Our understanding of the fate and distribution of micro- and nano- plastics in the marine environment and their impact on the biota compartment is limited by the intrinsic difficulties of conventional analytical techniques (light scattering, FT-IR, Raman, optical and electron microscopies) in the detection, quantification and chemical identification of small particles in liquid samples. Here we propose the use of optical tweezers, a technique awarded in 2018 with the Nobel prize, as an analytical tool for the study of micro- and nano- plastics in sea water. In particular, we exploit the combination of optical tweezers with Raman spectroscopy (Raman Tweezers, RTs) to optically trap plastic particles with sizes from tens of µm down to 90 nm and unambiguously reveal their chemical composition. RTs applications are shown on particles made of the most common plastic pollutants, including polyethylene, polypropylene, nylon and polystyrene, that are artificially fragmented and aged directly in seawater. RTs allow us to assess the size and shapes of microparticles (beads, fragments, fibers) and can be applied to investigate particles covered with organic layers. Furthermore, operating at the single particle level, RTs enable unambiguous distinction of plastic particles from marine microorganisms and seawater minerals, overcoming the capacities of standard Raman spectroscopy in liquid, limited to average measurements. Coupled to suitable extraction and concentration protocols, RTs could have a strong impact in the study of the fate of micro and nanoplastics in marine environment, as well as in the understanding of the fragmentation processes on a multi-scale level.

Optical forces are used to aggregate plasmonic nanoparticles and create SERS-active hot spots in liquid. When biomolecules are added to the nanoparticles, high sensitivity SERS detection is accomplished. Here we tailor this methodology to detect catalase and hemoglobin, two Raman resonant biomolecules, at concentrations down to 10 nM and 1 pM. Subsequently, we study the SERS signal in Bovine Serum Albumin as a function of the concentration, finding a monotonic dependence that suggests the possibility of quantitative detection. Finally, by exploiting nanoparticles functionalized with specific aptamers, we obtain first results on the SERS detection of Ochratoxin A, a fungal toxin found in food commodities and wine. This represents a first step towards the addition of molecular specificity to this novel biosensor strategy.

We have studied the very large amount of literary works written by the Italian mystic Maria Valtorta to assess similarities and differences in her writings because she claims that most of them are due to mystical visions. We have used mathematical and statistical tools developed for specifically studying deep linguistic aspects of texts. The general trend indicates that the literary works explicitly attributable to Maria Valtorta differ significantly from her other literary works, that she claims are attributable to the alleged characters Jesus and Mary. Mathematically, they seem to have been written by different authors. The comparison with the Italian literature is very striking. A single author, namely Maria Valtorta, seems to be able to write texts so diverse to cover the entire mathematical range (suitable defined) of the Italian literature of seven centuries.

The aim of this paper is to obtain Karush-Kuhn-Tucker optimality conditions for weakly efficient solutions to vector equilibrium problems with the addition of constraints in the novel context of Hadamard manifolds as opposed to the classical examples of Banach, normed or Hausdorff spaces. More specifically, classical necessary and sufficient conditions for weakly efficient solutions to the constrained vector optimization problem are presented. As well as some examples. The results presented in this paper generalize results obtained by Gong (2008) and Wei and Gong (2010) and Feng and Qiu (2014) from Hausdorff topological vector spaces, real normed spaces and real Banach spaces to Hadamard manifolds, respectively.

The global movement of inputs, raw materials, products, and the marketing of products requires the use of supply chains. Green logistics refers to the set of policies and measures aimed at reducing the environmental impacts generated by logistics activities. The traditional supply chain has a certain inability to adapt to the rules agreed in Coop 15. The Green Supply Chain deals with the distribution flows of goods with a view to generating low environmental impact. The Green Supply Chain (GSC) involves aspects of reducing negative impacts throughout the logistics chain, from raw material suppliers, production to the distribution of the product to the customer. In this way, this article seeks to identify the factors that generate negative impacts in the traditional Supply Chain, thus helping to decarbonize it, and create a path for the development of the GSC and thus avoid interruptions in the distribution flow due to not meeting environmental targets. The main problem in decarbonizing the Supply Chain is its difficulty in complying with the rules agreed by the nations in COOP 15. To this end, a systematic literature review was carried out based on the available literature. Based on various articles and books, the parameters that define a Green Supply Chain and the factors that generate environmental impacts in conventional chains were identified. As a result, it was possible to verify a positive relationship between the carbon emission reduction factors that are linked to the supply chain performance factors found in the literature. Of the factors relating to the decarbonization of supply chains, some were more clearly related, such as reducing carbon emissions, reducing environmental risks and the ability to operate using new technologies. Future research could build on the limitations of this study.

HLA-G is an immune checkpoint molecule with immunosuppressive and anti-inflammatory activities, and its expression and level of its soluble form (sHLA-G) may play an important role in tumor prognosis. The HLA-G 14 bp ins/del polymorphism and the plasma level of soluble HLA-G (sHLA-G) were investigated by a polymerase chain reaction and ELISA, respectively, in 59 glioma patients. A significantly higher proportion of glioma patients had the 14 nt insert in both homozygous and heterozygous states compared to the control group. Glioma patients had also higher plasma levels of sHLA-G. Patients with methylated MGMT promoter had lower levels of sHLA-G than those with unmethylated MGMT promoter. Level of sHLA-G negatively correlated with the overall survival of patients. Glioblastoma patients who survived more than one year after diagnosis had lower levels of sHLA-G than those surviving less than one year. Patients with sHLA-G levels below the cut off value 40 U/mL survived significantly longer than patients with sHLA-G above 40 U/mL. The levels of sHLA-G also negatively correlated with the level of IL-6 (P=0.0004) and positively with IL-10/IL-6 (P=0.046). Conclusion: The presence of 14 nt insert in both homozygous and heterozygous states of the HLA-G 14 bp ins/del polymorphism is more frequent in glioma patients and the elevated plasma levels of sHLA-G are negatively associated with their survival.

Calcium (Ca2+) ions act as second messenger, regulating several cell functions. Mitochondria are critical organelles for the regulation of intracellular Ca2+. Mitochondrial calcium (mtCa2+) uptake is ensured by the presence in the inner mitochondrial membrane (IMM) of the mitochondrial calcium uniporter (MCU) complex, a macromolecular structure composed of pore-forming and regulatory subunits. MtCa2+ uptake plays a crucial role in the regulation of oxidative metabolism and cell death. Many evidences demonstrate that dysregulation of mtCa2+ homeostasis can have serious pathological outcomes. In this review, we briefly discuss the molecular structure and the function of the MCU complex and then we focus our attention on human diseases in which a dysfunction in mtCa2+ has been showed.

In recent years, many libraries and archives have started digitizing their collections thus making maps by Indigenous peoples more easily available for scholars to study. While a number of these maps were discussed by G. Malcolm Lewis in the History of Cartography series (volume 2, book 3, Chapter 4: 1984), more have since been found and disseminated. These maps are critical in understanding the historic and current land tenure of Indigenous groups. Further, Indigenous claims to land can be seen in their connections via toponymy. European concepts of territory and political boundaries did not coincide with First Nation/American Indian views resulting in the mistaken view that Natives did not have formal concepts of their territories. Further, Tribes/First Nations with cross-border territory have special jurisdictional problems. This paper will illustrate how many Native residents were very spatially cognizant of their own lands, as well as neighboring nations’ lands, overlaps between groups, hunting territories, populations, and trade networks. Currently, the Sinixt First Nation provides a perfect example of how an Aboriginal people are inputting and using a GIS representation of their territory with proper toponymy and use areas.

Our understanding of the diversity of life on our planet and the possibility of finding or sustaining life elsewhere in the universe plays a central role in supporting human space settling and exploration. Astrobiology and its outcomes require a multidisciplinary and comprehensive approach, in which the microbial, geological, chemical, astronomical, and physical domains of research are interlinked. An example of the applications of astrobiology and space microbiology is the use of extremophiles for in-situ resource utilization through biomining and bioleaching. To better understand the multidisciplinary research landscape in this area, we have quantitatively reviewed the global scientific literature on astrobiology with a focus on biomining and bioleaching through bibliometric network analysis, investigating patterns and trends in its development over time. The network analysis of the keywords co-occurrence highlights different connecting and overlapping clusters, illustrating the multidisciplinary character of astrobiology. Temporal analyses show a recent focus on topics related to microbiology and geomicrobiology, emphasizing the role that these fields will play in future astrobiology research. In conclusion, astrobiology, biomining, and bioleaching research are timely responding to the identification of these techniques as tools for biotechnological applications, expected to play a crucial role in long-term human space exploration.

Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicles (EVs) effects on immune responses might contribute to improved immunotherapy. EVs derived from Capan-2 and BxPC-3 PC cells isolated by ultracentrifugation were characterized by atomic force microscopy, western blot (WB), nanoparticle tracking analysis and label-free proteomics. Fresh PBMCs from healthy donors were treated with PC- or control-derived heterologous EVs followed by flow cytometry analysis of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated, or -untreated PBMCs was performed and IFN-γ concentration was measured by ELISA. Notably, most of the proteins identified in Capan-2 and BxPC-3 EVs by proteomic analysis were connected in a single functional network (p=1x10-16) and were involved in “Immune System” (FDR: 1.10x10-24 and 3.69x10-19, respectively). Interestingly, treatment of healthy donor-derived PBMCs with Capan-2 EVs, but not with BxPC-3 EVs or heterologous control EVs induced early activation of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated PBMCs was consistent with their activation by Capan-2 EVs, indicating IFN-γ among major upstream regulators, as confirmed by ELISA. Proteomic and functional analyses indicate that PC-EVs have pleiotropic effects, and some may activate early immune response, which might be relevant for the development of highly needed immunotherapeutic strategies in this immune-cold tumor.

Inflammation is an essential protective response against injury or infection. Physiological inflammation eliminates the pathogen, promotes tissue repair and healing. An exaggerated, out of control inflammation, however, can become pathological. Inflammation can generate secondary cell damage, inflame the vessels (endothelitis), activate coagulation processes. Among these pathogenetic factors (cell damage, inflammation, endothelitis, coagulopathies), self-amplification mechanisms can be created, spreading beyond the initial site, up to Multiple Organ Failure (MOF) and host death. If the inflammation does not resolve in a physiological way, the remodeling of the tissues can be maladaptive and lead to the onset of chronic inflammatory degenerative diseases. Diseases such as sepsis, burns, polytrauma, severe forms of influenza or COVID-19, are characterized by a condition of hyperinflammation, associated with a condition of immunosuppression. The initial events triggered by the pathogen (cell damage, interferon response in the case of viruses) ignite the inflammation by activating the inflammasome, the transcription factor NFkB, the release of pro-inflammatory eicosanoids (Prostaglandins, Leukotrienes, Thromboxanes) by neutrophils and macrophages. Hence, the cells of the innate immune system produce pro-inflammatory cytokines. Indeed, the ‘’eicosanoid storm’’ precedes the ‘’cytokine storm’’. Eicosanoids are a group of potent endogenous lipid mediators derived from omega-6 fatty acids Arachidonic Acid (AA). Eicosanoids include a group of molecules with pro-inflammatory (Prostaglandins, Leukotriens) and pro-coagulant (Thromboxanes) action. In addition, Arachidonic Acid (AA) is the source of Lipoxins (LXs). Lipoxins belong to a group of molecules collectively referred to as specialized pro-solving mediators (SPMs) which also include molecules derived from w-3 eicosapentaenoic acid (EPA): Resolvins (ReV-E sieres) and w-3 docohexanoic (DHA): Resolvins D-series (ReV D-series); Protectins (PTs); Maresins (MaRs). SPMs are important for the resolution phase of inflammation to take place properly. Their deficiency could be involved in both acute uncontrolled inflammation and chronic inflammation. The active regulation of the acute inflammatory process, integrating the precursors of Specialized Pro-resolving Mediators (SPMs), such as ⍵-6 and ⍵-3 in balanced ratio, or the SPMs themselves, could be a complementary therapeutic approach useful for taming the "storm of cytokines '' which characterizes exaggerated forms of inflammation. ⍵-3 and ⍵-6 are part of already widely used, readily available, inexpensive and safe supplements. Resolvins have already been included in clinical trials for various other inflammatory diseases (eye diseases, periodontal diseases).

Peritoneal dialysis (PD) is a home-based efficacious modality for replacement of renal function in end-stage kidney failure patients but is still under-prescribed. A major limitation is the durability of the dialytic technique. Continuous exposure of the peritoneum to bioincompatible conventional glucose-based solutions is thought to be the main cause of long-term morpho-functional peritoneal changes eventually resulting in ultrafiltration failure. Poor PD solution biocompatibility is primarily related to the high glucose content, which is not only detrimental to the peritoneal membrane but has many potential metabolic side effects. To improve the clinical outcome and prolong the survival of the treatment, PD-related bioincompatibility urgently needs to be overcome. However, combining dialytic and osmotic efficacy with a satisfactory biocompatible profile proves quite difficult. New approaches targeting the composition of the PD solution include replacement of glucose with other osmotic agents and the addition of cytoprotective or osmo-metabolic compounds. Other strategies include infusion of mesenchymal cells or the administration of orally active agents. In the present article we review the current evidence on efforts to improve the biocompatible and functional performance of PD, focusing on studies performed in vivo (animal models of PD, human subjects on PD).

