Production of energy is a main task of cancer cells metabolism, since costs of duplicating are enormous. Although energy is derived in cells by dismantling carbon to carbon bonds of any macronutrient, cancer nutritional needs for energetic purposes have been studied primarily as dependent on glycolysis. Since the end of the last century, awareness of dependence of cancer metabolism on amino acids not only for protein syntheses but also for matching energy needs has grown. The roles of specific amino acids, like glutamine, glycine and serine have been explored in different experimental conditions and reviewed. Moreover, there are epidemiological evidences that some amino acids used as supplement for therapeutic reasons (the branched chain ones) may reduce incidence of liver cancer, and some molecular mechanism has been proposed as functional to their protective action. On the contrary, metabolic signature of some pathology connected with increased risk of cancer, like prolonged hyperinsulinemia in insulin resistant patients, is signed by plasma elevated levels of the same branched chain amino acids, posing puzzling questions to clinicians. Most recently, peculiar formulations of amino acids, deeply different if compared to amino acids compositions normally present in foods, have shown the power to master epigenetics slowing growth or driving cancer cells to apoptotic death, while being even beneficial for normal cells and for animals health and life span. In this review, we will analyze and try to disentangle some of the many knots dealing with complexities of amino acids biology and linked to cancer metabolism.

South Korea proposed reducing greenhouse gas emissions by 37% compared to the expected emissions by 2030 as the POST-2020 greenhouse gas reduction target. Electric vehicle distribution in the public sector is essential to achieve the carbon dioxide reduction target for transportation. In particular, when buses with internal combustion engines, which travel long distances and contribute substantially to greenhouse gas emissions, are replaced with electric buses, it is expected that greenhouse gas emissions will be significantly reduced. There are three types of electric buses with different power supply systems: a plug-in type in which power is supplied when a plug is inserted, a battery-swapping type in which a battery mounted on top of the vehicle is swapped at a swapping station, and a wireless type in which the battery is wirelessly charged through self-induction at a charging facility installed on the road. Vehicles of each charging type have different advantages and disadvantages. The performance, charging type, battery capacity, and operating environment of electric buses are mutually related parameters that must be considered when introducing such vehicles. Therefore, the optimal charging type must be selected according to the operating environment to enable the widespread use of electric buses. As such, this report proposes the optimal charging type according to the operating environment of public-sector electric vehicles.

A highly crystallized monoclinic-scheelite type BiVO4 powders were successfully synthesized by solvothermal method. The as-synthesized BiVO4 powders were characterized by XRD, FE-SEM, Raman spectroscopy, UV-vis DRS spectroscopy and TA-PL. From the XRD data and Raman spectra, the monoclinic-scheelite phase BiVO4 sample can be obtained at higher solvothermal synthesis temperature more than 140 oC. The preparation conditions such as, the Bi/V molar ratio and synthesis temperature, have significantly effects on the morphologies of the BiVO4 samples. BVO2 sample shows the highest PL peak, which has the highest formation rate of OH radicals and the highest photocatalytic activity. This result suggests that the formation rate of OH radicals shows a good correlation with the photocatalytic activity.

