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Cardiovascular diseases represent a major issue in terms of morbidity and mortality for dialysis patients. This morbidity is due to the accelerated atherosclerosis observed in these patients. Atherosclerosis is a chronic inflammatory disease characterized by key players such as monocytes, macrophages, or oxidized LDLs. Monocytes-macrophages are classified into subsets of polarized cells, with M1 and M2 macrophages considered, respectively, as pro- and anti-inflammatory. (1) Methods: The monocyte subsets and phenotypes were analyzed by flow cytometry. These data were completed by the quantification of plasma M-CSF, IL-8, CRP, Mox-LDLs, Apo-B, Apo-AI, chloro-tyrosine, and homocitrulline concentrations. The statistical differences and associations between two continuous variables were assessed using the Mann&ndash, Whitney U test and Spearman&rsquo, s correlation coefficient, respectively. (2) Results: Hemodialyzed patients showed a significant increase in their concentrations of CRP, M-CSF, and IL-8 (inflammation biomarkers), as well as chloro-tyrosine and homocitrulline (myeloperoxidase-associated oxidative stress biomarkers). Moreover, we observed a higher percentage of M2 monocytes in the plasma of hemodialysis patients as compared to the controls. (3) Conclusions: Our data suggest that oxidative stress and an inflammatory environment, which is amplified in hemodialysis patients, seems to favor an increase in the concentration of circulating M-CSF, therefore leading to an increase in M2 polarization among circulating monocytes.

Circulating calprotectin is a potential biomarker for endovascular inflammation in type 2 diabetes mellitus (T2DM). We investigated the determinants of calprotectin and its relationship with the presence of cardiovascular disease (CVD) in 362 T2DM patients included in the Diabetes and Lifestyle Cohort Twente-1 (DIALECT-1) study. Lifestyle exposures, including nutrition, were determined by validated questionnaires. CVD was defined as coronary artery diseases, strokes, and peripheral artery diseases. Median serum calprotectin levels were 1.04 mg/L [IQR: 0.73&ndash, 1.46 mg/L] and were higher in women (1.11 mg/L) than men (0.96 mg/L, p = 0.007). Current smoking was a major independent determinant of circulating calprotectin, with a 51% higher calprotectin compared to never smoking (p &lt, 0.001). Albuminuria (p = 0.011), former smoking (p = 0.023), and intake of mono- and disaccharides (p = 0.005) also contributed independently to circulating calprotectin. Each incremental increase in calprotectin level was associated with 1.36-times higher odds for CVD (95% CI 1.04&ndash, 1.77, p = 0.026). In the current study, calprotectin was the only inflammatory parameter significantly associated with CVD. The strong association of circulating calprotectin with smoking, a well-known direct cause of vascular inflammation, and also with CVD, stresses the urge for further research to define its role as a biomarker in T2DM.

Tacrolimus has been used to induce remission in patients with steroid-refractory ulcerative colitis. It poses a problem of large individual differences in dosage necessary to attain target blood concentration and, often, this leads to drug inefficacy. We examined the difference in mRNA expression levels of ATP binding cassette transporter B1 (ABCB1) between inflamed and non-inflamed tissues, and the influence of CYP3A5 genotype on tacrolimus therapy. The mRNA expression of CYP3A4 in colonic mucosa and that of cytochrome p450 3A5 (CYP3A5) and ABCB1 in inflamed and non-inflamed areas were examined in 14 subjects. The mRNA expression levels of CYP3A5 were higher than that of CYP3A4. The mRNA expression of ABCB1 was lower in the inflamed than in the non-inflamed mucosa, despite that of CYP3A5 mRNA level being not significantly changed. Hence, the deterioration of the disease is related to the reduction of the barrier in the inflamed mucosa. The relationship between CYP3A5 genotype and blood concentration, dose, and concentration/dose (C/D) ratio of tacrolimus in 15 subjects was studied. The tacrolimus dose to maintain equivalent blood concentrations was lower in CYP3A5*3/*3 than in CYP3A5*1 carriers, and the C/D ratio was significantly higher in the latter. Thus, CYP3A5 polymorphism information played a role in determining the initial dose of tacrolimus. Furthermore, since the effect of tacrolimus appears earlier in CYP3A5*3/*3 than in CYP3A5*1/*1 and *1/*3, it seems necessary to change the evaluation time of therapeutic effect by CYP3A5 genotype. Additionally, the relationship between CYP3A5 genotype and C/D ratio of tacrolimus in colonic mucosa was investigated in 10 subjects. Tacrolimus concentration in the mucosa was two-fold higher in CYP3A5*3/*3 than in CYP3A5*1 carriers, although no significant difference in tacrolimus-blood levels was observed. Therefore, the local concentration of tacrolimus affected by CYP3A5 polymorphism might be related to its therapeutic effect.

Caribbean Christmas tree worms (Annelida: Polychaeta: Serpulidae: Spirobranchus) are considered host generalists in their associations with anthozoan (Scleractinia) and hydrozoan (Millepora) stony corals [...]

Tick-borne encephalitis (TBE) is associated with a range of disease severity. The reasons for this heterogeneity are not clear. Levels of serum IgG antibodies to TBE virus (TBEV) were determined in 691 adult patients during the meningoencephalitic phase of TBE and correlated with detailed clinical and laboratory parameters during acute illness and with the presence of post-encephalitic syndrome (PES) 2–7 years after TBE. Specific IgG antibody levels ranged from below cut-off value (in 32/691 patients, 4.6%), to 896 U/mL (median = 37.3 U/mL). Patients with meningoencephalomyelitis were more often seronegative (24.3%, 9/37) than those with meningoencephalitis (4.7%, 20/428) or meningitis (1.3%, 3/226). Moreover, patients with antibody levels below cut-off had longer hospitalization (13 versus 8 days), more often required intensive care unit treatment (22% versus 8%) and artificial ventilation (71% versus 21%), and had a higher fatality rate (3/32, 9.4% versus 1/659, 0.2%) than seropositive patients. These results were confirmed when antibody levels, rather than cut-off values, were correlated with clinical parameters including the likelihood to develop PES. Low serum IgG antibody responses against TBEV at the onset of neurologic involvement are associated with a more difficult clinical course and unfavorable long-term outcome of TBE, providing a diagnostic and clinical challenge for physicians.