In a generalized topological space Tg = (Ω, Tg), ordinary interior and ordinary closure operators intg, clg : P (Ω) −→ P (Ω), respectively, are defined in terms of ordinary sets. In order to let these operators be as general and unified a manner as possible, and so to prove as many generalized forms of some of the most important theorems in generalized topological spaces as possible, thereby attaining desirable and interesting results, the present au- thors have defined the notions of generalized interior and generalized closure operators g-Intg, g-Clg : P (Ω) −→ P (Ω), respectively, in terms of a new class of generalized sets which they studied earlier and studied their essen- tial properties and commutativity. The outstanding result to which the study has led to is: g-Intg : P (Ω) −→ P (Ω) is finer (or, larger, stronger) than intg : P (Ω) −→ P (Ω) and g-Clg : P (Ω) −→ P (Ω) is coarser (or, smal ler, weaker) than clg : P (Ω) −→ P (Ω). The elements supporting this fact are reported therein as a source of inspiration for more generalized operations.

Agriculture and farming worldwide are responsible for numerous environmental threats, including degradation of land and water resources depletion. Underlining the dynamic interaction between bio-physical and socio-economic drivers is the key towards a more sustainable land and water management. With regard to a highly developed agricultural area in southern Italy, multi-regression models were developed to interpret the observed inter-annual variability of cropped land. Main drivers related to Common Agricultural Policy support, product market prices, crop yield and irrigation water availability were investigated. The adopted models revealed the different weighs of each driver. The findings reported the role that direct payments played in supporting the extension of irrigated crops, such as processing tomato. Likewise, the models pointed to decoupled payment scheme as the most important driver of change in the crop pattern over the last years.

Morphological and phylogenetic (45S nrDNA+RPB1 gene) analyses of three glomoid spore-producing arbuscular mycorrhizal fungi revealed the presence of two new species be-longing to the genus Glomus in the family Glomeraceae. In the field, Glomus highlandensis sp. nov. was found in a saltmarsh of the Scottish Highlands and in maritime sand dunes of the Baltic Sea in Poland, both saline environments, while G. mongioie sp. nov. originates from the Italian Alps. Phylogenetic placement analysis using environmental sequences indicated that G. highlandensis could have likely worldwide distribution while G. mongioie seems to be a rare species in the world. The molecular and phylogenetic analysis provided important insights about the presence of ribosomal variants in Glomus, with potential negative implication in phylogeny and species recognition.

Fabry disease (FD) is a X-linked inheritable storage disease caused by deficiency of al-pha-galactosidase causing lysosomal overload of sphingolipids. FD cardiomyopathy is character-ized by left ventricular (LV) hypertrophy and should be considered in differential diagnosis with all the other causes of LV hypertrophy. An early diagnosis of FD is very important because the enzyme replacement therapy (ERT) may change the fate of patients by blocking both cardiac and systemic involvement and improving prognosis. Diagnosis may be relatively easy in young patients with the typical signs ans symptoms of FD, but in male patients with late onset of disease and in females, diagnosis may be very challenging. Morphological and functional aspects are not specific for FD, which cannot be diagnosed or excluded by echocardiography. Cardiac magnetic resonance (CMR) with tissue characterization capability, is the preferred technique for the differential diagnosis of LV hypertrophy. The finding of decreased myocardial T1 value in LV hypertrophy is very specific for FD. Late gadolinium enhancement (LGE) is found in late stage of disease but it is useful to predict the cardiac response to ERT and to stratify the prognosis.

In a generalized topological space T_g = (Ω, T_g) (T_g-space), the g-topology T_g : P (Ω) −→ P (Ω) can be characterized in the generalized sense by specifying the generalized open, generalized closed sets (g-T_g-open, g-T_g-closed sets), generalized interior, generalized closure operators g-Intg, g-Cl_g : P (Ω) −→ P (Ω) (g-T_g-interior, g-T_g-closure operators), or generalized derived, generalized coderived operators g-Der_g, g-Cod_g : P (Ω) −→ P (Ω) (g-T_g-derived, g-T_g-coderived operators), respectively. For very many T_g-spaces, the δ^th-iterates g-Der_g^(δ), g-Cod_g^(δ) : P (Ω) −→ P (Ω) of g-Der_g, g-Cod_g : P (Ω) −→ P (Ω), respectively, defined by transfinite recursion on the class of successor ordinals are also themselves g-T_g-derived, g-T_g-coderived operators for new g-topologies in the generalized sense on Ω. Thus, the use of novel definitions of g-T_g-derived, g-T_g-coderived operators g-Der_g, g-Cod_g : P (Ω) −→ P (Ω), respectively, based on a very clever construction, together with their δ^th-iterates g-T_g-operators g-Der_g^(δ), g-Cod_g^(δ) : P (Ω) −→ P (Ω), defined by transfinite recursion on the class of successor ordinals, will give rise to novel generalized g-topologies on Ω. The present authors have been actively engaged in the study of g-T_g-operators in T_g-spaces. The study of the essential properties and the commutativity of novel definitions of g-T_g-interior and g-T_g-closure operators g-Int_g, g-Cl_g : P (Ω) −→ P (Ω), respectively, in T_g has formed the first part, and the study of the essential properties and sets of consistent, independent axioms of novel definitions of g-T_g-exterior and g-T_g-frontier operators g-Ext_g, g-Fr_g : P (Ω) −→ P (Ω), respectively, has formed the second part. In this work, which forms the last part on the theory of g-T_g-operators in T_g-spaces, the present authors propose to present novel definitions and the study of the essential properties of g-T_g-derived and g-T_g-coderived operators g-Der_g, g-Cod_g : P (Ω) −→ P (Ω), respectively, and their δ^th-iterates, and the notions of g-T_g-open and g-T_g-closed sets of ranks δ in T_g-spaces.

The purpose of this paper is to identify factors that influenced customer satisfaction in the Moscow taxi market. The previous researches in customer satisfaction of transportation services laid the foundation of factor model. The resulting list of factors was revised by taxi market experts. The augmented model provided the basis for quantitative survey. The research sample included 310 respondents who have been using taxi services in Moscow during past 2 years. Survey data was analyzed using multiple choice regression method. Analysis results show significant differences between frequent and casual taxi users and a certain number of passenger experience factors that have no influence on customer satisfaction:for frequent users it is discount, for regular users - trip environment, and for rare clients - technical support&security and trip comfort.

In a generalized topological space Tg = (Ω, Tg), generalized interior and generalized closure operators g-Intg, g-Clg : P (Ω) −→ P (Ω), respectively, are merely two of a number of generalized primitive operators which may be employed to topologize the underlying set Ω in the generalized sense. Generalized exterior and generalized frontier operators g-Extg, g-Frg : P (Ω) −→ P (Ω), respectively, are other generalized primitive operators by means of which characterizations of generalized operations under g-Intg, g-Clg : P (Ω) −→ P (Ω) can be given without even realizing generalized interior and generalized closure operations first in order to topologize Ω in the generalized sense. In a recent work, the present authors have defined novel types of generalized interior and generalized closure operators g-Intg, g-Clg : P (Ω) −→ P (Ω), respectively, in Tg and studied their essential properties and commutativity. In this work, they propose to present novel definitions of generalized exterior and generalized frontier operators g-Extg, g-Frg : P (Ω) −→ P (Ω), respectively, a set of consistent, independent axioms after studying their essential properties, and established further characterizations of generalized operations under g-Intg, g-Clg : P (Ω) −→ P (Ω) in Tg.

The present study comprises the second part of our previous work that dealt mainly with the phytochemical and physicochemical characterization of green coffee, clove, cinnamon/clove and nutmeg ethanolic extracts of grape origin. In the present study, we focused on producing a discriminating model concerning green coffee, clove, cinnamon, cinnamon and clove, and nutmeg fine powders based on multivariate analysis of variance and supervised learning on data of volatile compounds analysis, carried out with solid phase dynamic extraction in combination with gas chromatography/mass spectrometry. Results showed that 7 volatile compounds namely ethylene, methanol, 3-methylpentane, ethyl acetate, 9-hexadecen-1-ol, toluene, and methyl acetate could differentiate the investigated samples resulting in a 100% classification rate using the cross-validation method of linear discriminant analysis. Results were further confirmed using partial least squares regression analysis. The study contributes to the typification of green coffee, cinnamon, clove, cinnamon and clove and nutmeg, based on selected volatile compounds, and provides further support to the literature by means of possible adulteration given the statistical models developed.

In a bid to resolve lingering problems in cosmology, more focus is being tilted towards cosmological models in which physical constants of nature are not necessarily real constants, but varying with cosmic time. In this paper we have study cosmology in nonlinear electrodynamics with the Newton's gravitational constant $G$ not a constant but vary in form of power-law of the scale factor of the universe. The evolution of the scale factor $a (t)$ is studied in this model which depends on nonlinear electrodynamics fine tuning term of $\alpha$. Then we check the stability of the model using the speed of sound.

G-quadruplexes are noncanonical nucleic acid structures formed from stacked guanine tetrads. They are frequently used as building blocks and functional elements in fields such as synthetic biology and also thought to play widespread biological roles. G-quadruplexes are often studied as monomers but can also form a variety of higher-order structures. This increases the structural and functional diversity of G-quadruplexes, and recent evidence suggests that it could also be biologically important. In this review we describe the types of multimeric topologies adopted by G-quadruplexes and highlight what is known about their sequence requirements. We also summarize the limited information available about potential biological roles of multimeric G-quadruplexes and suggest new approaches that could facilitate future studies of these structures.

(1) Background: In this work, a series of benzimidazole derivatives containing colchicine-like and cathechol-like moieties with methyl group substitution in the benzimidazole ring were evaluated for their in vitro antiproliferative, pro-apoptotic and antioxidative activity against highly invasive breast cancer cell line MDA-MB-231 and related impairment of tubulin dynamics; (2) Methods: MTT assay was used to evaluate the antiproliferative activity. In vitro tubulin polymerization assay as well as docking analysis was applied to prove the alterations in tubulin polymerization. Immunofluorescent and DAPI staining reveal the pro-apoptotic potential of benzimidazole derivatives and the effect on tubulin’s dynamics in living cells. The antioxidant activity was evaluated by scavenging of H2O2 and hypochlorite ion and ortho-phenanthroline tests; (3) Results: The compounds containing colchicine-like moiety displayed significant growth inhibitory effect against cancer cell line as was highlighted the role of methyl functional group on the tubulin aggregation and blockage of mitosis. All compounds showed an ability to scavenge H2O2, while the compounds with cathecol-like moiety were more effective against hypochlorite ion and chelation of iron; (4) Conclusions: The benzimidazole derivative containing colchicine-like moiety and methyl group substitution in benzimidazole ring is a potential antiproliferative and microtubule destabilizing agent.

COVID-19 disease, caused by the SARS-CoV2 virus, is a potentially fatal disease that represents a serious public health and economic problem worldwide. The SARS-CoV2 virus infects the lower respiratory tract and can cause pneumonia in humans. ARDS is the leading cause of death in COVID-19 disease. One of the main characteristics of ARDS is the cytokine storm, an uncontrolled systemic inflammatory response resulting from the release of pro-inflammatory cytokines and chemokines and growth factors, by immune cells. The other important aspect of the disease is represented by the involvement of the vascular organ that undergoes endothelitis. Hyperinflammation and endothelitis contribute in various ways to trigger coagulation disorders with diffuse micro thrombotic and thromboembolic phenomena. Lastly, multiple organ failure may occur (MOF). Since so far there is no approved treatment, there is an urgent need to reposition known treatments, considered safe, to be included in trials. Naturally produced interferons represent the body's first line of defense against viruses. Pharmacological forms, obtained by means of genetic recombination techniques, have long been approved and used to treat numerous pathologies. Interferons are divided into three families, within which some subfamilies are distinguishable. Only IFN-II comprises a single isoform which has completely different aspects and functions. The IFN I and III, however, each comprise different subfamilies (17 subfamilies the IFN-I and 4 subfamilies the IFN-III), share many aspects, representing the body's first antiviral response, but play different roles. The use of IFNs has been studied in two severe hCoV (Human Coronavirus) diseases, closely related to COVID-19 disease, such as SARS and MERS. Numerous in vitro and in vivo studies have been conducted, often in combination with other antivirals. The results have been controversial. The positive results in vitro and in experimental animals were often not replicable in humans. The possible positioning of these molecules in the right window of therapeutic opportunity requires that the complex dialogue between IFN, inflammasome, cytokines, pro-inflammatory chemokines, growth factors and barrier function be shed light.

Covid-19 disease is caused by SARS Cov-2 virus. Despite its high transmissibility, the CFR (Case Fatality Rate) of COVID-19 seems to be lower than the SARS (9,5%) and MERS (34,4%) ones⁹³ , but higher than the influenza one (0-1%)^94,95 . The disease is asymptomatic or paucisymptomatic in most of the patients, although in few cases it can be characterized by serious complications. The main causes of hospitalization in intensive care are represented by ALI (Acute Lung Injury), ARDS (Acute Respiratory Distress Syndrome), cardiovascular problems and coagulopathies (diffuse thrombosis, microthrombosis, embolisms, myocarditis, arrhytmias, heart failure, stroke)^96-98, acute nephropathy^99,100 and encephalopathies¹⁰¹. The virus presence in the vascular wall can cause endotheliitis, which triggers the process of diffuse coagulation that can lead to a worsening of the systemic inflammation. The exaggerated inflammatory response seems to be connected with the development of ARDS, MOF (Multiple Organ Failure) and coagulopathies^102-107.

