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, some are conjugated to CRM197, a modified diphtheria toxin, and all contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. All of these proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. CRM197 is also present in Hib and meningitis vaccines. Equivalent similarities were found at lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable.

Dual localization or dual targeting refers to the phenomenon by which identical, or almost identical, proteins are localized to two (or more) separate compartments of the cell. From previous work in the field, we had estimated that a third of the mitochondrial proteome is dual targeted to extra-mitochondrial locations and suggested that this abundant dual targeting presents an evolutionary advantage. Here we set out to study how many additional proteins whose main activity is outside mitochondria are also localized, albeit at low levels, to mitochondria (eclipsed). To do this we employed two complementary approaches utilizing the α-complementation assay in yeast to uncover the extent of such eclipsed distribution: one systematic and unbiased and the other based on Mitochondrial Targeting Signal (MTS) predictions. Using these approaches, we suggest 280 new eclipsed distributed protein candidates. Interestingly, these proteins are enriched for distinctive properties compared to their exclusively mitochondrial-targeted counterparts. We focus on one unexpected eclipsed protein-family of the Triose-phosphate DeHydrogenases (TDH), and prove that indeed their eclipsed distribution in mitochondria is important for mitochondrial activity. Our work provides a paradigm of deliberate eclipsed mitochondrial localization, targeting and function, and should expand our understanding of mitochondrial function in health and disease.

Angiogenesis is a critical process in various physiological and pathological conditions, and snake venom disintegrins (SVDs) have been shown to be important regulators of this process. In this review, we explore the dual roles of SVD in angiogenesis, both as antiangiogenic agents by inhibiting integrin binding and interfering with vascular endothelial growth factors and as proangiogenic agents by enhancing integrin binding, stimulating cell migration and proliferation, and inducing neoangiogenesis. Studies in vitro and in animal models have demonstrated these effects and offer significant therapeutic opportunities. The potential applications of SVD in diseases related to angiogenesis, such as cancer, ocular diseases, tissue regeneration, wound healing, and cardiovascular diseases, are also discussed. Overall, SVDs are promising potential therapeutics, and further advances in this field could lead to innovative treatments for diseases related to angiogenesis.

The early elongation events in transcription or translational control in the N-terminal of genes are assuming critical roles in their heterologous expression. The secretory expression of the alkaline pectin lyase APL in B. subtilis were studied to explore the effects of the N-terminal 5-7 amino acids sequences of different signal peptides on gene transcription and protein secretion in this study. The first 5 amino acid sequences of the N-terminal of the signal peptide LipA were identified to play an important role in promoting the expression of APL for the first time. Meanwhile, it also revealed that the signal peptide LipA could lead to higher secretory expression than other signal peptides not because of its sequence structure associated with secretion is stronger but because the N-terminal sequences showed greater advantages in gene transcription. At this basis, the recombinant strain structed in this work showed a new record for the highest extracellular yields (12 295 U/ml) of APL in B. subtilis which was 1.9 times higher than that expressed in the recombinant Escherichia coli strain we had reported before. The novel theories revealed in this study would assuming significance roles for improving expression of foreign proteins in or out of the cells.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. The rise in airways epithelial barrier permeability alters the tissue homeostasis and allows the allergen and other external agents penetration. Different factors contribute to barrier impairment, such as eosinophilic infiltrate and allergens proteases action: the eosinophilic cationic proteins and the allergens' proteolytic activity have a central role in contributing to epithelial damage. In the airways, the allergens proteases degrade the epithelial junctional proteins allowing the allergen penetration and the uptake by dendritic cells. The increase in allergen-immune system interactions induce the release of the alarmins and the activation of type 2 inflammatory pathways causing, or worsening, the main symptoms at skin, bowel and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic proteases-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance and progression. We further will explore clinical and radiological potential biomarkers of airways remodeling in allergic asthma patients.