The combination of freeze-dried aronia, red ginseng, ultraviolet-irradiated shiitake mushroom and natokinase (AGM; 3.4: 4.1: 2.4: 0.1) was examined to evaluate its effects on insulin resistance, insulin secretion and gut microbiome in a non-obese type 2 diabetic animal model. Pancreatectomized (Px) rats were provided high fat diets supplemented with either of 1) 0.5 g AGM (AGM-L), 2) 1 g AGM (AGM-H), 3) 1 g dextrin (control), or 4) 1g dextrin with 120 mg metformin (positive-control) per kg body weight for 12 weeks. AGM (1 g) contained 6.22 mg cyanidin-3-galactose, 2.5 mg ginsenoside Rg3 and 0.6 mg β-glucan. Px rats had decreased bone mineral density in the lumbar spine and femur and lean body mass in the hip and leg compared to the normal-control and AGM-L and AGM-H prevented the decrease. Visceral fat mass was lower in the control group than the normal-control group and its decrease was smaller by AGM-L and AGM-H. HOMA-IR was lower in descending order of the control, positive-control, AGM-L, AGM-H and normal-control groups. Glucose tolerance was deteriorated in the control group and it was improved by AGM-L and AGM-H more than in the positive-control group. Glucose tolerance is associated with insulin resistance and insulin secretion. Insulin tolerance indicated insulin resistance was highly impaired in diabetic rats, but it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Insulin secretion capacity, measured by hyperglycemic clamp, was much lower in the control group than the normal-control group and it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Diabetes modulated the composition of gut microbiome and AMG prevented the modulation of gut microbiome. In conclusion, AGM improved glucose metabolism by potentiating insulin secretion and reducing insulin resistance in insulin deficient type 2 diabetic rats. The improvement of diabetic status alleviated body composition changes and prevented changes of gut microbiome composition.

Metformin use in pregnancy is increasing worldwide as randomised controlled trial (RCT) evidence is emerging demonstrating its safety and efficacy. The Metformin in Gestational Diabetes (MiG) RCT changed practice in many countries demonstrating that metformin had similar pregnancy outcomes to insulin therapy with less maternal weight gain and a high degree of patient acceptability. A multicentre RCT is currently assessing the addition of metformin to insulin in pregnant women with type 2 diabetes. RCT evidence is also available for the use of metformin for women with Polycystic Ovarian Syndrome and for non-diabetic women with obesity. No evidence of an increase in congenital malformations or miscarriages has been observed even when metformin is started before pregnancy and continued to term. Body composition and metabolic outcomes at two, seven and nine years have now been reported for the offspring of mothers treated in the MiG study. In this review, we will briefly discuss the action of metformin and then consider the evidence from the key clinical trials.

In the present research, we will develop some integral inequalities of Hermite Hadamard type for differentiable η- convex function. Moreover, our results include several new and known results as special cases.

1) Background: A survey of biogenic amines profile in opened wine bottles has been established. Opened bottles of red and white wine were submitted to different temperature as well as different kind of stopper (screw cap, cork stopper) and use of vacuum devices. A total of six wine made from different variety of grapes were obtained from Polish vineyard places in different region of Poland; 2) Results: DLLME-GC-MS procedure for biogenic amines determination was validated and applied for wine samples analysis. The total content of BAs in white wines ranged from 442 µg/L to 929 µg/L, while in red wines ranged from 669 µg/L to 2244 µg/L the set of just opened wine samples. The most abundant biogenic amines in the six analysed wines were histamine and putrescine; 3) Conclusion: Considering the commercial availability of the analysed wines, there was no relationship between the presence of biogenic amines in a given wine and their availability on the market. However, it was observed that the different storage conditions employed in this experiment affect not only the biogenic amines profile, but also the pH. The results were confirmed by chemometric analysis.

Arthropod-borne flaviviruses represent human pathogens of global medical importance, against which no effective small molecule-based antiviral therapy is currently available. Arbidol (umifenovir) is a broad spectrum antiviral compound approved in Russia and China for prophylaxis and treatment of influenza. This compound showed activity against numerous DNA and RNA viruses. Its mode of action is based predominantly on the impairment of critical steps of virus-cell interaction. Here we demonstrate that arbidol possesses a micromolar inhibition activity (EC50 values ranging from 10.57 ± 0.74 to 19.16 ± 0.29 µM) in Vero cells infected with Zika virus, West Nile virus, and tick-borne encephalitis virus, three medically important representatives of arthropod-borne flaviviruses. Interestingly, no antiviral effect of arbidol is observed in porcine stable kidney cells (PS), human neuroblastoma cells (UKF-NB-6), human hepatoma cells (Huh-7 cells) indicating that the antiviral effect of arbidol is strongly cell-type dependent. Arbidol presents a significant increasing in cytotoxicity profiles when tested in various cell lines in the order: Huh-7 < HBCA < PS < UKF-NB-6 < Vero with CC50 values ranging from 18.69 ± 0.1 to 89.72 ± 0.19 µM. Antiviral activity and acceptable cytotoxicity profiles suggest that arbidol could be a promising candidate for further investigation as a potential therapeutic agent in treating flaviviral infections.