We review time expansion wave theory and refine our model showing it to accurately match observed cosmological luminosity data. The theory augments general relativity to create a container within which quantum effects can be explained by treating time as an artefact of a fourth spatial dimension that we observe as the expansion of the universe. This leads us to explain mass creation, the speed of light limit, gravity, black holes without singularities and other macroscopic effects. Our model leads to an expansion velocity of 6.87 0.36 × 106 ms-1, which results in a Hubble expansion rate constant of 71.3 3.7 km/s/Mpc. Because of the finite window of time in which we exist, an extra a degree of freedom is available leading to interesting interpretations at the subatomic level. At this size range, then a spin is allowed within the time dimension explaining why wave particle duality occurs and explains the electromagnetic force and other quantum mechanical properties. It provides a solution to the double slit conundrum and can explain how quantum entangled partners can behave in a quantum way and pass seemingly time-defying information. The potential quantitative origin of the fine structure constant which governs the size of the electromagnetic force is also strongly indicated by this theory.

Resistance to hormone therapy and disease progression is the major challenge in clinical management of prostate cancer (PC). Drugs currently used in PC therapy initially show a potent antitumor effect. Nevertheless, PC gradually develops resistance, relapses and spreads. Most patients develop, indeed, castrate-resistant PC (CRPC), which is almost incurable. The nerve growth factor (NGF) acts on a variety of non-neuronal cells by activating the NGF tyrosine-kinase receptor, TrkA. NGF signaling is deregulated in PC. In androgen-dependent PC cells, TrkA mediates the proliferative action of NGF through its cross talk with the androgen receptor (AR). Epithelial PC cells, however, acquire the ability to express NGF and TrkA, as the disease progresses, indicating a role for NGF/TrkA axis in PC progression and androgen-resistance. We here report that once activated by NGF, TrkA mediates proliferation, invasiveness and epithelial-mesenchyme transition (EMT) in various CRPC cells. NGF promotes organoid growth in 3D models of CRPC cells, and specific inhibition of TrkA impairs all these responses. Thus TrkA represents a new biomarker to target in CRPC.

Heart failure (HF) is a growing issue in developed countries and most patients present with a reduced ejection fraction. This condition significantly impairs quality of life and represents a threat not only for patients, but also for the entire healthcare system due to its high management cost. In the last decade, new medical treatments and devices have been developed to reduce HF hospitalizations and improve prognosis, while reducing the overall mortality rate. Medical therapy does not achieve the same results in all patients and, whenever it fails, technology comes in handy: novel devices for the management of HF have reduced symptoms. They have also improved the treatment of fluid retention and life threatening arrhythmias. The present review article gives to the readers a comprehensive overview of the most recent and important findings that need to be considered in HF with reduced ejection fraction patients. Both novel medical treatments and devices have been presented and discussed.

Recently, a rising use of wireless internet technologies has been demonstrated. The devices 18 which use these technologies emit in new spectral regions an electromagnetic radiation (EMFs) 19 which could interact with the male reproductive system. The aim of this study was to investigate in 20 vitro influence of electromagnetic fields at 27 GHz on sperm quality in Mytilus galloprovincialis. 21 Sperm samples, were collected from sexually mature males of M. galloprovincialis and placed in sea- 22 water. Once evaluated the number and quality of spermatozoa, sperm cells were exposed to elec- 23 tromagnetic fields radiated by a pyramidal horn antenna. The effect of exposure was evaluated after 24 10, 20, 30, 40 and 60 minutes with light microscope and using Eosin test. Ten replications were per- 25 formed for each time series, and statistical analysis was carried out byt-test. A significative decrease 26 in sperm motility was observed after 10 minutes of exposure and after 30 minutes most of sperms 27 were immobile and not vital. This study provides useful data on potential ecological impact of the 28 5G high-band on animal fertility, whose effect is currently under investigation.

Several specific types of generalized compactness of generalized topological spaces have been defined, investigated and related to compactness in ordinary topological spaces from time to time in the literature of topological spaces. Our recent research in the field of a new class of generalized compactness in a generalized topological space is reported herein as a starting point for more generalized classes.

Several specific types of ordinary and generalized connectedness in a generalized topological space have been defined and investigated for various purposes from time to time in the literature of topological spaces. Our recent research in the field of a new type of generalized connectedness in a generalized topological space is reported herein as a starting point for more generalized types.

Several specific types of generalized maps of a generalized topological space have been defined and investigated for various purposes from time to time in the literature of topological spaces. Our recent research in the field of a new class of generalized maps of a generalized topological space is reported herein as a starting point for more generalized classes.

Several specific types of generalized sets of a generalized topological space have been defined and investigated for various purposes from time to time in the literature of topological spaces. Our recent research in the field of a new class of generalized sets of a generalized topological space is reported herein as a starting point for more generalized classes.

This study considers an application of the first-order Grey Markov Model to foresee the values of Italian power generation in relation to the available energy sources. The model is used to fit data from the Italian energy system from 2000 to 2022. The integration of Markovian error introduces a random element to the model, which is able now to capture inherent uncertainties and misalignments between the Grey model predictions and the real data. This application provides valuable insights for strategic planning in the energy sector and future developments. The results show good accuracy of the predictions, which provides powerful information for the effective implementation of energy policies concerning the evolution of energy demand in the country. Despite advancements, Italy’s 2032 energy mix will still significantly rely on fossil fuels, emphasizing the need for sustained efforts beyond 2032 to enhance sustainability.

The G-NUMEN array is the future gamma spectrometer of the NUMEN experiment (Nuclear Matrix Element for the Neutrinoless double beta decay), to be installed around the object point of the MAGNEX magnetic spectrometer at the INFN-LNS laboratory.. This project aims at exploring Double Charge Exchange (DCE) reactions in order to obtain crucial information about the neutrinoless double beta decay (0νββ). The primary objective of the G-NUMEN array is to detect the gamma rays emitted from the de-excitation of the excited states populated via DCE reactions with good energy resolution and detection efficiency, amidst a background composed of transitions from competingreaction channels with far higher cross-sections. To achieve this, the G-NUMEN signalswill be processed in coincidence with those generated by the detection of the reaction ejectiles in the MAGNEX Focal Plane Detector(FPD). Under the expected experimental conditions, G-NUMEN detectors will operate at high counting rates, of the order of hundreds of kHz per detector, while maintaining excellent energy and timing resolutions. The complete array will consist of over 100 LaBr3(Ce) scintillators. Initial tests have been conducted on the first detectors of the array, allowing for the determination of their performance at high rates.

5G technology is evolving to satisfy several service requirements favoring high data-rate connections and lower latency times than current ones (< 1ms). 5G systems use different frequency bands of the radio wave spectrum, taking advantage of higher frequencies than previous mobile radio generations. In order to guarantee a capillary coverage of the territory for high reliability applications, it will be necessary to install a large number of repeaters because higher frequencies waves have a lower capacity to propagate in free space. Following the introduction of this new technology, there has been a growing concern about possible harmful effects on human health. The aim of this study is investigating possible short term effects induced by 5G-millimeter waves on embryonic development of Danio rerio. We have exposed fertilized eggs to 27 GHz frequency, 9.7 mW/cm2 incident power density, 23 dbm and have measured several endpoints every 24 hours. The exposure to electromagnetic fields at 27 GHz (5G) caused no significant impacts on mortality nor on morphology because the exposed larvae showed a normal detachment of the tail, presence of heart-beat and well-organised somites. A weak positivity on exposed larvae has been highlighted by immunohistochemical analysis.

In this study we have investigated the effect of the addition of Nb2O5 (up to 5 mol%) on the structure and luminescent properties of ZnO-B2O3 glass doped with 0.5 mol % Eu2O3 by using of infrared (IR), Raman and photoluminescence (PL) spectroscopy. Physical properties as molar volume, oxygen packing density and glass transition temperature were determined using the results of differential thermal analyisis (DTA) and Archimedes principle for density. IR and Raman spectra revealed that niobium ions incorporate into the base zinc borate glass as NbO4 trtraherda and NbO6 octahedra. A strong red emission from the 5D0 level of Eu3+ ions was registered under near UV (392 nm) excitation using the sharp 7F0 - 5L6 transition of Eu3+. The integrated fluorescence intensity ratio R (5D0 → 7F2/5D0 → 7F1) was calculated to estimate the degree of asymmetry around the active ion, suggesting a location of Eu3+ in non-centrosymmetric sites. The higher Еu3+ luminescence emission observed in zinc borate glasses containing 1÷5 mol% Nb2O5 compared to the Nb2O5-free zinc borate glass evidences that Nb2O5 is suitable component for modification of host glass structure and improving the emission intensity.

Introduction: The trophoblast derived angiogenic factors are considered to play an important role in the pathophysiology of various complications of pregnancy. The aim of this study was to establish relationship between concentrations of soluble Human Leukocyte Antigen-G (sHLA-G) in maternal serum and amniotic fluid at 16-22 weeks of gestation and the sonographic measurements of the fetal and placental growth. Materials and methods: sHLA-G in serum and amniotic fluid, as well as fetal biometric data and placental volume and perfusion indices were determined in 41 uncomplicated singleton pregnancies. Results: The sHLA-G levels were unchanged both in amniotic fluid and in serum during mid-pregnancy. The sHLA-G level in serum correlated positively with amniotic sHLA-G level (β=0.63, p<0.01). Significant correlation was found between serum sHLA-G level and abdominal measurement (β=0.41, p<0.05) and estimated fetal weight (β=0.41, p<0.05). The amniotic sHLA-G level and placental perfusion (VI: β = -0.34, p<0.01 and VFI: β = -0.44, p<0.01, respectively) were negatively interrelated. A low amniotic sHLA-G level was significantly associated with nuchal translucency (r = -0.102, p<0.05). Conclusions: sHLA-G assayed in amniotic fluid might be a potential indicator for placental function, whereas the sHLA-G level in serum can be a prognostic modality for feto-placental insufficiency.

Background Cytomegalovirus (CMV) is a major pathogen that cause remarkable rate of morbidity and mortality, especially in immunocompromised patients. It is important to find risk factors associated with CMV viremia. We studied the differences in CMV seropositivity in relation to liver function biomarkers in male and female Saudi population in an attempt to understand the variation in the CMV seroprevalence with sex and find the risk factor to develop liver dysfunction or hepatocellular carcinoma. Material and subjects: The CMV- IgG and IgM were screened in serum samples of 150 non- A-G hepatities patients with elevation of liver profiles (ALT, AST, ALP and GGT) and categorized as males and females. Samples were collected from different general hospitals and polyclinic in KSA from March 2014 to June 2015. A correlation between CMV seropositivity measured with both antibodies and liver enzymes were tested. Receiver operating characteristics (ROC) analysis and multiple regressions were done for the obtained data. Results: Our study shows that females had much higher IgG and IgM compared to age-matching males. A significant correlation between both antibodies and liver enzymes (AST, ALT) was recorded. Less significant correlation of both IgG and IgM with GGT was also observed. Receiver operating characteristics (ROC) analysis revealed that both IgG and IgM can be used as excellent predictive markers for CMV infection as both recorded 100% specificity and sensitivity together with area under the curve of 1 in males and females. Multiple regression analysis ascertain the correlation between both antibodies as dependent variables and liver enzymes as independent variables with ALT being the most affected enzyme with CMV seropositivity especially in females. Conclusion:he data discussed above This study shows that CMV is capable of initiating and accelerating liver dysfunction in both sexes. The high seroprevalence in females at reproductive age is especially important as they can transmit the virus to their developing fetus. Prevention of CMV infection in young girls 11-14 years old, through counseling on hygiene or possible future vaccination, may lead to a decrease of congenital CMV infections with the concomitant risk of developing liver dysfunction or hepatocellular carcinoma. Keywords: Cytomegalovirus, Alanine transaminase, Aspartate transaminase Alkaline phosphatase, γ-Glutamyltranspeptidase, liver function.

Genetic enhancement of grain production and quality is a priority in wheat breeding projects. In this study, we assessed two key agronomic traits - grain protein content (GPC) and thousand kernel weight (TKW) - across 179 Bulgarian contemporary and historic varieties, and landraces in three growing seasons. Significant phenotypic variation existed for both traits among genotypes and seasons, and no discernible difference was evident between the old and modern accessions. To understand the genetic basis of the traits, we conducted a genome-wide association study with MLM using phenotypic data from the crop seasons, best linear unbiased estimators, genotypic data from the 25K Infinium iSelect array, and a Bonferroni-adjusted p-value. As a result, 776 significant quantitative trait nucleotides (QTNs) organized into quantitative trait loci were discovered, including 25 loci associated with GPC, and 35 loci linked to TKW. Additionally, 14 environmentally stable QTNs were identified for TKW. Certain loci on chromosomes 2A, 3A, and 6B favorably in-fluenced GPC, while the locus on chromosome 6D impacted TKW positively. These loci may reflect novel associations to the two traits. Annotations for proteins involved in the remobilization of carbon and nitrogen from vegetative tissues to developing grain during senescence, as well as in the following buildup of resources required for seed germination, have been found for selected pu-tative candidate genes. These include genes coding for 11S globulin seed storage protein, glutamine synthetase, metalloendopeptidase, components of the ubiquitin/proteasome system, sucrose transporter, alpha-amylase, NAC and bZIP transcription factors. Our findings highlight promising genomic regions for targeted breeding programs aimed at improving grain yield and protein content.