In this work, we explore the intrinsic disorder status of the three members of the synuclein family of proteins - α-, β-, and γ-synucleins. We also analyzed the peculiarities of the amino acid sequences and modeled 3D structures of the human synuclein family members to find potential effects of pathological mutations. Furthermore, we conducted a comparative sequence-based analysis of the synuclein proteins from various evolutionary distant species and evaluated their levels of intrinsic disorder using a set of commonly used bioinformatics tools. Next, we conducted a detailed functional disorder analysis of the proteins in the interactomes of the human synuclein family members using various web-based disorder analysis and prediction tools, such as RIDAO, D2P2 and FuzDrop. We identify that the interactome of human α-synuclein has relatively higher levels of intrinsic disorder, as compared to the interactomes of human β- and γ- synucleins. These observations highlight the critical importance of intrinsic disorder of human α-synuclein and its interactors in neuronal processes as compared to other proteins of the synuclein family.

Reinventing approved therapeutic proteins for a new dose, a new formulation, a new route of administration, an improved safety profile, a new indication, or a new conjugate with a drug or a radioactive source is a creative approach to benefit from the billions spent on developing new therapeutic proteins. These new opportunities were created only recently with the arrival of AI/ML tools and high throughput screening technologies. Furthermore, the complex nature of proteins offers mining opportunities that are not possible with chemical drugs; bringing in newer therapies without spending billions makes this path highly lucrative financially while serving the dire needs of humanity. This paper analyses several practical reinventing approaches and suggests regulatory strategies to reduce development costs significantly. This should enable the entry of hundreds of new therapies at affordable costs.

A plenty of theories on the origin of genetic codes have been proposed so far, yet all ignored the energetic driving force, its relation to the biochemical system, and most importantly, the missing “matchmaker” between proteins and nucleic acids. Here, a new hypothesis is proposed, according to which ATP is at the origin of the primordial genetic code by driving the coevolution of the genetic code with the pristine biochemical system. This hypothesis aims to show how the genetic code was produced e.g. by photochemical reactions in a protocell that derived from a lipid vesicle enclosing various life’s building blocks (e.g. nucleotides and peptides). At extant cell, ATP is the only energetic product of photosynthesis, and is at the energetic heart of the biochemical systems. ATP could energetically form and elongate chains of both polynucleotides and polypeptides, thus acting a “matchmaker” between these two bio-polymers and eventually mediating precellular biochemical innovation from energy transformation to informatization. ATP was not the only one that could drive the formation of polynucleotides and polypeptides, but favored by precellular selection. The protocell innovated a photosynthesis system to produce ATP efficiently and regularly with the aids of proteins and RNA/DNA. The completion of permanently recording the genetic information by DNA marked the dawn of cellular life operated by Darwinian evolution. The ATP hypothesis assumes or supports the photochemical origin of life, shedding light on the origins of both photosynthetic and biochemical systems, which remains largely unknown thus far. Based on ATP hypothesis, virus (like the new coronavirus) could not be the earliest life on Earth, as it has neither biochemical systems nor lipid bilayer membrane that provided relatively isolated environment for the development of protobiochemical reactions, although it owns the genetic code of a cellular life. Virus could not be a bridge between life and non-life, but is an anti-life substance, as it depletes cellular material for its own replication, and then spreads by destroying the host cells. It can be imagined that if cellular life are completely wiped out by the virus, the complete destruction of life on Earth would be inevitable.

Dictyostelium discoideum is gaining increasing attention as a model organism for the study of calcium binding and calmodulin function in basic biological events as well as human diseases. After a short overview of calcium-binding proteins, the structure of Dictyostelium calmodulin and the conformational changes effected by calcium ion binding to its four EF hands is compared to its human counterpart, emphasizing the highly conserved nature of this central regulatory protein. The calcium-dependent and -independent motifs involved in calmodulin binding to target proteins are discussed with examples of the diversity of calmodulin binding proteins that have been studied in this amoebozoan. The methods used to identify and characterize calmodulin binding proteins is covered followed by the ways Dictyostelium is currently being used as a system to study several neurodegenerative diseases and how it could serve as a model for studying calmodulinopathies such as those associated with specific types of heart arrythmia. Because of its rapid developmental cycles, its genetic tractability, and a richly endowed stock center, Dictyostelium is in a position to become a leader in the field of calmodulin research.