The two most important bacterial phyla in the gastrointestinal tract, Firmicutes and Bacteroidetes, have gained much attention in recent years. The Firmicutes/Bacteroidetes (F/B) ratio is widely accepted to have an important influence in maintaining normal intestinal homeostasis. Increased or decreased F/B ratio is regarded as dysbiosis, whereby the former is usually observed with obesity, and the latter with inflammatory bowel disease (IBD). Probiotics as live microorganisms can confer health benefits to the host when administered in adequate amounts. There is considerable evidence of their nutritional and immunosuppressive properties including reports that elucidate the association of probiotics with the F/B ratio, obesity, and IBD. Orally administered probiotics can contribute to the restoration of dysbiotic microbiota and to the prevention of obesity or IBD. However, as the effects of different probiotics on the F/B ratio differ, selecting the appropriate species or mixture is crucial. The most commonly tested probiotics for modifying the F/B ratio and treating obesity and IBD are from the genus Lactobacillus. In this paper, we review the effects of probiotics on the F/B ratio that lead to weight loss or immunosuppression.

Quorum sensing (QS) is often required for the formation of bacterial biofilms and is a popular target of biofilm control strategies. Previous studies implicate the ComQXPA quorum sensing system of Bacillus subtilis as a promoter of biofilm formation. Here, we report that ComX signaling peptide deficient mutants form thicker and more robust pellicle biofilms that contain chains of cells. We confirm that ComX positively affects the transcriptional activity of the PepsA promoter, which controls the synthesis of the major matrix polysaccharide. In contrast, ComX negatively controls the PtapA promoter, which drives the production of TasA, a fibrous matrix protein. Overall, the biomass of the mutant biofilm lacking ComX accumulates more monosaccharide and protein content than the wild type. We conclude that this QS phenotype might be due to extended investment into growth rather than spore development. Consistent with this, the ComX deficient mutant shows a delayed activation of the pre-spore specific promoter, PspoIIQ, and a delayed, more synchronous commitment to sporulation. We conclude that ComX mediated early commitment to sporulation of the wild type slows down biofilm formation and modulates the coexistence of multiple biological states during the early stages of biofilm development.

Colorectal cancer (CRC), the third most common type of cancer, is the second leading cause of cancer-related mortality rates worldwide. Although modern research was able to shed light on the pathogenesis of CRC and provide enhanced screening strategies, the prevalence of CRC is still on the rise. Studies showed several cellular signaling pathways dysregulated in CRC, leading to the onset of malignant phenotypes. Therefore, analyzing signaling pathways involved in CRC metastasis is necessary to elucidate the underlying mechanism of CRC progression and pharmacotherapy. This review focused on target genes as well as various cellular signaling pathways including Wnt/β-catenin, p53, TGF-β/SMAD, NF-κB, Notch, VEGF, and JAKs/STAT3, which are associated with CRC progression and metastasis. Additionally, alternations in methylation patterns in relation with signaling pathways involved in regulating various cellular mechanisms such as cell cycle, transcription, apoptosis, and angiogenesis as well as invasion and metastasis were also reviewed. To date, understanding the genomic and epigenomic instability has identified candidate biomarkers that are validated for routine clinical use in CRC management. Nevertheless, better understanding of the onset and progression of CRC can aid in the development of early detection molecular markers and risk stratification methods to improve the clinical care of CRC patients.

Anticancer activity of different phenols is documented, but underlying mechanisms remain elusive. Recently, we have shown that cannabidiol kills the cells of acute lymphoblastic leukemia (ALL) by a direct interaction with mitochondria, with their consequent dysfunction. In the present study, cytotoxic effects of several phenolic compounds against human the T-ALL cell line Jurkat were tested by means of resazurin-based metabolic assay. To unravel underlying mechanisms, mitochondrial membrane potential (∆&Psi, m) and [Ca2+]m measurements were undertaken, and reactive oxygen species generation and cell death were evaluated by flow cytometry. Three out of eight tested phenolics, cannabidiol, curcumin and quercetin, which displayed a significant cytotoxic effect, also dissipated the ∆&Psi, m and induced a significant [Ca2+]m increase, whereas inefficient phenols did not. Dissipation of the ∆&Psi, m by cannabidiol was prevented by cyclosporine A and reverted by Ru360, inhibitors of the permeation transition pore and mitochondrial Ca2+ uniporter, respectively. Ru360 prevented the phenol-induced [Ca2+]m rise, but neither cyclosporine A nor Ru360 affected the curcumin- and quercetin-induced ∆&Psi, m depolarization. Ru360 impeded the curcumin- and cannabidiol-induced cell death. Thus, all three phenols exert their antileukemic activity via mitochondrial Ca2+ overload, whereas curcumin and quercetin suppress the metabolism of leukemic cells by direct mitochondrial uncoupling.

The dynamic damage of cracked rock threatens the stability of rock structures in rock engineering applications such as underground excavation, mineral exploration and rock slopes. In this study, the dynamic damage of cracked rock with different spatial geometry was investigated in an experimental method. Approximately 54 sandstone specimens with different numbers of joints and different filling materials were tested using the split Hopkinson pressure bar (SHPB) apparatus. The energy absorption in this process was analyzed, and the damage variable was obtained. The experimental results revealed that the dynamic damage of cracked rock is obviously influenced by the number of cracks; the larger the number, the higher the energy absorption and the bigger the dynamic damage variable. Moreover, it was observed from the dynamic compressive experiments that the energy absorption and the dynamic variable decreased with the strength and cohesion of the filling material, indicating that the filling material of crack has considerate influence on the dynamic damage of cracked rock.

Lithium is the prototype mood-stabilizer used for acute and long-term treatment of bipolar disorder. Cumulated translational research of lithium indicated the drug’s neuroprotective characteristics and, thereby, has raised the option of repurposing it as a drug for neurodegenerative diseases. Lithium’s neuroprotective properties rely on its modulation of homeostatic mechanisms such as inflammation, mitochondrial function, oxidative stress, autophagy, and apoptosis. This myriad of intracellular responses are, possibly, consequences of the drug’s inhibition of the enzymes inositol-monophosphatase (IMPase) and glycogen-synthase-kinase (GSK)-3. Here we review lithium’s neurobiological properties as evidenced by its neurotrophic and neuroprotective properties, as well as translational studies in cells in culture, in animal models of Alzheimer’s disease (AD) and in patients, discussing the rationale for the drug’s use in the treatment of AD.

In recent years, advances in drug therapy for head and neck squamous cell carcinoma (HNSCC) have progressed rapidly. In addition to cytotoxic anti-cancer agents such as platinum-based drug (cisplatin and carboplatin) and taxane-based drugs (docetaxel and paclitaxel), epidermal growth factor receptor-tyrosine kinase inhibitors (cetuximab) and immune checkpoint inhibitors such as anti-programmed cell death-1 (PD-1) antibodies (nivolumab and pembrolizumab) have come to be used. The importance of anti-cancer drug therapy is increasing year by year. Therefore, we summarize clinical trials of molecular targeted therapy and biomarkers in HNSCC from previous studies. Here we show the current trends and future prospects of molecular targeted therapy in HNSCC.