G protein-coupled receptors (GPCRs) are expressed essentially on all cells, facilitating cellular responses to external stimuli, and are involved in nearly every biological process. Several members of this family play significant roles in the regulation of adipogenesis and adipose me-tabolism. However, the expression and functional significance of a vast number of GPCRs in adipose tissue are unknown. We used a high-throughput RT-PCR panel to determine the expres-sion of the entire repertoire of non-sensory GPCRs in mouse white, and brown adipose tissue and assess changes in their expression during adipogenic differentiation of murine adipocyte cell line, 3T3-L1. In addition, the expression of GPCRs in subcutaneous adipose tissues from lean, obese, and diabetic human subjects was evaluated by re-analyzing RNA-sequencing data. We detected a total of 292 and 271 GPCRs in mouse white and brown adipose tissue, respectively. There is a significant overlap in the expression of GPCRs between the two adipose tissue depots but several GPCRs are specifically expressed in one of the two tissue types. Adipogenic differ-entiation of 3T3-L1 cells had a profound impact on the expression of several GPCRs. RNA se-quencing of subcutaneous adipose from healthy human subjects detected 255 GPCRs and obesity significantly changed the expression of several GPCRs in adipose tissue. Finally, we report sev-eral highly expressed GPCRs with no known role in adipose biology whose expression was sig-nificantly altered during adipogenic differentiation and/or in the diseased human subjects. These GPCRs could play an important role in adipose metabolism and serve as a valuable translational resource for obesity and metabolic research.

This paper introduces a new routing and touring service both for outdoor and indoor places of touristic and cultural interest designed to be used in the wider area of ​​Attica, Greece. This service is the result of the work done in OPTORER project and it aspires to offer a range of innovative and thematic routes to several specified points of interest in the selected area of Attica, encouraging the combination of indoors and outdoors routes in a single tour. The aim is to optimize the user experience while promoting specific, user-centric features with safety and social welfare being a priority for every designed tour resulting in enhancing the touristic experience in the area. Using a common smartphone device, as well as common wearable devices (i.e., smartwatches), the OPTORER service will provide an end-to-end solution by developing the algorithms and end-user applications, together with an orchestration platform responsible for managing, operating and executing the service that produces and presents to the end user results derived from solving dynamically complex optimization problems.

Several specific types of ordinary and generalized separation axioms of a generalized topological space have been defined and investigated for various purposes from time to time in the literature of topological spaces. Our recent research in the field of a new class of generalized separation axioms of a generalized topological space is reported herein as a starting point for more generalized classes.

The present study is aimed to determine the predicting role of objective (lifestyle) and subjective factors of middle-aged women’s psycho-emotional health such as their attitude towards parents, attachment and separation types. Women who are overloaded with professional and family roles have high stress level, their indicators of psychological well-being and emotional level decrease when they have to give everyday care to their elderly parents. (2) Methods: Sample consists of 146 women aged 38 to 56 ( =41.1, ó=3.5), married (70.5%) and divorced (29.5%), having children of 14-28 years old; giving everyday care to elderly parents for more than 1.5 yrs. Some live separately (62.3 %), or have to cohabitate with parents (37.7%). All women evaluate their life situation as difficult and manifest signs of high psycho-emotional stress. We used methods adapted for the Russian-speaking sample: getting socio-demographic information, an interview; Attachment style and Interpersonal Guilt Questionnaires (study 1); Psychological Separation Inventory, Purpose-in-Life Test, projective methods of incomplete sentences and metaphors` analysis (study 2), mathematical statistics. (3) Results: A number of factors and indicators of women`s psycho-emotional health decrease in the situation of role overload have been identified. Among the factors there are four main types of women’s attitudes towards parents: strong (anxious), distancing, ambivalent, normative closeness, predicting low indicators of psycho-emotional health: dependence on the others` opinions and feedbacks in making decisions, a lack of meaningfulness of life; reduced sense of control over life are showing the decrease. Anxiety about future and neurotic symptoms (increased demands on oneself, irritability, reduced emotional background) distinguish these respondents. (4) Conclusions: The study confirms that middle-aged Russian women`s psycho-emotional health depends on contextual factors (difficult role-overloaded lifestyle) and factors integrating women`s attitudes towards parents, attachment and separation types. Among the most important risk factors there are a difficult life situation, conflict separation type and gilt.

The p53 tumor suppressor protein shows antiviral activity. The replication of viruses is also antagonized by interferons (IFNs) – cytokines, which control immunity genes by the STAT transcription factors. The best studied interferons belong to type I (e.g. IFNα) and type II (IFNγ) groups. IFNα and IFNγ both induce activating phosphorylation of STAT1 on Tyr701. Previously, we noticed that p53 activates SOCS1, which is a negative regulator of STAT1 phosphorylation. Thus, we hypothesized that p53 by activating SOCS1 expression reduces phosphorylation of STAT1 and attenuates activation of genes stimulated either by IFNα or IFNγ. To test this hypothesis, we exposed p53-proficient and p53-deficient cells to strong p53 activators, and either to IFNα or IFNγ. Subsequently, we estimated the phosphorylation status of STAT1 and the expression of genes regulated by either of these cytokines. Strong activation of p53 reduced the phosphorylation of STAT1 on Tyr701, however surprisingly it did not lead to reduced expression of most tested interferon-stimulated genes. On contrary, p53 and IFNγ synergized in the activation of CASP1, IFIT1 and IFIT3 genes. We conclude that the interactions between p53 and interferon-activated pathways are more complicated than initially expected, but the apparent cooperation between p53 and IFNγ deserves further studies.

Immunoglobulin G (IgG) adopts a modular multidomain structure that mediates antigen recognition and effector functions, such as complement-dependent cytotoxicity. IgG molecules are self-assembled into a hexameric ring on antigen-containing membranes, recruiting the complement component, C1q. To provide deeper insights into the initial step of the complement pathway, we report a high-speed atomic force microscopy study for quantitative visualization of the interaction between IgG and the C1 complex composed of C1q, C1r, and C1s. Results showed that C1q in the C1 complex is restricted regarding internal motion and has a stronger binding affinity for on-membrane IgG assemblages than C1q alone, presumably because of smaller conformational entropy loss upon binding. Furthermore, we visualized a 1:1 stoichiometric interaction between C1/C1q and an IgG variant that lacks the entire CH1 domain in the absence of antigen. In addition to the canonical C1q-binding site on Fc, their interactions are mediated through a secondary site on the CL domain that is cryptic in the presence of the CH1 domain. Our findings offer clues for novel-modality therapeutic antibodies.

Human oncoviruses are able to subvert telomerase function in cancer cells through multiple strategies. The activity of the catalytic subunit of telomerase (TERT) is commonly enhanced in virus-related cancers. Viral oncoproteins, such as high-risk human papillomavirus (HPV) E6, Epstein-Barr virus (EBV) LMP1, Kaposi sarcoma-associated herpesvirus (HHV-8) LANA, hepatitis B virus (HBV) HBVx, hepatitis C virus (HCV) core protein and human T-cell leukemia virus-1 (HTLV-1) tax protein, interact with regulatory elements in the infected cells and contribute to the transcriptional activation of TERT gene. Specifically, viral oncoproteins have been shown to bind TERT promoter, to induce post-transcriptional alterations of TERT mRNA and to cause epigenetic modifications, which have important effects on the regulation of telomeric and extra-telomeric functions of the telomerase. Other viruses, such as herpesviruses, operate by integrating their genomes within the telomeres or by inducing alternative lengthening of telomeres (ALT) in non-ALT cells. In this review, we recapitulate recent findings on virus-telomerase/telomeres interplay and the importance of TERT-related oncogenic pathways activated by cancer causing viruses.

Mercury has a strong environmental impact since both its organic and inorganic forms are toxic and it represents a pollutant of global concern. Liquid Hg is highly volatile and it can be released during natural and anthropogenic processes in the hydrosphere, biosphere and atmosphere. In this study the distribution of Gaseous Elemental Mercury (GEM) and the total and leached mercury concentrations on paints, plasters, roof tiles, concretes, metals, dust and wood structures were determined in the main buildings and structures of the former Hg-mining area of Abbadia San Salvatore (Siena, Central Italy). The mining complex (divided into 7 units) covers a surface of about 65 ha and contains mining structures and managers and workers buildings. In this work, nine surveys of GEM measurements were carried out from July 2011 to August 2015 for the buildings and structures located in the units 2, 3 and 6. Moreover, detailed measurements were performed in February, April, July, September and December 2016 in the edifices and mining structures of Unit 6. GEM concentrations showed a strong variability in terms of space and time mostly depending on the distance from the building hosting driers, furnaces and condensers and ambient temperature, respectively. In the Unit 2 surveys carried out in the hotter period (from June to September) showed GEM concentrations up to 27,500 ng m⁻³, while in the Unit 6 they were on average much higher and occasionally they saturated the GEM measurement device (>50,000 ng m⁻³). Concentrations of total (in mg kg⁻¹) and leached (in μg L⁻¹) mercury measured in different building materials (up to 46,580 mg kg⁻¹ and 4,470 mg L⁻¹ for total and leached mercury, respectively) showed for the same type of material highly variable values in dependence on the edifice or mining structure from which they were collected. The results obtained in this study are of relevant interest for the operational cleanings to be carried out during the reclamation activities.

By combining general relativity and CPT symmetry, the theory of CPT gravity predicts gravitational repulsion between matter and CPT-transformed matter, i.e. antimatter inhabiting an inverted space-time. Such repulsive gravity turned out to be an excellent candidate for explaining the accelerated expansion of the Universe, without the need for dark energy. The recent results of the ALPHA-g experiment, which show gravitational attraction between antihydrogen atoms and the Earth, seem to undermine this success in the cosmological field. Analyzing the above theory, we find two solutions that can be consistent with the experimental results, while preserving the large-scale gravitational repulsion. The first highlights how repulsive gravity can be the result of the interaction with an inverted space-time, but occupied by matter and not antimatter, and therefore the antimatter present in our space-time has no reason to exhibit gravitational repulsion. The second retains the original CPT transformation, resulting in repulsive gravity between matter and antimatter, but with the caveat that antimatter immersed in our space-time cannot exhibit the PT transformation which is the cause of the repulsion. Finally, it is shown that, in a Newtonian approximation of the geodesic equation, time reversal is not a necessary operation for repulsive gravity, therefore opening the possibility of an expanding cosmos with a single time direction.

The spin magnetic moments and spin g factors (g_s = -2) of electron, muon and tau are explained based on the electric charges (EC) and lepton charges (LC) in terms of the three-dimensional quantized space model. The spin g factors of electron, muon and tau are g_s = -2 which is the sum of the EC g factor (g_EC = -1) and the LC g factor (g_LC = -1). The spin g factor (g_s = -2) of the electron is predicted by the Dirac’s equation. The orbit g factors of electron, muon and tau are g_L = g_EC = -1 from the EC g factor (g_EC = -1) without the contribution of the LC g factor (g_LC = -1). The spin g factors of the elementary fermions are calculated from the equation of g_s = g_EC + g_LC + g_CC where g_EC = EC/|EC|, g_LC = LC/|LC| and g_CC = CC/|CC|. For example, the spin g factors of the neutrinos and dark matters are g_s = -1. The spin g factors of the u and d quarks are g_s = 0 and g_s = -2, respectively. The g factor problem of neutrinos with the non-zero LC charges are solved by the LC Coulomb force of F_c(LC) ≈0. It is, for the first time, proposed that the binary motion (fluctuations) of the m_EC and m_LC masses for the electron, muon and tau leptons make the anomalous g factor. This binary motion could be originated from the virtual particle processes including the photons. Also, the weak force (beta) decay is closely related to the binary motion of the m_EC and m_LC for the electron, muon and tau leptons.

The G-protein-coupled estrogen receptor (GPER; G protein-coupled estrogen receptor 30, also known as GPR30) is a novel estrogen receptor and has emerged as a promising target for ovarian cancer. GPER, a seven-transmembrane receptor, suppresses cellular viability and migration in studied ovarian cancer cells. However, its impact on the fallopian tube, which is the potential origin of high-grade serous (HGSC) ovarian cancer, has not been addressed. This study was conducted to evaluate the relationship of GPER, ovarian cancer subtypes, i.e., high-grade serous cell lines (OV90 and OVCAR420), as well as potential HGSC ovarian cancer origin (i.e., the fallopian tube cell line FT190). The selective ligand assessed here is the agonist G-1, which was utilized in an in vitro study to characterize its effects on cellular viability and migration. As a result, this study has addressed the effect of a specific GPER antagonist in combination with an agonist on cell viability, providing a better understanding of the effects of these compounds on our diverse group of studied cell lines. Strikingly, attenuated cell proliferation and migration behaviors were observed in the presence of G-1. Thus, our in vitro study reveals the impact of the origin of HGSC ovarian cancers and highlights the GPER agonist G-1 as a potential therapy for ovarian cancer.