HD-Zip proteins are unique to plants, and contain a homeodomain closely linked to a leucine zipper motif, which are involved in dimerization and DNA binding. Based on homology in the HD-Zip domain, gene structure and the presence of additional motifs, HD-Zips are divided into four families, HD-Zip I–IV. Phylogenetic and bioinformatics analysis of HD-Zip genes using transcriptomic and genomic datasets from a wide range of plant species indicate that the HD-Zip protein class was already present in green algae. Later, HD-Zips experienced multiple duplication events that promoted neo- and sub-functionalizations. HD-Zip proteins are known to control key developmental and environmental responses, and a growing body of evidence indicates a strict link between members of the HD-Zip II and III families and the auxin machineries. Interactions of HD-Zip proteins with other hormones such as brassinolide and cytokinin have also been described. However, it is striking that among the genes regulated by REV, a HD-Zip III protein playing a key role in apical development, are genes that mediate ABA signaling. Furthermore, HAT1 and HAT3, two HD-Zip II proteins involved in key developmental processes, repress ABA biosynthesis and signaling, indicating an essential role of these factors in adjusting development to changing environment.

Background: Stroke is one of the leading causes of death and disability worldwide. The diagnosis of stroke remains largely clinical, yet widely used stroke scoring systems and brain imaging do not satisfactorily allow distinction of ischaemic stroke (IS) patients from stroke mimics (SM). Blood biomarkers are promising tools that could facilitate clinical triage. Methods: This study recruited 66 patients with IS and 24 SM. The levels of Glial fibrillary acidic protein (GFAP), Neuron-specific enolase (NSE), Neurofilament light chain (NfL) and blood-brain barrier (BBB) proteins [Occludin (OCLN), Zonula occludens 1 (ZO-1), Claudin-5] in blood serum were measured by enzyme-linked immunosorbent assay technique. Biomarker levels in IS patients and SM was compared using the Mann–Whitney U test. Multivariable logistic regression analysis was used to evaluate the diagnostic performance of biomarkers in combination with the National Institutes of Stroke Scale (NIHSS) score. Results: Significant differences in circulating GFAP, NfL, OCLN, ZO-1, and Claudin-5 but not NSE in IS patients compared to SM. The combination of circulating ZO-1, Claudin-5, and OCLN with NIHSS score gives the highest diagnostic accuracy, sensitivity, and specificity. Conclusion: A prediction model with Circulating BBB proteins in combination with NIHSS score differentiates between IS patients and SM.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. This article tries to compel and discuss the most recent information as a way to rename this protein family. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins).

Several noninvasive vascular biomarkers have been suggested for improving the risk stratification for atherothrombotic events. To identify biomarkers suitable for detecting intermediate-risk individuals who might benefit from lipid-lowering treatment (L-LT) in primary prevention, the present study tested the association of plasma LDL-cholesterol with coronary artery calcification (CAC) Agatston score, high carotid and femoral intima-media thickness (IMT), low carotid distensibility and high carotid-femoral pulse-wave velocity in 260 asymptomatic individuals at intermediate cardiovascular risk and free of diabetes and L-LT. High or low vascular biomarkers were considered when their value was above the 95th or below the 5th percentile, respectively, of the distribution in the healthy or in the study population. LDL-cholesterol was independently associated with the CAC score =0 (OR 0.67; 95%CI 0.48-0.92, P=0.01), CAC score >100 (1.59; 1.08-2.39, P=0.01) and with high femoral IMT (1.89; 1.19-3.06, P<0.01), but not with other biomarkers. Our data confirm that in the presence of CAC score =0 in individuals at intermediate risk, L-LT can be avoided, while it should be used in those with CAC score >100. Femoral artery IMT could represent a useful biomarker for decision regarding L-LT, however the reference values according to sex and age should be established in a large healthy population

In order to reconstruct the origin and pathways of variola virus (VARV) dispersion, we analyzed 47 VARV isolates available in public databases and their SNPs. The mean substitution rate of the whole genomes was 9.41x10-6 (95%HPD:8.5-11.3x10-6) substitutions/site/year. The time of the tree root was estimated to be a mean 68 years (95%HPD:60.5–75.9). The phylogeographical analysis showed that the Far East and India were the most probable locations of the tree root and of the inner nodes, respectively, whereas for the outer nodes it corresponded to the sampling locations. The Bayesian Skyline plot showed that the effective number of infections started to grow exponentially in 1915-1920, peaked in the 1940s, and then decreased to zero. Our results suggests that the VARV major strains circulating between 1940s-1970s probably shared a common ancestor originated in the Far East; subsequently moved to India, which became the center of its dispersion to eastern and southern Africa, and then to central Africa and the Middle East, probably following the movements of people between south-eastern Asia and the other places with a common colonial history. These findings may help to explain the controversial reconstructions of the history of VARV obtained using long- and short- term calibrations.