Flatbed scanners (FBSs) provide non-contact scanning capabilities that could be used for the on-machine verification of layer contours in additive manufacturing (AM) processes. Layer-wise contour deviation assessment could be critical for dimensional and geometrical quality improvement of AM parts, because it would allow for close-loop error compensation strategies. Nevertheless, contour characterisation feasibility faces many challenges, such as image distortion compensation or edge detection quality. The present work evaluates the influence of image processing and layer-to-background contrast characteristics upon contour reconstruction quality, under a metrological perspective. Considered factors include noise filtering, edge detection algorithms, and threshold levels, whereas the distance between the target layer and the background is used to generate different contrast scenarios. Completeness of contour reconstruction is evaluated by means of a coverage factor, whereas its accuracy is determined by comparison with a reference contour digitised in a coordinate measuring machine. Results show that a reliable contour characterisation can be achieved by means of a precise adjustment of image processing parameters under low layer-to-background contrast variability. Conversely, under anisotropic contrast conditions, the quality of contour reconstruction severely drops, and the compromise between coverage and accuracy becomes unbalanced. These findings indicate that FBS-based characterisation of AM layers will demand developing strategies that minimise the influence of anisotropy in layer-to-background contrast.

Metallic components consisting of magnesium, aluminum, steel, and their alloys are widely used in a plethora of applications because of their exceptional mechanicalproperties and their overall durability. However, they are often damaged by mechanical or chemical processes. Mechanical damage that is caused by the impact of solid particles is called erosion, while electrochemical damage that results from chemical degradation is termed corrosion. The corrosion phenomena, to which every metallic substrate is subjected, eventually result in the degradation of the metal and the deterioration of itsproperties.

Transient receptor potential ankyrin 1 (TRPA1) is a membrane-bound ion channel found in neurons, where it mediates nociception and neurogenic inflammation. Recently, we have discovered that TRPA1 is also expressed in human osteoarthritic (OA) chondrocytes and downregulated by the anti-inflammatory drugs aurothiomalate and dexamethasone. We have also shown TRPA1 to mediate inflammation, pain, and cartilage degeneration in experimental osteoarthritis. In this study, we investigated the role of TRPA1 in joint inflammation, focusing on the pro-inflammatory cytokine interleukin-6 (IL-6). We utilized cartilage/chondrocytes from wild-type (WT) and TRPA1 knockout (KO) mice, along with primary chondrocytes from OA patients. The results show that TRPA1 regulates the synthesis of the OA-driving inflammatory cytokine IL-6 in chondrocytes. IL-6 was highly expressed in WT chondrocytes, and its expression, along with the expression of IL-6 family cytokines leukemia inhibitory factor (LIF) and IL-11, were significantly downregulated by TRPA1 deficiency. Furthermore, treatment with the TRPA1 antagonist significantly downregulated the expression of IL-6 in chondrocytes from WT mice and OA patients. The results suggest that TRPA1 is involved in the upregulation of IL-6 production in chondrocytes. These findings together with previous results on the expression and functions of TRPA1 in cellular and animal models point to the role of TRPA1 as a potential mediator and novel drug target in osteoarthritis. publishedVersion

Walnut contains many nutrients and bioactive components such as essential fatty acids, polyphenols, fiber, ɤ-tocopherol, folate, minerals, and vegetable protein, and has therefore been regarded as a natural functional food. Walnut-enriched diets have been demonstrated to be useful for heart health, cancer prevention, and metabolic disorders owing to their anti-oxidative and anti-inflammatory properties as well as for the maintenance of a healthy metabolism and immune function. Walnut extracts, either phenolic or lipid, also demonstrated the health effects in animal and cultured cell studies. More recently, the beneficial effects of walnut consumption on non-alcoholic fatty liver disease, which is a hepatic manifestation of obesity, hyperlipidemia, type 2 diabetes mellitus, and metabolic syndrome with substantial hepatic accumulation of triglyceride, have been proposed because walnut and a walnut-containing diet can modulate the etiologic mechanism such as ameliorating systemic and hepatic dyslipidemia, reducing lipotoxicity and inflammation, enhancing immune function, and maintaining gut microbiota balance. Through the extensive literature review we discuss the preventive roles of walnut in the development and progression of non-alcoholic fatty liver disease (NAFLD) and provide mechanistic insights into these effects.

This study concerns the safety factor and the reliability calculation for structural codes. The Eurocodes are used as a reference. Safety factor calculation is a demanding task which necessitates using an appropriate root-solving algorithm with a sufficient numerical accuracy. This article introduces a simple algorithm to calculate the safety factors directly, as previously there has been no means to control the accuracy. Presently, the safety factors are defined indirectly through the reliability index. The basic safety factor calculation is presented here in six different equations with the same outcome but differences regarding the numerical calculation, which provides a method to check the accuracy and select a proper equation for the root solver. The safety factor calculation for the permanent and the variable load in the Eurocodes is based on the independent, i.e., random, load combination and single load pairs. The current approach of safety factor calculation applied in the Eurocodes is disclosed here. Simple analytical equations based on the convolution equation are presented. Those can be used instead of the computer programs applied currently. publishedVersion

The early signaling events involved in oxidant recognition and triggering of oxidant-specific defense mechanisms to counteract oxidative stress still remain largely elusive. Our discovery driven comparative proteomics analysis revealed unique early signaling response of the yeast Saccharomyces cerevisiae on the proteome level to oxidants with a different mechanism of action as early as 3 min after treatment with four oxidants, namely H2O2, cumene hydroperoxide (CHP), and menadione and diamide, when protein abundances were compared using label-free quantification relying on a high-resolution mass analyzer (Orbitrap). We identified significant regulation of 196 proteins in response to H2O2, 569 proteins in response to CHP, 369 proteins in response to menadione and 207 proteins in response to diamide. Only 17 proteins were common across all treatments, but several more proteins were shared between two or three oxidants. Pathway analyses revealed that each oxidant triggered a unique signaling mechanism associated with cell survival and repair. Signaling pathways mostly regulated by oxidants were Ran, TOR, Rho, and eIF2. Furthermore, each oxidant regulated these pathways in a unique way indicating specificity of response to oxidants having different modes of action. We hypothesize that interplay of these signaling pathways may be important in recognizing different oxidants to trigger different downstream MAPK signaling cascades and to induce specific responses.