Mobile robots need an environmental perception ability in order to interact with the surrounding environment. In this paper we present the G-SLAM method, where the map is consisted of a cloud of scattered points in the continuous space and each point is accompanied by an obstacle existence probability. On the other hand the robot's pose (and trajectory) is estimated by an particle filters while the cloud of points is estimated by an adaptive recursive algorithm which is presented. Main feature of the presented method is the adaptive repositioning of the scattered points and their convergence around obstacles. In addition to our previous publications, In this paper a mathematical derivation of the method is presented and real case scenarios are discussed, presented and compared with other methods.

Calcium sulphate (CS) is currently used as a bioabsorbable, completely synthetic and sterile material in the management of infected tissues and dead spaces (DS) mainly resulting from surgical procedures. Residual DS in the postoperative, may create an environment where hematomas fill up and bacteria can proliferate, leading to a high incidence of postoperative infections. Considering the available reviews in the literature, CS has been mainly studied in orthopedic surgery mostly giving brilliant results and low complication rates. Nowadays, orthopedists avail it in the form of pearls both as a bone void filler and as an “off-label” delivery agent for antibiotics in arthroplasty, chronic osteomyelitis and open fractures, paving the way of its application in many other contexts given its natural dis-position to biodegradation. In the last years, CS beads have been gaining ground in the general, vascular and endocrinological surgical specialties. Despite its clear potential and the increasing number of scientific evidences on the safety and effectiveness of CS application in the prophylaxis and treatment of infections, there are not many studies reporting on its application in fields other than orthopedics, with a substantial paucity in plastic and reconstructive surgery literature. This is some-how surprising, since reconstructive surgery often deals with complex wounds secondary to bone and soft tissue exposure, suture dehiscence, trauma, and surgical site infections. As far as we know this is the first updated systematic review assessing the state of the art, indications and new perspectives on the application of CS beads in plastic and reconstructive surgery.

Antibiotic resistance is a persistent and growing concern. Our objective was to analyze antibiotic prescribing in the United States (US) in the Medical Expenditure Panel System (MEPS) and to Medicaid patients. We obtained total MEPS prescriptions for eight antibiotics from 2013 to 2020. We extracted prescribing rates per 1,000 Medicaid enrollees for two years, 2018 and 2019, for four broad spectrum (azithromycin, ciprofloxacin, levofloxacin, and moxifloxacin) and four narrow spectrum (amoxicillin, cephalexin, doxycycline, and trimethoprim/sulfamethoxazole) antibiotics. Antibiotics in MEPS decreased from 2013 to 2020 by -38.7% with a larger decline for broad (-53.7%) than narrow (-23.5%) spectrum. Antibiotic prescriptions in Medicaid decreased by -6.7%. Amoxicillin was the predominant antibiotic followed by azithromycin, cephalexin, trimethoprim/sulfamethoxazole, doxycycline, ciprofloxacin, levofloxacin, and moxifloxacin. Substantial geographic variation in antibiotic prescribing existed with 2.8-fold between the highest (Kentucky = 855/1,000) and lowest (Oregon = 299) states. The South prescribed 52.2% more antibiotics (580/1,000) than the West (381/1,000). There were significant correlations across states in antibiotic prescribing. This study identified sizable disparities by geography in prescribing rates of eight antibiotics with over three-fold state level differences. Areas with high antibiotic prescribing rates, particularly for outpatients, may benefit from stewardship programs to reduce potentially unnecessary prescribing.

In this study, 10%PTFE/PEEK blend were modified by potassium titanate whisker (PTW) and chopped glass fiber (GF), respectively. The blends were prepared by three-screw extruder. Through the investigation of thermal stability, tribological properties, mechanical properties and rheological behavior, the effects of reinforcing agents were determined. The results illustrated that the mechanical properties of 10%PTFE/PEEK blend can be dramatically improved by adding reinforcing agent of PTW or GF, and the reinforcing effect of GF was especially obvious. As for tribological properties, 1% addition was the best proportion. The friction coefficient and wear rate of the blend with 1% PTW were 0.283 and 4.97 × 10^-6 mm³/N · m, which decreased by 7.2% and 21% compared with those of the blend without reinforcing agent.

The meridian line is a basic instrument for positional astronomy, it was used to study the motion of Sun, Moon, planets and the position of stars by measuring position and time of their passage through the meridian plane. The accuracy of such positions was dependent on precise theories of the atmospheric refraction (Cassini, 1655 and Laplace, 1825) and by the use of reference marks present originally on the meridian line, and now cancelled by the centuries. From October 27, 2018 the new pinhole of the meridian line in the Basilica of S. Maria degli Angeli in Rome (1702) is a circle 25 mm wide and 6.11 mm thick and its position is fixed, in order to perform a series of observations of astrometric quality, the IGEA campaign. The comparison of the observed positions of the meridian passages of the Sun, Southern and Northern limbs, with the ephemerides of Calsky.org and Stellarium 0.20.2 for the Sun are examined for the dates of the ingresses into the zodiacal signs, when the ecliptic longitude is exactly 0°/180° (Aries and Libra, spring and fall equinox), 30°/150° (Taurus, Virgo), 60°/120° (Gemini, Leo), 90° (Cancer), 330°/210° (Pisces, Scorpio), 300°/240° (Aquarius/Sagittarius), 270° (Capricorn). The former geometrical calibration of the marks present on the line, with a total station, is compared with another calibration done with a metal and laser meter. The first star on the floor of the Basilica representing the position of the Sun on August 20, 1702 when the pope Clement XI visited the meridian line, financed by him, has been calibrated with the solar image. The present pinhole is 4.4±0.1 mm South with respect to the original one of 1702.

Amyotrophic Lateral Sclerosis (ALS) is an irreversible neurodegenerative disease with no known cure. Recent studies suggest a strong metabolic component in ALS pathogenesis and have shown an inverse relationship between leptin levels and ALS progression, although the effects of leptin as a treatment have not yet been studied. Therefore, we aim to examine whether the acute treatment with leptin has beneficial effects on brain pathology and cognitive function in the transgenic TDP43A315T line of ALS. Mice were treated intranasally (IN) with 0.03mg/kg of leptin or vehicle (VH) daily for 7 days. Data showed a progressive decline in body weight and motor coordination in TDP43A315T mice. Moreover, Lep-treated TDP43A315T mice showed an earlier disease onset, along with an improvement in motor performance. Altered levels of some of the adipokines and metabolic proteins studied were found in TDP43A315T mice, which were differently expressed among Lep-treated and VH-treated animals. Furthermore, some correlations were found among the serum levels of this proteins in WT and TDP43A315T mice. As far as we know, this is the first pilot study to provide evidence of the therapeutic effect of leptin treatment in a mice model of ALS, although further studies are needed to expound on the underlying mechanisms.

Materials engineering based on metal oxides for manipulating the solar spectrum and producing solar energy have been under intense investigation over the last years. In this work, we present NiO thin films double-doped with niobium (Nb) and nitrogen (N) as cation and anion dopants (NiO:(Nb,N)) to be used as p-type layers in all oxide transparent solar cells. The films were grown by sputtering a composite Ni-Nb target on room-temperature substrates in plasma containing 50% Ar, 25% O2 and 25% N2 gases. The existence of Nb and N dopants in the NiO structure was confirmed by the Energy Dispersive X-Ray and X-Ray Photoelectron Spectroscopy techniques. The nominally undoped NiO film, which was deposited by sputtering a Ni target and used as the reference film, was oxygen-rich, single-phase cubic NiO, having a visible transmittance of less than 20%. Upon double doping with Nb and N the visible transmittance of NiO:(Nb,N) film increased to 60%, which was further improved after thermal treatment to around 85%. The respective values of the direct band gap in the undoped and double-doped films were 3.28 eV and 3.73 eV just after deposition and 3.67 eV and 3.76 eV after thermal treatment. The changes in the properties of the films such as structural disorder, direct and indirect energy band gaps, Urbach tail states and resistivity were correlated with the incorporation of Nb and N in their structure. The thermally treated NiO:(Nb,N) film was used to form a diode with a spin-coated two-layer, mesoporous on top of a compact, TiO2 film. The NiO:(Nb,N)/TiO2 heterojunction exhibited visible transparency of around 80%, showed rectifying characteristics and the diode’s parameters were deduced using the I-V method. The diode revealed photovoltaic behavior upon illumination with UV light exhibiting a short circuit current density of 0.2 mA/cm2 and open-circuit voltage of 500 mV. Improvements of the output characteristics of the NiO:(Nb,N)/TiO2 UV-photovoltaic by proper engineering of the individual layers and device processing procedures are addressed. Transparent NiO:(Nb,N) films can be potential candidates in all-oxide ultraviolet photovoltaics for tandem solar cells, smart windows and other optoelectronic devices.

In this paper, we investigate some kind of Dynkin game under $g$-expectation induced by backward stochastic differential equation (shortly for BSDE). We define the lower and upper value functions $\underline{V}_t=ess\sup\limits_{\tau\in{\mathcal{T}_t}} ess\inf\limits_{\sigma\in{\mathcal{T}_t}}\mathcal{E}^g_t[R(\tau,\sigma)]$ and $\overline{V}_t=ess\inf\limits_{\sigma\in{\mathcal{T}_t}}ess\sup\limits_{\tau\in{\mathcal{T}_t}}\mathcal{E}^g_t[R(\tau,\sigma)]$, respectively. Under some regular assumptions, a pair of saddle point is obtained and the value function of Dynkin game $V(t)=\underline{V}_t=\overline{V}_t$ follows. Furthermore, the constrained case of Dynkin game is also considered.

G protein-coupled receptors (GPCRs) comprise the largest family of membrane receptors that control many cellular processes and consequently often serve as drug targets. These receptors undergo a strict regulation by mechanisms such as internalization and desensitization, which are strongly influenced by posttranslational modifications. Ubiquitination is a posttranslational modification with a broad range of functions that is currently gaining increased appreciation as a regulator of GPCR activity. The role of ubiquitination in directing GPCRs for lysosomal degradation has already been well-established. Furthermore, this modification can also play a role in targeting membrane and endoplasmic reticulum-associated receptors to the proteasome. Most recently, ubiquitination was also shown to be involved in GPCR signaling. In this review, we present current knowledge on the molecular basis of GPCR regulation by ubiquitination, and highlight the importance of E3 ubiquitin ligases, deubiquitinating enzymes and β-arrestins. Finally, we discuss classical and newly-discovered functions of ubiquitination in controlling GPCR activity.

Analyses of the three predominant types of sedimentation – clastic, carbonate and black shale – revealed their discontinuity/continuity in different facies environments of the Middle and Late Devonian of the central part of the Volga-Urals petroleum province, namely (1) in depressions, both condensed and non-condensed, (2) on the slopes of depressions and (3) in shallow water environments represented by tectonic arches or localised biohermal uplifts. The regional zonation of conodonts, correlated with the global chronostratigraphic scheme, substantiates the stratigraphic completeness of the general Devonian sequence in this area. In particular, the sedimentation of organic-rich black shales, traditionally considered as source rocks, lasted more than 29 million years, starting from the Late Eifel and ending at the Devonian-Carboniferous boundary. There was only one hiatus in the deposition of both black shales and carbonate sediments, lasting about 2.5 million years at the end of the Frasnian. That interval is dominated by clastic sediments, which are considered to be the most productive reservoirs of the Volga-Ural province. In the time interval from the beginning of the Eifel to the end of the Frasnian (about 17 Ma), (a) clastic sediments show the highest accumulation rates; (b) the most complete sequences occur in depressions; and (c) arches and uplifts show the most significant gaps in the geological record. During Famennian, (a) clastic sedimentation has completely ceased; (b) differences between the slopes of troughs and shallow-water environments have diminished, resulting in stable accumulation of carbonate sediments in both settings; (c) the decrease in sequence thickness (up to 50 m) in depressions suggests reduced accumulation rates of deep-water organic-rich black shales. The results help to understand the complex spatial relationship between different coexisting sedimentation types and focus attention to the incompleteness of the geological record in different environments.

Background: The validation of laser usage during laparoscopic procedures, notably by Camran Nezhat in the late 1980s, has been significant. Lasers offer precision and depth control in tissue vaporization without bleeding. Surgical intervention remains central in managing endometrio-sis-associated pain and infertility, especially for patients unresponsive to hormonal therapy. Methods: This retrospective cohort study included 200 patients with SPE who underwent laparo-scopic laser vaporization. Surgery was performed using a CO2 laser, and histological confirma-tion of endometriosis was obtained for all cases. Pain scores and SF-36 questionnaire domains were assessed preoperatively and postoperatively. Fertility outcomes were evaluated among pa-tients desiring pregnancy. Results: Significant improvements in pain score and SF-36 questionnaire domains were ob-served postoperatively (p-value

Rapid emergence of evasive SARS-CoV-2 variants is an on-going challenge for COVID-19 vaccinology. Traditional virus neutralization tests provide detailed datasets of neutralization titers against the viral variants. Such datasets are difficult to interpret and do not immediately inform on the sufficiency of the breadth of antibody response. Some of these issues could be tackled using the antigenic cartography approach. In this study, we created antigenic maps using neutralization titers of sera from donors who received Sputnik V booster vaccine after primary Sputnik V vaccination and compared them with the antigenic maps based on serum neutralization titers of Comirnaty-boosted donors. Traditional analysis of neutralization titers against WT, Alpha, Beta, Delta, Omicron BA.1 and BA.4/BA.5 showed a significant booster humoral response after both homologous (Sputnik V) and heterologous (Comirnaty) revaccinations against all the studied viral variants. However, despite this, a more in-depth analysis using antigenic cartography revealed that Omicron variants remain antigenically distant from WT, which is indicative of the formation of insufficient levels of cross-neutralizing antibodies. The implications of these findings may be significant when developing a new vaccine regimen.