The Regulation (EU) 2016/429 establishes new extensive guidelines for managing transmissible animal diseases, including zoonoses. The Commission Implementing Regulation 2018/1882 classifies diseases into five categories based on their prevalence and the required response, ranging from eradication to surveillance. Key aspects of the regulations concern emphasis on animal traceability, biosecurity, wildlife pathogen control, sustainable farming, and the reduction of the impact of diseases on both public and animal health, as well as on the environment. These align with the European Green Deal, the Farm to Fork Strategy and the One Health approach. In Italian inland areas—similarly to other European regions that are fragile, remote from major service centers, and often neglected—agropastoral and agri-food activities are beneficial for tourism, commercialization of typical foods, and recreational activities. In these areas including the Molise Region, the activation of optional programmes within the framework of the aforementioned regulations could help control infectious animal diseases that are not subject to mandatory eradication but cause income loss and trade restrictions, such as infectious bovine rhinotracheitis and paratuberculosis, a suspected zoonosis potentially linked to Crohn's disease in humans. These programmes could boost the economic income of local extensive breeding, counteract depopulation, and protect human health and the environment.

The increasing diffusion of antimicrobial resistance represents one of the major public health problems worldwide. In the last years, novel antimicrobial molecules have been developed to contrast the emergence of antimicrobial resistance and to provide a valuable therapeutic options against multi drug-resistant (MDR) GNB microorganisms. A new siderophore cephalosporin, Cefiderocol, represents a novel valuable antimicrobial drug for the treatment of infections caused by MDR-GNB. The mechanism of cefiderocol to penetrate trough the outer membrane of bacterial cell with a particular mechanism defined at “Trojan horse” render this molecule unique and immune against the different strategies adopted by GNB to counteract the activity of antimicrobial molecules. The broad spectrum of activity against different GNB species, the potent antibacterial activity, the pharmacokinetics properties, safety, and tolerability render cefiderocol a fundamental drug for the treatment of infections due MDR strains. Although this novel antimicrobial molecule has revolutionized the therapeutic antimicrobial armamentarium against MDR-GNB, the recent emergence of cefiderocol resistant strains have redefined its role in clinical practice and requested novel strategies to preserve its antibacterial activity. In this review, we discuss the mechanism of action of Cefiderocol, emerging resistance mechanisms, pharmacokinetic/pharmacodynamic (PK/PD) properties, efficacy data against the main Gram-negative bacteria, and future prospectives.

This short review is aimed at giving an overview of catalytic carbonylative double cyclization reactions, which are processes in which suitable organic substrates and carbon monoxide are sequentially activated by a promoting catalyst to afford the formation of two new cycles with concomitant incorporation of carbon monoxide as a carbonyl function into the final product. Paradigmatic examples of this powerful synthetic methodology, which allows the one-step synthesis of complex molecular architectures from simple building blocks using the simplest and readily available C-1 unit (CO) are illustrated and discussed. The review is divided into five sections: 1) Introduction; 2) Functionalized Olefinic Substrates; 3) Functionalized Acetylenic Substrates; 4) Functionalized Halides; 5) Conclusions and Future Perspectives.

Endometrial cancer (EC) poses a significant global health challenge, with increasing prevalence in 26 of 43 countries and over 13,000 deaths projected in the United States by 2024. This rise correlates with aging populations, the obesity epidemic, and changing reproductive patterns, including delayed childbearing. Despite the early diagnosis in 67% of cases, approximately 30% of cases present with regional or distant spread, leading to nearly 20% mortality rates. Unlike many cancers, EC mortality rates are escalating, outpacing therapeutic advancements until recently. One of the reasons for this was the lack of effective therapeutic options for advanced disease until recently. The introduction of immunotherapy has marked a turning point in EC treatment, particularly benefiting patients with defects in mismatch repair proteins (dMMRs). However, dMMR status alone does not ensure a favorable response, underscoring the need for precise patient selection. This review explores the pivotal role of mismatch repair proteins in EC, emphasizing their heterogeneity, the challenges in their assessment, and their potential as predictive biomarkers.