This study was supported by Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq, Proc. PDE 204792/2018-5 and PQ 307382/2019-2), Funda??o de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS, 16/2551-000485-7) and the Biotechnology and Biological Sciences Research Council UK (BB/K008226/1). University of Kent. School of Biosciences. Canterbury, UK; Universidade Federal do Rio Grande do Sul. Instituto de Bioci?ncias. Departamento de Gen?tica. Laborat?rio de Citogen?tica e Evolu??o. Rio Grande do Sul, RS, Brazil. Universidade Federal do Pampa. Laborat?rio de Diversidade Gen?tica Animal. Rio Grande do Sul, RS, Brazil. Universidade Federal do Pampa. Laborat?rio de Diversidade Gen?tica Animal. Rio Grande do Sul, RS, Brazil. Universidade Federal do Rio Grande do Sul. Instituto de Bioci?ncias. Departamento de Gen?tica. Laborat?rio de Citogen?tica e Evolu??o. Rio Grande do Sul, RS, Brazil. Universidade Federal de S?o Carlos. Centro de Ci?ncias Biol?gicas e da Sa?de. Departamento de Gen?tica e Evolu??o. Laborat?rio de Citogen?tica de Peixes. S?o Carlos, SP, Brazil. Universidade Federal de S?o Carlos. Centro de Ci?ncias Biol?gicas e da Sa?de. Departamento de Gen?tica e Evolu??o. Laborat?rio de Citogen?tica de Peixes. S?o Carlos, SP, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Par?. Instituto de Ci?ncias Exatas e Naturais. Bel?m, PA, Brazil. University of Kent. School of Biosciences. Canterbury, UK. University of Kent. School of Biosciences. Canterbury, UK. Abstract: Although cytogenetics studies in cuckoos (Aves, Cuculiformes) have demonstrated an interesting karyotype variation, such as variations in the chromosome morphology and diploid number, their chromosome organization and evolution, and relation with other birds are poorly understood. Hence, we combined conventional and molecular cytogenetic approaches to investigate chromosome homologies between chicken and the smooth-billed ani (Crotophaga ani). Our results demonstrate extensive chromosome reorganization in C. ani, with interchromosomal rearrangements involving macro and microchromosomes. Intrachromosomal rearrangements were observed in some macrochromosomes, including the Z chromosome. The most evolutionary notable finding was a Robertsonian translocation between the microchromosome 17 and the Z chromosome, a rare event in birds. Additionally, the simple short repeats (SSRs) tested here were preferentially accumulated in the microchromosomes and in the Z and W chromosomes, showing no relationship with the constitutive heterochromatin regions, except in the W chromosome. Taken together, our results suggest that the avian sex chromosome is more complex than previously postulated and revealed the role of microchromosomes in the avian sex chromosome evolution, especially cuckoos.

The fungal cytochrome P450 enzyme sterol 14α-demethylase (SDM) is a key enzyme in the ergosterol biosynthesis pathway. The binding of azoles to the active site of SDM results in a depletion of ergosterol, the accumulation of toxic intermediates and growth inhibition. The prevalence of azole-resistant strains and fungi is increasing in both agriculture and medicine. This can lead to major yield loss during food production and therapeutic failure in medical settings. Diverse mechanisms are responsible for azole resistance. They include amino acid (AA) substitutions in SDM and overexpression of SDM and/or efflux pumps. This review considers AA affecting the ligand-binding pocket of SDMs with a primary focus on substitutions that affect interactions between the active site and the substrate and inhibitory ligands. Some of these interactions are particularly important for the binding of short-tailed azoles (e.g., voriconazole). We highlight the occurrence throughout the fungal kingdom of some key AA substitutions. Elucidation of the role of these AAs and their substitutions may assist drug design in overcoming some common forms of innate and acquired azole resistance.

Plasma membrane (PM) hyperpolarization, increased intracellular pH (pHi), and changes in intracellular calcium concentration ([Ca2+]i) are physiological events that occur during human sperm capacitation. These parameters are potential predictors of successful outcomes for men undergoing artificial reproduction techniques (ARTs), but methods currently available for their determination pose various technical challenges and limitations. Here, we developed a novel strategy employing time-lapse flow cytometry (TLFC) to determine capacitation-related membrane potential (Em) and pHi changes, and progesterone-induced [Ca2+]i increases. Our results show that TLFC is a robust method to measure absolute Em and pHi values and to qualitatively evaluate [Ca2+]i changes. To support the usefulness of our methodology, we used sperm from two types of normozoospermic donors: known paternity (subjects with self-reported paternity) and no-known paternity (subjects without self-reported paternity and no known fertility problems). We found relevant differences between them. The incidences of membrane hyperpolarization, pHi alkalinization, and increased [Ca2+]i were consistently high among known paternity samples (100%, 100%, and 86%, respectively), while they varied widely among no-known paternity samples (44%, 17%, and 45%, respectively). Our results indicate that TLFC is a powerful tool to analyze key physiological parameters of human sperm, which pending clinical validation, could potentially be employed as fertility predictors.

A series of linear profiles of the elements of the enamel in human molar teeth were made with the use of an electron microprobe and a Raman microscope. It is postulated that the enamel can be treated as the superposition of variable &ldquo, overbuilt&rdquo, enamel on the stable &ldquo, core&rdquo, enamel at the macro-, micro- and nanoscale level. The excessive values characterize the &ldquo, overbuilt enamel&rdquo, All the profiles of excessive parameters along the enamel thickness from the enamel surface to the dentin enamel junction (DEJ) can be approximated very precisely with the use of exponential functions, where Ca, P, Cl and F spatial profiles are decaying while Mg, Na, K and CO32&minus, ones are growing distributions. The &ldquo, apatite formed on the boundary with DEJ, enriched in Na, Mg, OH and carbonates, reacts continuously with Ca, Cl and F, passing into an acid-resistant form of the &ldquo, enamel. The apparent phases arriving in boundary regions of the &ldquo, were proposed. Microdiffraction measurements reveal relative variation of energy levels during enamel transformations. Our investigations are the milestones for a further new class of biomaterial and nanomaterial development for biomedical applications.