Generally, stochastic functional differential equations (SFDEs) pose a challenge as they often lack explicit exact solutions. Consequently, it becomes necessary to seek certain favorable conditions under which numerical solutions can converge towards the exact solutions. This article aims to delve into the convergence analysis of solutions for stochastic functional differential equations by employing the framework of G-Brownian motion. To establish the goal, we find a set of useful monotone type conditions and work within the space Cr((−∞,0];Rn). The investigation conducted in this article confirms the mean square boundedness of solutions. Furthermore, this study enables us to compute both LG2 and exponential estimates.

G-protein-coupled receptors (GPCRs) are ubiquitous sensors and regulators of cellular functions. Each GPCR exists in complex aggregates with multiple resting and active conformations. Designed to detect weak stimuli, GPCRs can also activate spontaneously, resulting in basal ligand-free signaling. Agonists trigger a cascade of events leading to an activate agonist-receptor-G protein complex with high agonist affinity. However, the ensuing signaling process can further remodel the receptor complex to reduce agonist affinity, causing rapid ligand dissociation. The acutely activated ligand-free receptor can continue signaling, as proposed for rhodopsin and  opioid receptors, resulting in robust receptor activation at low agonist occupancy with enhanced agonist potency. Continued receptor stimulation can further modify the receptor complex, regulating sustained ligand-free signaling - proposed to play a role in opioid dependence. Basal, acutely agonist-triggered, and sustained elevated ligand-free signaling could each have distinct functions, reflecting multi-state conformations of GPCRs. This review addresses basal and stimulus-activated ligand-free signaling, its regulation, genetic factors, and pharmacological implications, focusing on opioid and serotonin receptors, and the growth hormone secretagogue receptor (GHSR). Ligand-free signaling of intracellular 5-HT2A receptors could mediate therapeutic effects of psychedelic drugs. Research avenues are suggested to close gaps in our knowledge of ligand-free GPCR signaling.

The p53 tumor suppressor protein is an activator of transcription. Diverse stress factors lead to various sets of posttranslational modifications of p53 what results in different sets of upregulat-ed genes. We noticed that actinomycin D and nutlin-3a (A+N) synergize in inducing activating phosphorylations of p53 and upregulation of selected p53-target genes. Here we found that one of these genes is DUSP13, which codes for poorly-studied, dual-specificity phosphatase having at least two isoforms, one expressed in testis and the other in skeletal muscles. In cancer cells ex-posed to A+N, DUSP13 is expressed from an alternative promoter in intron, what results in ex-pression of isoform named TMDP-L1. The luciferase reporter tests demonstrated that this pro-moter is activated by both endogenous and ectopically expressed p53. We showed for the first time that mRNA expressed from this promoter actually produces the protein, which can be de-tected by Western blotting in all examined cancer cell lines with wild-type p53 exposed to A+N. In some cell lines it is also induced by clinically relevant camptothecin or by nutlin-3a acting alone. This isoform, fused with green fluorescent protein localizes in perinuclear region of cells. Thus, TMDP-L1 isoform may be an important element of p53-regulated stress response system.

Treatment of osteochondritis dissecans of the knee, has always been a challenge for orthopedic surgeons. We present a case report of a 38-year-old male with severe right knee pain after suffering from an indirect trauma and axial rotation of the knee, limiting knee functionality and impeding ability to walk, with diagnosis of osteochondritis dissecans in the trochlea of the knee, who underwent arthroscopic treatment with matrix induced autologous chondrocyte implantation (MACI). After the surgery, physical therapy protocol for MACI was implemented, magnetic imagen resonance images with cartilage mapping were used to evaluate recovery of the lesion. A total recovery was observed evaluated with the modified Cincinnati knee rating system (mCKRS). A discussion is provided with evidence and general recommendations for the use of MACI in the treatment of adult OCD of the knee.

Articular cartilage injuries are found in up to 60 % of patients who undergo an arthroscopic knee procedure, those that totally affect articular cartilage (grade IV) have limited regenerative capac-ity and extended time for recovery, 3-D scaffolds represent a novel solution to address this type of injury. Our purpose was to analyze MRI findings and functional status of patients that underwent repair of chondral defects either by microfractures or Hyaluronan (HA) 3-D Scaffold. We con-ducted a retrospective study of patients with chondral defects. The outcomes analyzed in this study included anatomical changes envaulted by the Henderson score (based on MRI findings) at baseline, 6, and 12 months after surgery; and improvement in functionality, evaluated by the Modified Cincinnati Knee Rating System (MCKRS) at baseline and 6 months after surgery. Clini-cal and demographic characteristics were similar for both groups. There was a statistically sig-nificant improvement in Henderson score for the 3-D scaffolding treated group at 6 months, ver-sus the microfracture group (p < 0.0001). Improvement in functionality, measured by MCKRS was more frequently found in the 3-D scaffold treated group. In conclusion the use of HA 3-D scaf-folding was superior with faster recovery, evident after 6 months of the surgery, that progress to full recovery in all patients after a year of surgery. Future studies with a randomized design might help to sustain our findings. This study provides a level III of evidence.

Octyl methoxycinnamate (OMC) is a common UVA and UVB filter molecule that is widely used is commercial sunscreens. Here, we use gas-phase laser photodissociation spectroscopy to characterize the intrinsic photostability and photodegration products of OMC, by studying the system as its protonated form, i.e. [OMC·H]+. The major photofragments observed have, m/z 179, 161, and 133, corresponding to fragmentation on either side of the of the ether oxygen of the ester group (m/z 179, and 161) or the C-C bond adjacent to the ester carbonyl group. Additional measurements were obtained using higher-energy collisional dissociation mass spectrometry (HCD-MS), to identify fragments which result from breakdown of the vibrationally hot electronic ground state. We found that the m/z 179 and 161 ions are the main fragments produced by this route. Notably, the m/z 133 ion was not observed through HCD-MS, revealing that this product ion is only produced through a photochemical route. Our results demonstrate that UV photoexcitation of OMC is able to access a dissociative excited state surface that uniquely leads to rupture of the C-C bond adjacent to the key ester carbonyl group.

The efficacy of weed management depends on the correct control timing according to the seedling emergence dynamics. Since soil temperature and soil moisture are two main factors that determine weed germination, the hydrothermal time model can be used to predict their emergence. The aim of this study was to estimate the base temperature (Tb) and base water potential (Ψb) for germination of Chenopodium album, Amaranthus retroflexus, Setaria pumila and Panicum capillare collected from fields in continental Croatia and then to compare these values with those of Italian populations embedded in the AlertInf model. Germination tests were performed at seven constant temperatures (ranging from 4 to 27°C) and eight water potentials (0.00 to - 1.00 MPa). Estimated Tb and Ψb were 3.4°C, -1.38 MPa for C. album, 13.9°C, -0.36 MPa for A. retroflexus, 6.6°C, -0.71 MPa for S. pumila and 11.0°C, -0.87 MPa for P. capillare, respectively. According to the criterion of overlap of the 95% confidence intervals, only Tb of C. album, and Ψb of A. retroflexus were similar between Croatian and Italian populations. Further field experiments should be conducted in the Croatian field to monitor weed emergence patterns of C. album and to calibrate the AlerInf equation parameters.

Polymeric particles made up of biodegradable and biocompatible polymers such as poly(lactic-co-glycolic acid) (PLGA) are promising tools for several biomedical applications including drug delivery. Particular emphasis is placed on the size and surface functionality of these systems as they are regarded as the main protagonists in dictating the particle behavior in vitro and in vivo. Current methods of manufacturing polymeric drug carriers offer a wide range of achievable particle sizes, however, they are unlikely to accurately control the size while maintaining the same production method and particle uniformity, as well as final production yield. Microfluidics technology has emerged as an efficient tool to manufacture particles in a highly controllable manner. Here, we report on tuning the size of PLGA particles at diameters ranging from sub-micron to microns using a single microfluidics device, and demonstrate how particle size influences the release characteristics, cellular uptake and in vivo clearance of these particles. Highly controlled production of PLGA particles with ~100 nm, ~200 nm and >1000 nm diameter is achieved through modification of flow and formulation parameters. Efficiency of particle uptake by dendritic cells and myeloid-derived suppressor cells isolated from mice is strongly correlated with particle size and is most efficient for ~100 nm particles. Particles systemically administered to mice mainly accumulate in liver and ~100 nm particles are cleared slower. Our study shows the direct relation between the particle size varied through microfluidics and the pharmacokinetics behavior of particles, which provides a further step towards the establishment of a customizable production process to generate tailor-made nanomedicines.

Industrial hemp (Cannabis sativa L.) is an attractive candidate for sustainable pest management due to its abundance of bioactive compounds with potential pesticidal properties. Solvent choice has a significant impact on the extraction efficiency of bioactive compounds. Deep Eutectic Solvents (DESs) are gaining popularity in extraction because they are safe and environmentally friendly, making them viable alternatives to organic solvents (OSs). This research first compared the extraction efficiency of OSs on the extraction of phytochemicals from the infloresences of two hemp varieties, Citrus and Cherry Dwarf. Inflorescences were extracted using three OSs, ethanol, ethyl acetate, and hexane. The highest level of cannabidiol (CBD; 0.69%) was extracted from Cherry Dwarf using ethanol while the level of delta-9 tetrahydrocannabinol THC (0.19%) was essentially the same in both. Therefore, Cherry Dwarf was selected to compare the extraction efficiency of DESs to the OSs. The DESs were choline chloride/ethylene glycol, citric acid/ethylene glycol, menthol/lauric acid, choline chloride/urea and choline chloride/glycerol. In the targeted analysis, choline chloride/ethylene glycol extracted the highest amount of CBD (0.87%) followed by choline chloride/urea (0.78%). As some DESs outperformed ethanol, the popular solvent for extracting cannabinoids, DESs are viable candidates to replace organic solvents.

A pattern of NK cell heterogeneity in each individual determines proliferative and functional responses of NK cells to activating stimuli. Obtaining the progeny of a single cell by cloning original population is one of the ways to study the NK cell heterogeneity. In this work, we used single cell sorting into a plate and stimulation by IL-2 and gene-modified K562 feeder cells expressing membrane-bound IL-21 (K562-mbIL21) that led to generation of phenotypically confirmed and functionally active NK cell clones. We applied two models of clone cultivation, which differently affected their phenotype, lifespan and functional activity. The first model, which included weekly restimulation of clones with K562-mbIL21 and IL-2, resulted in the generation of relatively short-lived (5-7 weeks) clones of highly activated NK cells. HLA-DR expression in the expanded NK cells correlated strongly with IFN-γ production. The second model, in which NK cells were restimulated mainly with IL-2 alone, produced long-lived clones (8-14 weeks) that expanded up to 10⁷ cells with lower ability to produce IFN-γ. Our method is applicable for studying variability in phenotype, proliferative and functional activity of the certain NK cell progeny in response to the stimulation, which may help in selecting NK cells best suited for clinical use.

Background: Patients with Inflammatory Bowel Disease (IBD) believe that diet is a key factor in the pathogenesis of their disease and in worsening their symptoms; they often follow restrictive diets that can lead to malnutrition, anxiety, and stress. Recent studies have found an association between eating disorders and IBD, particularly anorexia nervosa and ARFID (Avoidant Restrictive Food Intake Disorder). None of these studies report the association with orthorexia nervosa, that is the obsession with healthy and natural foods. Aim: to assess the risk of orthorexia nervosa in patients with IBD. Methods: 158 consecutive subjects were recruited, including 113 patients diagnosed with IBD and 45 controls. The Donini standardized questionnaire ORTO-15 was administered to assess the risk of orthorexia; clinical and demographic data were also collected. Results: patients with IBD have a prevalence of orthorexia of 77%, significantly higher than the 47% observed in the control group. In patients with IBD, the risk of orthorexia is associated with lower BMI and history of previous surgery. Conclusion: Many patients with IBD develop orthorexia nervosa that impacts the patient's psychological and social sphere, exposes them to a high risk of nutritional deficiencies, and affects quality of life. Further high quality studies are warranted to evaluate the clinical impact of orthorexia and its correlation with clinical features and frank eating disorders.

We sought to compare native T1 mapping to conventional Late gadolinium enhancement (LGE) and T2-STIR techniques in a cohort of consecutive patients undergoing cardiac MRI (CMR).. CMR was performed in 323 patients, 206 males (64%), mean age 54±8 years and in 27 age- and sex- matched healthy controls. At T2-STIR images myocardial hyperintensity suggesting edema was found in 41 patients (27%). LGE images were positive in 206 patients (64%). T1 mapping was abnormal in 171 (49%). In 206 patients (64%) a matching between LGE and native T1 was found. T1 was abnormal in 32 out of 41 (78%) with edema at T2-STIR. Overall, LGE and/or T2-STIR were abnormal in 209 patients, whereas native T1 in 154(52%). Conventional techniques and T1 mapping were concordant in 208 patients (64%). In 39 patients T1 mapping was positive despite negative conventional techniques (12%). T1 mapping was able in conditions with diffuse myocardial damage as cardiac amyloidosis, scleroderma and Fabry disease (additive role in 42%). On contrast, T1 mapping was less effective in cardiac disease with regional distribution of myocardial damage as myocardial infarction, HCM, myocarditis. In conclusion, conventional LGE/T2-STIR and T1 mapping are complementary techniques and should be used together in every CMR examination.