Xanthomonas campestris pv. campestris is known as the causative agent of black rot disease, which attacks mainly crucifers, severely lowering their global productivity. One of the main virulence factors of this pathogen is its capability to penetrate and form biofilm structures in the xylem vessels. The discovery of novel approaches to crop disease management is urgent and a possible treatment could be aimed at the eradication of biofilm, although anti-biofilm approaches in agricultural microbiology are still rare. Considering the multifactorial nature of biofilm, an effective approach against Xanthomonas campestris implies the use of a multi-targeted or combinatorial strategy. In this paper, an anti-biofilm strategy based on the use of fatty acids and the bacteriophage (Xcc&phi, 1)-hydroxyapatite complex was optimized against Xanthomonas campestris mature biofilm. The synergic action of these elements was demonstrated and the efficient removal of Xanthomonas campestris mature biofilm was also proven in a flow cell system, making the proposed approach an effective solution to enhance plant survival in Xanthomonas campestris infections. Moreover, the molecular mechanisms responsible for the efficacy of the proposed treatment were explored.

The growing competitiveness of the market, coupled with the increase in automation driven with the advent of Industry 4.0, highlights the importance of maintenance within organizations. At the same time, the amount of data capable of being extracted from industrial systems has increased exponentially due to the proliferation of sensors, transmission devices and data storage via Internet of Things. These data, when processed and analyzed, can provide valuable information and knowledge about the equipment, allowing a move towards predictive maintenance. Maintenance is fundamental to a company&rsquo, s competitiveness, since actions taken at this level have a direct impact on aspects such as cost and quality of products. Hence, equipment failures need to be identified and resolved. Artificial Intelligence tools, in particular Machine Learning, exhibit enormous potential in the analysis of large amounts of data, now readily available, thus aiming to improve the availability of systems, reducing maintenance costs, and increasing operational performance and support in decision making. In this dissertation, Artificial Intelligence tools, more specifically Machine Learning, are applied to a set of data made available online and the specifics of this implementation are analyzed as well as the definition of methodologies, in order to provide information and tools to the maintenance area.

Streptococcus mutans is the main early colonizing cariogenic bacteria because it recognizes salivary pellicle receptors. The Antigen I/II (Ag I/II) of S. mutans is among the most important adhesins in this process, and is involved in the adhesion to the tooth surface and the bacterial co-aggregation in the early stage of biofilm formation. However, this protein has not been used as a target in a virtual strategy search for inhibitors. Based on the predicted binding affinities, drug-like properties and toxicity, molecules were selected and evaluated for their ability to reduce S. mutans adhesion. A virtual screening of 883,551 molecules was conducted, cytotoxicity analysis on fibroblast cells, S. mutans adhesion studies, scanning electron microscopy analysis for bacterial integrity and molecular dynamics simulation were also performed. We found three molecules ZINC19835187 (ZI-187), ZINC19924939 (ZI-939) and ZINC19924906 (ZI-906) without cytotoxic activity, which inhibited about 90% the adhesion of S. mutans to polystyrene microplates. Molecular dynamic simulation by 300 nanoseconds showed stability of the interaction between ZI-187 and Ag I/II (PDB: 3IPK). This work provides new molecules that targets Ag I/II and have the capacity to inhibit in vitro the S. mutans adhesion on polystyrene microplates.

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, diseases such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis and Wilson’s disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease of other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver fibrosis.

Tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis (Mtb). According to the World Health Organization, an estimated 10 million people developed TB in 2018. The occurrence of drug-resistant TB demands therapeutic agents with novel mechanisms of action. Antivirulence is an alternative strategy that targets bacterial virulence factors instead of central growth pathways to treat disease. Mycobacterium protein tyrosine phosphatases, mPTPA and mPTPB, are secreted by Mtb into the cytoplasm of macrophages and are required for survival and growth of infection within the host. Here we present recent advances in understanding the roles of mPTPA and mPTPB in the pathogenesis of TB. We also focus on potent, selective, and well-characterized small molecule inhibitors reported in the last decade for mPTPA and mPTPB.

Purpose: In order to study novel therapeutic approaches taking advantage of natural compounds showing anticancer and anti-proliferative effects, we focused our interest on S-adenosyl-l-methionine, a naturally occurring sulfur-containing nucleoside synthesized from adenosine triphosphate and methionine by methionine adenosyltransferase, and its potential in overcoming drug resistance in colon cancer cells devoid of p53. Results: In the present study, we demonstrated that S-adenosyl-l-methionine overcomes uL3-mediated drug resistance in p53 deleted colon cancer cells. In particular, we demonstrated that S-adenosyl-l-methionine causes cell cycle arrest at the S phase, inhibits autophagy, augments reactive oxygen species, and induces apoptosis in these cancer cells. Conclusions: Results reported in this paper led us to propose S-adenosyl-l-methionine as a potential promising agent for cancer therapy by examining p53 and uL3 profiles in tumors to yield a better clinical outcomes.

Immune Thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibodies-mediated platelet destruction, a prevalence of M1 pro-inflammatory macrophage phenotype and an elevated T helper 1 and T helper 2 lymphocytes (Th1/Th2) ratio, resulting in impairment of inflammatory profile and immune response. Macrophages are immune cells, present as pro-inflammatory classically activated macrophages (M1) or as anti-inflammatory alternatively activated macrophages (M2). They have a key role in ITP, acting both as effector cells, phagocytizing platelets, and, as antigen presenting cells, stimulating auto-antibodies against platelets production. Eltrombopag (ELT) is a thrombopoietin receptor agonist licensed for chronic ITP to stimulate platelet production. Moreover, it improves T and B regulatory cells functions, suppresses T-cells activity, and inhibits monocytes activation. We analyzed the effect of ELT on macrophage phenotype polarization, proposing a new possible mechanism of action. We suggest it as a mediator of macrophage phenotype switch from the M1 pro-inflammatory type to the M2 anti-inflammatory one in paediatric patients with ITP, in order to reduce inflammatory state and restore the immune system function. Our results provide new insights into the therapy and the management of ITP, suggesting ELT also as immune-modulating drug.

International audience; The advent of telerobotic systems has revolutionized various aspects of the industry and human life. This technology is designed to augment human sensorimotor capabilities to extend them beyond natural competence. Classic examples are space and underwater applications when distance and access are the two major physical barriers to be combated with this technology. In modern examples, telerobotic systems have been used in several clinical applications, including teleoperated surgery and telerehabilitation. In this regard, there has been a significant amount of research and development due to the major benefits in terms of medical outcomes. Recently telerobotic systems are combined with advanced artificial intelligence modules to better share the agency with the operator and open new doors of medical automation. In this review paper, we have provided a comprehensive analysis of the literature considering various topologies of telerobotic systems in the medical domain while shedding light on different levels of autonomy for this technology, starting from direct control, going up to command-tracking autonomous telerobots. Existing challenges, including instrumentation, transparency, autonomy, stochastic communication delays, and stability, in addition to the current direction of research related to benefit in telemedicine and medical automation, and future vision of this technology, are discussed in this review paper

An important as well as challenging task in modern applications is the management and processing with very short delays of large data volumes. It is quite often, that the capabilities of individual machines are exceeded when trying to manage such large data volumes. In this regard, it is important to develop efficient task scheduling algorithms, which reduce the stream processing costs. What makes the situation more difficult is the fact that the applications as well as the processing systems are prone to changes during runtime: processing nodes may be down, temporarily or permanently, more resources may be needed by an application, and so on. Therefore, it is necessary to develop dynamic schedulers, which can effectively deal with these changes during runtime. In this work, we provide a fast and fair task migration policy while maintaining load balancing and low latency times. The experimental results have shown that our scheme offers better load balancing and reduces the overall latency compared to the state of the art strategies, due to the stepwise communication and the pipeline based processing it employs.

The FEL integral equation is reviewed here and is studied under different contexts, accounting for diverse physical regimes. We include higher order harmonics and saturation effects, and explain the origin of scaling relations, widely exploited to describe either FEL dynamics or nonnlinear harmonic generation.

Despite substantial progress in cancer therapy, colorectal cancer (CRC) is still the third leading cause of cancer death worldwide, mainly due to the acquisition of resistance and disease recurrence in patients. Growing evidence indicates that deregulation of hormone signaling pathways and their cross-talk with other signaling cascades inside CRC cells may have an impact on therapy resistance. MicroRNAs (miRNAs) are small conserved non-coding RNAs thatfunction as negative regulators in many gene expression processes. Key studies have identified miRNA alterations in cancer progression and drug resistance. In this review, we provide a comprehensive overview and assessment of miRNAs role in hormone signaling pathways in CRC drug resistance and their potential as future targets for overcoming resistance to treatment.

Reminder cues can destabilize consolidated memories, rendering them modifiable before they return to a stable state through the process of reconsolidation. Older and stronger memories resist this process and require the presentation of reminders along with salient novel information in order to destabilize. Previously, we demonstrated in rats that novelty-induced object memory destabilization requires acetylcholine (ACh) activity at M1 muscarinic receptors. Other research predominantly has focused on glutamate, which modulates fear memory destabilization and reconsolidation through GluN2B- and GluN2A-containing NMDARs, respectively. In the current study, we demonstrate the same dissociable roles of GluN2B- and N2A-containing NMDARs in perirhinal cortex (PRh) for object memory destabilization and reconsolidation when boundary conditions are absent. However, neither GluN2 receptor subtype was required for novelty-induced destabilization of remote, resistant memories. Furthermore, GluN2B and GluN2A subunit proteins were upregulated selectively in PRh 24 h after learning, but returned to baseline by 48 h, suggesting that NMDARs, unlike muscarinic receptors, have only a temporary role in object memory destabilization. Indeed, activation of M1 receptors in PRh at the time of reactivation effectively destabilized remote memories despite inhibition of GluN2B-containing NMDARs. These findings suggest that cholinergic activity at M1 receptors overrides boundary conditions to destabilize resistant memories when other established mechanisms are insufficient.

The bonding ability between basalt fiber bundle and asphalt mortar has a great influence on the properties of basalt fiber reinforced asphalt mixtures, yet the studies about the bonding between them is very limited. In this paper, a new test instrument called fiber-asphalt pulling machine and a new index called the nominal bonding stress (NBS) were designed and adopted to test and reveal the bonding between basalt fiber bundle and asphalt mortar. The procedures and rationality analysis of this new experiment was specified in this paper. In order to verify the reliability of the NBS index, the NBS values derived from this new test method and the rheological property indexes values of asphalt mortar under different powder&ndash, cement ratios were adopted to analyze the correlation between them. Two kinds of basalt fibers produced by two different manufacturers were adopted to conduct the parallel experiment. The results show that the nominal bonding stress between basalt fiber and asphalt mortar derived from this new test has a great correlation with the rheological properties of asphalt mortar, which also proves the credibility of this new test method and the NBS index.

Elastomeric bearings are commonly used in base-isolation systems to protect the structures from earthquake damages. Their design is usually developed by using nonlinear models where only the effects of shear and compressive loads are considered, but uncertainties still remain about consequences of the tensile loads produced by severe earthquakes like the near-fault ones. The present work aims to highlight the relapses of tension on the response of bearings and superstructure. To this end, three-, seven- and ten-storey r.c. framed buildings are designed in line with the current Italian seismic code, with a base-isolation system constituted of High-Damping-Rubber Bearings (HDRBs) designed for three values of the ratio between the vertical and horizontal stiffnesses. Experimental and analytical results available in literature are used to propose a unified nonlinear model of the HDRBs, including cavitation and post-cavitation of the elastomer. Nonlinear incremental dynamic analyses of the test structures are carried out using a homemade computer code, where other models of HDRBs considering only some nonlinear phenomena are implemented. Near-fault earthquakes with comparable horizontal and vertical components, prevailing horizontal component and prevailing vertical component are considered as seismic input. Numerical results highlight that a precautionary estimation of response parameters of the HDRBs is attained referring to the proposed model, while its effects on the nonlinear response of the superstructure are less conservative.

(1→3)-β-glucan (BDG) testing as an adjunct in the diagnosis of invasive fungal disease (IFD) has been in use for nearly three decades. While BDG has a very high negative predictive value in this setting, diagnostic false positives may occur, limiting specificity and positive predictive value. Although results may be diagnostically false positive, they are analytically correct, due to the presence of BDG in the circulation. This review surveys the non-IFD causes of elevated circulating BDG. These are in the main, iatrogenic patient contamination through the use of BDG-containing medical devices and parenterally-delivered materials as well as translocation of intestinal luminal BDG due to mucosal barrier injury. Additionally, infection with Nocardia sp. may also contribute to elevated circulating BDG. Knowledge of the factors which may contribute to such non-IFD-related test results can improve the planning and interpretation of BDG assays and permit investigational strategies, such as serial sampling and BDG clearance evaluation, to assess the likelihood of contamination and improve patient care.