In the area of dental healthcare services, where patients and professionals deal with multiple auditory stimuli, this cross-sectional study reports on the intricate dynamics of sound preferences, noise obstacles, and the profound impact of music on anxiety reduction within dental office set-tings. The sample comprises of 134 dental patients, primarily females (56.7%), with varying age groups, education levels, and therapy durations in the university clinics of the department of Dentistry, National and Kapodistrian University of Athens and four private dental offices at the metropolitan area of Athens, Greece. Notably, 92.5% of the participants report no hearing loss, and 56.7% exhibit some level of noise sensitivity. The study reveals a moderate to good perceived health status (M=3.84, SD=0.95) among participants, with low perceived noise disturbance in university dental clinics. Preferences for instrumental music, foreign pop, and classical music are prominent during waiting times. Potential irritations include impersonal treatment (44%) and staff behavior (41.8%). Music player usage within the settings of the dental clinic involves radios (49.3%) and headphones (41.0%). Correlations and predictors indicate associations between health status, music preferences, and noise disturbances. More specifically, visiting the university dental clinics (β = .300, p = .005) as well as younger age (β = .300, p = .034) were significant predictors of better perceived health status. Clearer perception of external sounds while using the music player (β = .190, p = .039) was a significant predictor of better perceived health status, while poorer health was predicted by the preference of Greek folk songs (β = -.200, p = .030). Also, the use of smartphones for playing music was related to poorer health (β = -.370, p < .001). Following, younger age (β = -.270, p = .015), lower education (β = -.210, p = .035), higher noise sensitivity (β = .190, p = .027), as well as feelings of anxiety and nervousness due to ambient noise from people and machines (β = .510, p = .027) were significant predictors of noise disturbance from machines. Also, visiting private clinics (β = .240, p = .018), preferences of specific playlist (β = .310, p = .012), no music (β = .280, p = .016) and use of smartphones to play music (β = .230, p = .029) were significant predictors of noise disturbance from patients or staff. Finally, the preference of listening to a specific playlist was related to better health status (r = .190, p < .05). Findings aim to optimize eco-soundscapes in dental offices, con-tributing to enhanced patient well-being. The research underscores the potential of music inter-ventions to alleviate dental anxiety and improve the overall dental experience and quality care.

Methylation of cytosines at CpG sites in DNA, carried out by de novo by DNA methyltransferase Dnmt3a, is a basic epigenetic modification involved in gene regulation and genome stability. Aberrant CpG methylation in gene promoters leads to oncogenesis. In oncogene promoters, CpG sites often colocalize with guanine-rich sequences capable of folding into G-quadruplexes (G4s). Our in vitro study aimed to investigate how parallel G4s formed by a sequence derived from the c-MYC oncogene promoter region affect the activity of the Dnmt3a catalytic domain (Dnmt3a-CD). For this purpose, we designed synthetic oligonucleotide constructs: c-MYC G4-forming oligonucleotide and linear double-stranded DNA containing an embedded stable extrahelical c-MYC G4. The topology and thermal stability of G4 structures in these DNA models were analyzed by physicochemical techniques. We showed that Dnmt3a-CD specifically binds to an oligonucleotide containing c-MYC G4, resulting in inhibition of its methylation activity. c-MYC G4 formation in a double-stranded context significantly reduce Dnmt3a-CD-induced methylation of a CpG site located in close proximity to the quadruplex structure; this effect depends on the distance between the non-canonical structure and the specific CpG site. One would expect DNA hypomethylation near the G4 structure, while regions distant from this non-canonical form would maintain a regular pattern of high methylation levels. We hypothesize that the G4 structure sequesters the Dnmt3a-CD and impedes its proper binding to B-DNA, resulting in hypomethylation and activation of c-MYC transcription.

The present paper reports an exact approach quantifying the electromagnetic contribution to the anomalous magnetic moment occurring in isolated system comprised of non-composite particle carrying elementary electric charge. Essential averaging procedure and regularization of the electromagnetic field potentials necessary when quantifying the electromagnetic self-interactions and when deriving equations of motion without singularities and obeying the conservation laws are thoroughly discussed. The study shows that the dynamics of the considered system is associated to unique classical transcendental equations of motion satisfied by the particle's velocity and the electromagnetic contribution to the anomalous $g$-factor known from the quantum electrodynamics. The equations of motion lead to an exact analytical expression for the anomalous $g$-factor that provides more accurate result than that calculated with the aid of quantum electrodynamics. It matches the experimentally measured value reported in the literature to a one part per trillion. We obtain a_e=0.00115965218000(65) thus reveling the potential of non-perturbative, non-probability methods in predicting the electron's anomalous g-factor.

G-quadruplex, a unique secondary structure in nucleic acids found throughout human genome elicited widespread interest in the field of therapeutic research. Being present in key regulatory regions of oncogenes, G-quadruplex structure regulates transcription, translation, splicing, telomere stability etc. Changes in its structure and stability lead to differential expression of oncogenes causing cancer. Thus, targeting G-Quadruplex structures with small molecules/ other biologics has shown elevated research interest. Covering previous reports, in this review we try to enlighten the facts on the structural diversity in G-quadruplex ligands aiming to provide newer insights to design first-in-class drugs for the next generation cancer treatment.

The concept of vulnerable carotid plaques is pivotal in understanding the pathophysiology of is-chemic stroke secondary to large-artery atherosclerosis. At the macroscopic evaluation, vulnera-ble plaques are characterized by one or more of the following features: microcalcification, neo-vascularization, lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), thin fibrous caps, plaque surface ulceration, huge dimension determining stenosis, and plaque rupture. Recognizing these macroscopic characteristics is crucial to estimating the risk of cerebrovascular events, also in case of non-significant (less than 50%) stenosis. Inflammatory biomarkers, such as cytokines and adhesion molecules, lipid-related markers like oxidized low-density lipoprotein (LDL), and proteolytic enzymes capable of degrading extracellular matrix components are among the key molecules that will be scrutinized for their associative roles in plaque instability. Through their quantification and evaluation, these biomarkers reveal intricate molecular cross-talking govern-ing plaque inflammation, rupture potential, and thrombogenicity. Current evidence demonstrates that plaque vulnerability phenotypes are multiple and heterogeneous and are associated with as many highly complex molecular pathways that determine the activation of an immune-mediated cascade that culminates in thromboinflammation. This narrative review provides a comprehen-sive analysis of current knowledge on molecular biomarkers expressed by symptomatic carotid plaques. It explores the association of these biomarkers with the structural and compositional at-tributes that characterize vulnerable plaques

Background: Mental capacity is a fundamental aspect that enables patients to fully par-ticipate in various healthcare procedures. To assist healthcare professionals (HCPs) in assessing patients' capacity, especially in the mental health field, several standardized tools have been developed. These tools include the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), and the Competence Assessment Tool for Psychiatric Advance Directives (CAT-PAD). The core dimensions explored by these tools include Understanding, Appreciation, Reasoning, and Expression of a choice. Objective: This meta-analysis aimed to investigate potential differences in deci-sion-making capacity within the healthcare context among groups of patients with bi-polar disorder (BD) and schizophrenia spectrum disorder (SSD). Methods: A systematic search was conducted on Medline/Pubmed, and Scopus. Addi-tionally, Google Scholar was manually inspected, and a manual search of emerging re-views and reference lists of the retrieved papers was performed. Eligible studies were specifically cross-sectional, utilizing standardized assessment tools, and involving pa-tients diagnosed with BD and SSD. Data from the studies were independently extracted and pooled using random-effect models. Hedges g was used as a measure for outcomes. Results: Six studies were identified, with three studies using the MacCAT-CR, two studies the MacCAT-T, and one the CAT-PAD. The participants included 189 individuals with BD and 324 individuals with SSD. The meta-analysis revealed that patients with BD performed slightly better, and the difference was statistically significant, compared to patients with SSD, particularly in the domain of Appreciation (ES=0.23, 95% CI: 0.01 to 0.04, p=0.037). There was no statistically significant difference between the two groups for Understanding (ES=0.09, 95% CI: - 0.10 to 0.27, p=0.352), Reasoning (ES=0.18, 95% CI: - 0.12 to 0.47, p=0.074), and Expression of a choice (ES = 0.23, 95% CI: - 0.01 to 0.48, p=0.60). In the sensitivity analysis, furthermore, when considering only studies involving patients in symptomatic remission, the difference for Appreciation also resulted in non-significant (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). Conclusions: These findings indicate that there are no significant differences between patients with BD and SSD during remission phases, while differences are minimal during acute phases. The usefulness of standardized assessment of capacity at any stage of the illness should be considered, both for diagnostic-therapeutic phases and for research and advance directives. Further studies are necessary to understand the reasons for the overlap in capacity between the two diagnostic categories compared in this study.

The aim of this article is to review hydrogen combustion applications within the energy transition framework. Hydrogen blends are also included, from the well known hydrogen enriched natural gas (HENG) to the hydrogen and ammonia blends whose chemical kinetics is still not clearly defined. Hydrogen and hydrogen blends combustion characteristics will be firstly summarized, in terms of standard properties like the laminar flame speed and the adiabatic flame temperature, but also evidencing the critical role of hydrogen preferential diffusion in burning rate enhancement and the drastic reduction in radiative emission with respect to natural gas flames. Then, combustion applications in both thermo-electric power generation (based on internal combustion engines, i.e., gas turbines and piston engines) and hard-to-abate industry (requiring high temperature kilns and furnaces) sectors will be considered, highlighting the main issues due to hydrogen addition related to safety, pollutant emissions, and potentially negative effects on industrial products (e.g., glass, cement and ceramic).

It was for long time believed that lidar systems based on the use of high-repetition micro-pulse lasers could be effectively used to only stimulate atmospheric elastic backscatter echoes, and thus only exploited in elastic backscatter lidar systems. Their application to stimulate rotational and roto-vibrational Raman echoes, and consequently their exploitation in atmospheric thermodynamic profiling, was considered not feasible based on the technical specifications possessed by these laser sources until a few years ago. However, recent technological advances in the design and development of micro-pulse lasers, presently achieving high UV average powers (1-5 W) and small divergences (0.3-0.5 mrad), in combination with the use of large aperture telescopes (0.3-0.4 m diameter primary mirrors), allow to presently develop micro-pulse laser-based Raman lidars capable to measure the vertical profiles of atmospheric thermodynamic parameters, namely water vapour and temperature, both in daytime and nighttime. This paper is aimed at demonstrating the feasibility of these measurements and at illustrating and discussing the high achievable performance level, with a specific focus on water vapour profile measurements. The technical solutions identified in the design of the lidar system and their technological implementation within the experimental setup of the lidar prototype are also carefully illustrated and discussed.

Conventional monitoring relies on "in vivo" (non-destructive) measurements of aboveground organ traits (such as stems, branches, and leaves) to analyze plantation growth trends and assess the effectiveness of management practices like watering and fertilization. This study reveals the necessity of “ex vivo” (destructive) approaches, post-excavation, to ensure fully reliable monitoring of plantation performance, including belowground organ growth and development trends. We showcase the effectiveness of dendrometric analysis, which measures the annual ring width in the secondary xylem (wood) of the taproot and stem. Monitoring above- and belowground organ growth trends allow for the exploration of similarities and differences in how different tree organs respond to internal and external factors. Such monitoring is especially crucial for assessing plantation performance in challenging climates, such as those found in arid and semi-arid lands.

Our work is regarding the analysis of land use changes, in the light of “saving soil” against the expansion due to unearned plus value of land: The loss of natural and agricultural surface in front of the expanding urban environment is a critical aspect of unsustainability of urban development, especially in the way it was carried out in the past decades. The measure of the physical transition of land use and characters from a more natural condition of land surface to a new artificial one, joint with a parallel analysis of the increase of land value due to such change is nowadays a major land-policy tool. The interplay of urban economics regulation with planning, reveals new key issues in urban governance and environmental preservation. In this paper it will be shown some experiment about the impact assessment of soil take, related with the seek of valorization of property inside the planning process. Our paper reports as well about the experimental activity carried out inside the MITO Lab of the Polytechnic of Bari, where reports about property values and environmental values have been produced, specially looking at the reality of the Apulia, a southern Italian Region, that is rich of farmlands and coastlines, often invaded by constructions with a severe loss of nature, landscape and ecosystems services.

Potentially, such an approach would significantly increase the effectiveness of therapy for a number of infectious and other diseases, reduce the dosage of antibiotics, shorten the duration of treatment, and reduce the risk of developing resistance. Moreover, the use of a polymer carrier with covalently bound organic molecules of different structures avoids problems with different (suboptimal) solubility and bio-distribution, which would be almost inevitable when using the same compounds separately. It would be very difficult to find antibiotic/adjuvant pairs that simultaneously achieve optimal concentrations in the same target cells. In our case, terpenoids and alkylbenzenes used as adjuvants are practically insoluble as individual compounds and their unacceptable pharmacological properties would not allow them to be used as efflux pump inhibitors.

Background and Aims: Dyslipidemia and cardiovascular diseases (CAD) are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from steatosis to hepatocellular carcinoma (HCC). The rs599839 A>G variant, in the CELSR2-PSRC1-SORT1 cluster, has been associated CAD, but its impact on metabolic traits and liver damage in NAFLD has not been investigated yet. Methods: We evaluated the effect of the rs599839 variant in 1426 NAFLD patients (Overall cohort) of whom 131 have HCC (NAFLD-HCC), in 500,000 individuals from the UK Biobank Cohort (UKBBC) and in 366 HCC samples from The Cancer Genome Atlas (TCGA). Hepatic PSRC1, SORT1 and CELSR2 expressions were evaluated by RNAseq (n=125). Results: The rs599839 variant was associated with reduced circulating LDL, carotid intima-media thickness, carotid plaques and hypertension (p<0.05) in NAFLD patients and with protection against dyslipidemia in UKBBC. The G allele was associated with higher risk of HCC and advanced tumor stage (p<0.05) in the Overall cohort. Hepatic PSRC1, SORT1 and CELSR2 expressions were increased in NAFLD patients carrying the rs599839 variant (p<0.0001). SORT1 mRNA levels negatively correlated with circulating lipids and with those of genes involved in lipoprotein turnover (p<0.0001). Conversely, PSRC1 expression was positively related to that of genes implicated in cell proliferation (p<0.0001). In TCGA, PSRC1 over-expression promoted more aggressive HCC development (p<0.05). Conclusions: In sum, the rs599839 A>G variant improves dyslipidemia thus protecting against CAD in NAFLD patients, but as one it might promote HCC development by modulating SORT1 and PSRC1 expressions which impact on lipid metabolism and cell proliferation, respectively

In this article/review, the selective interactions of several berberine and palmatine derivatives with various DNA G-quadruplex structures are reported. These derivatives were constructed starting from two natural compounds, berberine and palamatine, through specific synthetic passages following two different schemes for each of them and using several substituents. The details of these synthesis are also described. Indeed, the study of the interactions of these derivative compounds with various G-quadruplex forming sequences was carried out by means of various structural and biochemical techniques. The results show that the presence of suitable side chains are very useful to improve the interaction of the ligands with G-quadruplex structures. Thus, since G-quadruplex formation is promoted by these compounds, which have never been reported before, these may be tested as potential anticancer drugs.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) has proven to be effective in reducing the rate of recurrence and disease as secondary prevention (evidence-based intervention) in patients who have suffered from myocardial infarction (MI). CR is a multidisciplinary path in which the patient is followed pharmacologically, from a psychological, nutritional, nursing and physiotherapy point of view. Post-MI patients present a reduction in the performance of the diaphragm muscle, the main inspiratory muscle, and this condition can become a risk factor for further relapses or for the onset of heart failure. Despite the solidity of the international guidelines for CR, the latter are lacking in specifically indicating an evaluation and training path regarding the inspiratory muscles in post-MI patients who have not undergone cardiac surgery. The article reviews the information on the adaptation of the diaphragm post-MI and highlights the need for clearer indications for a rehabilitation process that gives importance to the diaphragm.

Reducing GHG emissions is a crucial challenge in urban areas, characterized by high energy consumption and reduced exposure to nature. In this context, the urban green system could play a pivotal role. In the literature, scholars analyzed both the ability of species-specific and layout-specific green infrastructures to increase carbon sequestration and the best location sites of new green infrastructures, to increase the provision of overall ecosystem services. There is a lack of studies helping green urban planners and designers choose where and which green infrastructure to implement, based on vegetation species-specific performance and local carbon emissions of city components. This paper uses tree inventory data from a medium-sized city in central Italy (Perugia) to develop a spatial analysis of the urban parks' performance in carbon sequestration. Then, the method evaluates the carbon emission of a public city building to generate a spatialized balance between buildings’ demand and trees’ supply, to support local decisions about the best locations for new green infrastructures and the choice between species. The paper contributes to GIS-based tools that vary the recommended location sites and species for new green infrastructures based on the demanded ecosystem service.

Food production is a complex matter, affecting people’s lives, organizations’ profits, and the well-being of the whole planet and has multifaceted ethical considerations surrounding its production, distribution, and consumption. This paper addresses the pressing need to confront ethical challenges within the food system, encompassing issues such as environmental sustainability, food security, and individual food choices for better oral and systemic health of all individuals around the globe. From agricultural practices to global trade and food waste, ethical implications are addressed across various domains, highlighting the interconnectedness of ethical decision-making in the food industry. Central themes explored include the ethical dimensions of food production methods, the impact of global trade on food ethics, and the role of individuals in making ethically informed food choices. Additionally, the paper dives into the spiritual and physical significance of food, particularly through the lens of oral health as a gateway to holistic well-being. Recognizing the complexity of the food ecosystem, the paper calls for serious interventions in legislation and economics to promote ethical protocols and techniques for sustainability reasons. It emphasizes the importance of ethical considerations in food safety management systems, regulatory frameworks, and quality standards. Moreover, the paper underscores the need for a comprehensive approach to address ethical dilemmas and moral values inherent in the food industry and oral health policies, advocating for the adoption of the precautionary principle and ethical decision-making frameworks. The article aims to serve as a call to action for stakeholders across the food industry and the healthcare sector, to prioritize ethical practices, promote transparency, rearrange economic parameters and work towards a more sustainable and equitable food system for inner and outer oral and systemic health and human sustainability for all.

In the bioprinting process, controlling the motion of bioprinters involves a computer-aided design (CAD) model, converting that model into g-code, and transmitting the motion commands to the bioprinters. The g-code file contains information about the motion of the axes and can be generated using various software. However, a challenge arises when using g-code between different bioprinters. Therefore, the objective of this study was to propose a reliable method for analyzing the differences in 3D bioprinting devices by parameterizing a crucial variable for extrusion bioprinting: the E-value. Four bioprinters from three different manufacturers were used to investigate the extrusion behavior when subjected to the same E-value.

Post-translational modifications (PTMs) of histone residues shape the landscape of gene expression by modulating the dynamic process of RNAPII transcription. The contribution of particular histone modifications to the definition of distinct RNAPII transcription stages remains poorly characterized in plants. Chromatin Immuno-precipitation combined with next-generation sequencing (ChIP-seq) resolves the genomic distribution of histone modifications. Here, we review histone PTM ChIP-seq data in Arabidopsis thaliana and find support for a Genomic Positioning System (GPS) that guides RNAPII transcription. We review the roles of histone PTM “readers”, “writers” and “erasers”, with a focus on the regulation of gene expression and biological functions in plants. The distinct functions of RNAPII transcription during the plant transcription cycle may in part rely on the characteristic histone PTMs profiles that distinguish transcription stages.

This review summarizes the most recent developments of research on protozoan parasite infections ac-quired through food and drinking water and is aimed at gathering updated knowledge on the risk factors, illnesses caused, and measures for prevention. Reports included dated from 2019 to the present and regarded recent outbreaks and cases of severe infec-tions, prevalence in different population segments and food handlers, and occurrence in food and drinking water. Cryptosporidium spp., Entamoeba histolytica, Giardia intestinalis, Trypanosoma cruzi and Toxoplasma gondii were the microorganisms most frequently involved in large outbreaks and/or severe infections, while Cyclospora cayetanensis was most frequently involved in single case reports. Cystoisospora belli was implied in severe infections in immunocompromised patients, while Blastocystis homi-nis, Sarcocystis spp., Dientamoeba fragilis, Endolimax nana and Pentatrichomonas hominis appeared to be less relevant for number of symptomatic infections and pathogenic potential. A progressive improvement in surveillance of protozoan infections and infection sources was highlighted, especially in developed countries. The apparent increase in cases was concomitant with the implementa-tion of reporting systems and the application of molecular diagnostic methods that represent valuable in-struments for establishing epidemiological links and preventing or limiting outbreaks. The pathogenic role and sources of infection should be better elucidated for some species.

Air pollution poses a significant risk to public health and ecosystems. The use of sophisticated models to simulate the transformation and dispersion of pollutants in the atmosphere is a recognized method to assess air pollution levels and its sources and inform policy decisions for effective mitigation strategies in urban and industrial environments. The reliability of models depends, in part, on the sensitivity to the variance of input parameters, which can introduce uncertainty into the model's predictions. This uncertainty is especially challenging when the input parameters exhibit inherent variability. In this study, we analyse the uncertainty of an integrated emission/dispersion model by evaluating the relationship between input parameters and model outcomes. We uncover new aspects of this relationship while clarifying some previously known dependencies. Wind speed was found to have the most significant effect on calculated concentrations, with small differences leading to substantial concentration variations. The time of day, which reflects prevailing vertical turbulence conditions, was also found to have a notable impact on concentrations, whereas ambient temperature can also significantly influence model’s results. Based on these findings, we offer specific recommendations for regulators and scientists involved in environmental impact assessment to improve the accuracy and reliability of air pollution modelling.

Background: Several kinds of research say that adjuvant blood glucose and blood pressure are usual, but an efficient solution for medical application count remains. This review analyzes the pandemic blood pressure and blood glucose to identify the publications which tell about the clinical practices and research gaps in systematic research.Methods: A study guides to identify the research of Blood Pressure (BP) and Blood Glucose. In order to analyze the recent innovations and research on BP and Blood glucose, the relevant publications and literature from journals were identified.Results: Co-morbidity of BP and Blood glucose is reported as very high. The commonness of blood pressure is thrice as high in type I diabetes patients and almost two times higher in type II diabetes patients when compared to others without Diabetes. The pervasiveness of getting depression is more in the female when compared with men. A detailed study about the linkage of BP and blood glucose tells that the relationship between them is not exactly clear.Limitations: Nearly all reviews providing the linkage of BP and blood glucose are with some limitations and they are not providing any clear conclusion.Conclusions: Present research tells that people having high blood glucose will have a greater chance of getting high blood pressure. More research is needed to state the linkage between BP, blood glucose, and the growth of diabetes mellitus issues and to provide support for managing Diabetes.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

The direct radiative effects of atmospheric aerosols are essential for climate, as well as for other societal areas, like the energy sector. The goal of the present study is to exploit the newly devel-oped ModIs Dust AeroSol (MIDAS) dataset for quantifying the direct effects on the downwelling surface solar irradiance (DSSI), induced by the total and dust aerosols amount, under clear-sky conditions and the associated impacts on solar energy for the broader Mediterranean basin, over the period 2003 – 2017. Aerosol optical depth (AOD) and dust optical depth (DOD) derived by the MIDAS dataset, along with additional aerosol and dust optical properties and atmospheric variables were used as inputs to radiative transfer modeling to simulate DSSI components. A 15-year climatology of AOD, DOD and of clear-sky Global Horizontal Irradiation (GHI) and Direct Normal Irradiation (DNI) was derived. The spatial and temporal variability of the aerosol and dust effects on the different DSSI components was assessed. Aerosol attenuation of annual GHI and DNI range from 1-13% and 5-47%, respectively. Significant attenuation by dust 2-10% and 9-37% was found over North Africa and the Middle East, contributing to 45-90% of the total aero-sol effects. The mean GHI and DNI attenuation during extreme dust episodes reached values up to 12% and 44%, respectively, for different areas. After 2008 a decline of aerosol effects on DSSI was found, attributed mainly to the dust component. Sensitivity analysis using different AOD/DOD inputs from Copernicus Atmosphere Monitoring Service (CAMS) reanalysis dataset, revealed CAMS underestimation of aerosol and dust radiative effects compared to MIDAS, due to slight AOD and stronger DOD underestimation, respectively.

Although Eulerian approaches are standard in computational acoustics, they are less effective for certain classes of problems like bubble acoustics and combustion noise. A different approach for solving acoustic problems is to compute with individual particles following particle motion. In this paper, a Lagrangian approach to model sound propagation in moving fluid is presented and implemented numerically, using three meshfree methods to solve the Lagrangian acoustic perturbation equations (LAPE) in the time domain. The LAPE split the fluid dynamic equations into a set of hydrodynamic equations for the motion of fluid particles and perturbation equations for the acoustic quantities corresponding to each fluid particle. Then, three meshfree methods, the smoothed particle hydrodynamics (SPH) method, the corrective smoothed particle (CSP) method, and the generalized finite difference (GFD) method, are introduced to solve the LAPE and the linearized LAPE (LLAPE). The SPH and CSP methods are widely used meshfree methods, while the GFD method based on the Taylor series expansion can be easily extended to higher orders. Applications to modeling sound propagation in steady or unsteady fluids in motion are outlined, treating a number of different cases in one and two space dimensions. A comparison of the LAPE and the LLAPE using the three meshfree methods is also presented. The Lagrangian approach shows good agreement with exact solutions. The comparison indicates that the CSP and GFD method exhibit convergence in cases with different background flow. The GFD method is more accurate, while the CSP method can handle higher Courant numbers.

We used an ultrasensitive, broadband optomechanical ultrasound sensor to study the acoustic signals produced by pressurized nitrogen escaping from a variety of small syringes. Harmonically related jet tones extending into the MHz region were observed for a certain range of flow (i.e., Reynolds number), in qualitative agreement with historical studies on gas jets emitted from pipes/orifices of much larger dimensions. For higher turbulent flow rates, we observed broadband ultrasonic emission in the ~ 0 – 5 MHz range, likely limited on the upper end by attenuation in air. These observations are made possible by the broadband, ultrasensitive response (for air-coupled ultrasound) of our optomechanical devices. Aside from their theoretical interest, our results could have practical implications for the non-contact monitoring and detection of early-stage leaks in pressured fluid systems.