Beetle luciferases produce bioluminescence (BL) colors ranging from green to red, having been extensively used for many bioanalytical purposes, including bioimaging of pathogen infections and metastasis proliferation in living animal models and cell culture. For bioimaging purposes in mammalian tissues, red bioluminescence is preferred, due to the lower self-absorption of light at longer wavelengths by hemoglobin, myoglobin and melanin. Red bioluminescence is naturally produced only by Phrixothrix hirtus railroad worm luciferase (PxRE), and by some engineered beetle luciferases. However, Far-Red (FR) and Near-Infrared (NIR) bioluminescence is best suited for bioimaging in mammalian tissues due to its higher penetrability. Although some FR and NIR emitting luciferin analogs have been already developed, they usually emit much lower bioluminescence activity when compared to the original luciferin-luciferases. Using site-directed mutagenesis of PxRE luciferase in combination with 6&prime, modified amino-luciferin analogs, we finally selected novel FR combinations displaying BL ranging from 636&ndash, 655 nm. Among them, the combination of PxRE-R215K mutant with 6&prime, (1-pyrrolidinyl)luciferin proved to be the best combination, displaying the highest BL activity with a catalytic efficiency ~2.5 times higher than the combination with native firefly luciferin, producing the second most FR-shifted bioluminescence (650 nm), being several orders of magnitude brighter than commercial AkaLumine with firefly luciferase. Such combination also showed higher thermostability, slower BL decay time and better penetrability across bacterial cell membranes, resulting in ~3 times higher in vivo BL activity in bacterial cells than with firefly luciferin. Overall, this is the brightest FR emitting combination ever reported, and is very promising for bioimaging purposes in mammalian tissues.

Ibrutinib is a small-molecule inhibitor of Bruton’s tyrosine kinase, an enzyme central in B cell development. It is indicated as a therapy for certain hematological diseases such as chronic lymphocytic leukemia (CLL), but also exerts off-target effects on several receptors and kinases. In this paper, we hypothesize that ibrutinib may suppress the tumor marker CA-125 in ovarian cancer. The hypothesis is based on an observation of CA-125 normalization in a patient with low-grade serous ovarian cancer who received ibrutinib for concurrent CLL. We propose a mechanistic model explaining this possible drug effect as a foundation for further research.

Using a data driven analysis of a high-content screen, we have uncovered new regulators of epithelial-to-mesenchymal transition (EMT) induced cell migration. Our results suggest that increased expression of miR614 can alter cell intrinsic gene expression to enhance single cell and collective migration in multiple contexts. Interestingly, miR614 specifically increased the expression of the EMT transcription factor Slug while not altering existing epithelial character or inducing other canonical EMT regulatory factors. Analysis of two different cell lines identified a set of genes whose expression is altered by the miR614 through direct and indirect mechanisms. Prioritization driven by functional testing of 25 of the miR614 suppressed genes uncovered the mitochondrial small GTPase Miro1 and the transmembrane protein TAPT1 as miR614 suppressed genes that inhibit migration. Notably, the suppression of either Miro1 or TAPT1 was sufficient to increase Slug expression and the rate of cell migration. Importantly, reduced TAPT1 expression correlated with an increased risk of relapse in breast cancer patients. Together, our results reveal how increased miR614 expression and the suppression of TAPT1 and Miro1 modulate the EMT state and migratory properties of breast cancer cells.

Accountability refers to the need of individuals or organizations to account for their activities, accept responsibility, and disclose results in a transparent manner. Nowadays, the pervasivity of digital systems is making increasingly critical security, reliability, and trustworthiness of such services. When a service is delivered by involving different (eventually conflicting) parties, accountability could be achieved by including in digital transactions a trusted third party (TTP). Blockchain decentralizes trust, thus avoiding to rely on a single TTP. However, to deal with accountability in concrete solutions, the issue of securely integrating digital identity and Blockchain should be solved. The paper describes the results of a three-year research project merging academic and industrial expertise, to design and implement a Blockchain-based platform for service accountability integrating eIDAS-compliant Public Digital Identity. The platform has been used in several real-life contexts made available by industrial project partners, which demonstrated the effectiveness and novelty of the solution.

The prevalence of chronic kidney disease (CKD) is increasing worldwide, and the mortality rate continues to be unacceptably high. The biomarkers currently used in clinical practice are considered relevant when there is already significant renal impairment compromising the early use of potentially successful therapeutic interventions. More sensitive and specific biomarkers to detect CKD earlier on and improve patients' prognoses are an important unmet medical need. The aim of this review is to summarize the recent literature on new promising early CKD biomarkers of renal function, tubular lesions, endothelial dysfunction and inflammation, and on the auspicious findings from metabolomic studies in this field. Most of the studied biomarkers require further validation in large studies and in a broad range of populations in order to be implemented into routine CKD management. A panel of biomarkers, including earlier biomarkers of renal damage, seems to be a reasonable approach to be applied in clinical practice to allow earlier diagnosis and better disease characterization based on the underlying etiologic process. info:eu-repo/semantics/publishedVersion

Emissions from the household sector are the most significant source of air pollution in Poland, one of the most polluted countries in the EU. Estimated health impacts of the reduction of these emissions under three scenarios are presented. The EMEP4PL model and base year emission inventory were used to estimate average annual PM10 and PM2.5 concentrations with spatial resolution of 4 km &times, 4 km. The change in emissions under each of the scenarios was based on data from a survey on household boilers and insulation. Scenario 1 included replacement of all poor-quality coal-fired boilers with gas boilers, Scenario 2 included replacement of all poor-quality coal-fired boilers with low-emission boilers but still using solid fuels, and Scenario 3 included the thermal refurbishment of houses with the worst insulation. Impacts on the following health parameters were estimated: premature deaths (PD), Chronic Bronchitis (CB), Bronchitis in Children (BiC) and Work Days Lost (WDL). The concentration&ndash, response functions recommended by the WHO HRAPIE project were used. The analysis was conducted for two regions: Lower Silesia and Lodzkie province. The largest reduction of health impact was observed for Scenario 1. For Lower Silesia, the annual PD decreased by 1122 (34.3%), CB by 1516 (26.6%), BiC by 9602 (27.7%) and WDL by 481k (34.7%). For Lodzkie province, the largest impacts were estimated as decreases in PD by 1438 (29.9%), CB by 1502 (25.3%), BiC by 9880 (26.8%) and WDL by 669k (30.4%).

In this work, a new design for a real-time noninvasive metamaterial sensor, based on a corona-shaped resonator, is proposed. The sensor was designed numerically and fabricated experimentally in order to be utilized for efficient detection of glucose in aqueous solutions such as water and blood. The sensor was inspired by a corona in-plane-shaped design with the presumption that its circular structure might produce a broader interaction of the electromagnetic waves with the glucose samples. A clear shift in the resonance frequency was observed for various glucose samples, which implies that the proposed sensor has a good sensitivity and can be easily utilized to distinguish any glucose concentration, even though their dielectric coefficients are close. Results showed a superior performance in terms of resonance frequency shift (1.51 GHz) and quality factor (246) compared to those reported in the literature. The transmission variation level ∆|S21| was investigated for glucose concentration in both water and blood. The sensing mechanism was elaborated through the surface current, electric field and magnetic field distributions on the corona resonator. The proposed metamaterials sensor is considered to be a promising candidate for biosensor and medicine applications in human glycaemia monitoring.

C and N are the most important essential elements constituting organic compounds in plants. The shoots and roots depend on each other by exchanging C and N through the xylem and phloem transport systems. Complex mechanisms regulate C and N metabolism to optimize plant growth, agricultural crop production, and maintenance of the agroecosystem. In this paper, we cover the recent advances in understanding C and N metabolism, regulation, and transport in plants, as well as their underlying molecular mechanisms. Special emphasis is given to the mechanisms of starch metabolism in plastids and the changes in responses to environmental stress that were previously overlooked, since these changes provide an essential store of C that fuels plant metabolism and growth. We present general insights into the system biology approaches that have expanded our understanding of core biological questions related to C and N metabolism. Finally, this review synthesizes recent advances in our understanding of the trade-off concept that links C and N status to the plant’s response to microorganisms.

A multimodal therapeutic approach involving radiotherapy is required when treating head and neck squamous cell carcinoma. However, radiotherapy is restricted due to its high risk for damages to the surrounding healthy tissue of the treated area. Tissue regeneration and wound healing is promoted by the survival and regenerative capacities of tissue-resident or invading stem cells. Mesenchymal stem cells (MSCs) exhibit a promising therapeutic potential in the field of cell-based tissue engineering and regenerative medicine due to their immunomodulatory properties and differentiation capacity. However, the generation of MSCs for therapeutic applications is still a major challenge. We aimed to produce highly homogeneous induced pluripotent stem cell-derived mesenchymal stem cells (iP-MSCs) in an autologous manner from initially isolated human mucosa mesenchymal stem cells (mMSCs) of the upper respiratory tract. Therefore, mMSCs were reprogrammed into induced pluripotent stem cells (iPSCs) by non-integrative chromosomal technologies and differentiated into corresponding iP-MSCs. We demonstrated that mMSCs and iP-MSCs show similar cell characteristics in terms of morphology, clonogenic potential, differentiation, and surface phenotype. Moreover, iP-MSCs demonstrated related immunosuppressive capacity as mMSCs including the secretion of cytokines, and T cell inhibition. Therefore, generating iP-MSCs in an autologous manner may be a novel personalized treatment option in regenerative medicine.

The enteric nervous system (ENS) constitutes the largest part of the peripheral nervous system. In recent years, ENS development and its neurogenetic capacity in homeostasis and allostasishave gained increasing attention. Developmentally, the neural precursors of the ENS are mainly derived from vagal and sacral neural crest cell portions. Furthermore, Schwann cell precursors, as well as endodermal pancreatic progenitors, participate in ENS formation. Neural precursorsenherite three subpopulations: a bipotent neuron-glia, a neuronal-fated and a glial-fated subpopulation. Typically, enteric neural precursors migrate along the entire bowel to the anal end, chemoattracted by glial cell-derived neurotrophic factor (GDNF) and endothelin 3 (EDN3) molecules. During migration, a fraction undergoes differentiation into neurons and glial cells. Differentiation is regulated by bone morphogenetic proteins (BMP), Hedgehog and Notch signalling. The fully formed adult ENS may react to injury and damage with neurogenesis and gliogenesis. Nevertheless, the origin of differentiating cells is currently under debate. Putative candidates are an embryonic-like enteric neural progenitor population, Schwann cell precursors and transdifferentiating glial cells. These cells can be isolated and propagated in culture as adult ENS progenitors and may be used for cell transplantation therapies for treating enteric aganglionosis in Chagas and Hirschsprung’s diseases.

Dicarbonyl compounds, including methylglyoxal (MGO) and glyoxal (GO), are mainly formed as byproducts of glucose metabolism. The main glyoxalase system consists of glyoxalase I and II (Glo1 and Glo2) and is the main enzyme involved in the detoxification of dicarbonyl stress, which occurs as an accumulation of MGO or GO due to decreased activity or expression of Glo1. Dicarbonyl stress is a major cause of cellular and tissue dysfunction that causes various health issues, including diabetes, aging, and cancer. The skin is the largest organ in the body. In this review, we discuss the role of the glyoxalase system in the progression of skin aging, and more importantly, skin malignancies. We also discuss the future prospects of the glyoxalase system in other skin abnormalities such as psoriasis and vitiligo, including hyperpigmentation. Finally, in the present review, we suggest the role of glyoxalase in the progression of skin aging and glyoxalase system as a potential target for anticancer drug development for skin cancer.

This study aimed to determine the applicability of using selected libraries of computing environment R to establish the coefficient of self-similarity. R environment is an analytical environment with rich functionality that is used in many research and practical works concerning data analysis and knowledge discovery. Such an issue is significant in the context of contemporary wide area computer networks and the emerging type of network infrastructure IoT. This originates directly from the new nature of IoT traffic, which also has a substantial impact on Industry 4.0. It provides built-in operations facilitating data processing. The Hurst coefficient is used to evaluate traffic behavior and analyze its character. The study analyzed two cases of IoT network traffic: high and low intensity. For different sizes of time windows, we dermined the statistical Hurst exponent and compared it with standard, smoothed, and Robinson methods. The accuracy of the methods used was evaluated. Spectral regression graphs were additionally generated for selected motion variants. The obtained results were verified by Higuchi and Aggvar methods.

Portunus trituberculatus is an important invertebrate species distributed in the Yangtze Estuary. However, its biomass and enrichment have been affected seriously by ongoing human activity in recent decades. The length-based Bayesian biomass estimator (LBB) is a novel and potent method to estimate the stocks for most commercial fishes and invertebrates in offshore using only length and frequency data. In this study, the results showed that the ratio of current exploited biomass relative to unexploited biomass (B/B0) was smaller than relative biomass capable of producing maximum sustainable yields (BMSY/B0) after handling of the catches of the P. trituberculatus collected from the Yangtze Estuary in 2018 using the LBB method. Therefore, this evidence indicated that the biomass of the swimming crab was relatively low as a result of the overfishing in this water area and the catches of the crabs should be controlled at a reasonable level in the future. Meanwhile, LBB is a promising method providing a theoretical basis for the management and protection of fishery resources.