In this paper Brinkman type fluid over an infinite plate between side walls is being investigated. The flow is generated by oscillating shear stress of the bottom plate and the solutions are obtained by using Fourier integral transformation. The obtained results are presented in steady and transient states for both sin and cos shear stresses. The general solutions are reduced to some special cases corresponding, namely to the Brinkman type fluid over an infinite plate and flow of a Newtonian viscous fluid. Graphical illustrations are carried out to have in depth analysis of the involved physical parameters

Current commercially available instruments for monitoring mitochondrial respiration are incapable of single cell measurements. Therefore, we developed a three-electrode, Clark-type biosensor suitable for mitochondrial respirometry in single oocytes and embryos. The biosensor was embedded in a PMMA (polymethyl methacrylate) micro-chamber to allow investigation of single oocytes/embryos immersed in up to 100 µL of respiration buffer. The micro-chamber was completely sealed to avoid oxygen exchange between the inside of the chamber and the atmosphere, while being maintained at a temperature of 38.5 ˚C to preserve cell viability. Using amperometry, the oxygen consumption of cells inside the micro-chamber was measured as a change in output current and converted to femto-mol (fmol) oxygen consumed per second based on calibrations with known buffer oxygen concentrations. The sensor measured basal cell respiration supported by endogenous substrates, respiration associated with proton leak induced by inhibition of the adenosine triphosphate (ATP) synthase (complex V) with oligomycin, and the maximal non-coupled respiratory capacity revealed by Carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP) titration. Some potential applications of this oxygen sensor system include evaluating effects of metabolic therapies on oocyte bioenergetics, and monitoring mitochondrial function throughout oocyte maturation and blastocyst development to predict embryo viability to compliment assisted reproductive technologies

In this study, a graphene-doped porous silicon (G-doped/p-Si) substrate for low ppm H₂ gas detection by an inexpensive synthesis route was proposed as a potential noble graphene-based gas sensor material and to understand the sensing mechanism. The G-doped/p-Si gas sensor was synthesized by a simple capillary force-assisted solution dropping method on p-Si substrates, whose porosity was generated through an electrochemical etching process. G-doped/p-Si was fabricated with various graphene concentrations and exploited as a H₂ sensor operated at room temperature. The sensing mechanism of the sensor with/without graphene decoration on p-Si was proposed to elucidate the synergetic gas sensing effect generated from the interface between the graphene and p-type silicon.

An active power dispatch method for a microgrid (MG) with multi-type loads, renewable energy sources (RESs) and distributed energy storage devices (DESDs) is the focus of this paper. The MG operates in a grid-connected model, and distributed power sources contribute to the service for load demands. The outputs of multiple DESDs are controlled to optimize the active power dispatch. Our goal with optimization is to reduce the economic cost under time-of-use (TOU) price, and to adjust the excessively high or low load rate of distributed transformers (DTs) caused by the peak-valley demand and load uncertainties. To simulate a practical environment, the stochastic characteristics of multi-type loads are formulated. The transition matrix of system state is provided. Then, a finite-horizon Markov decision process (FHMDP) model is established to describe the dispatch optimization problem. A learning-based technique is adopted to search the optimal joint control policy of multiple DESDs. Finally, simulation experiments are performed to validate the effectiveness of the proposed method, and the fuzzification analysis of the method is presented.

This feature study attempts on setting a granules involving mesoscopic matter-aggregation context as a problem of passing locally by the matter-aggregating system from classical stochastic (mesoscopic limit) to a quantum description (nanoscale quantum-size effect limit). A d-dimensional entropy-production aggregation of the granules-involving matter is considered in terms of a (sub)diffusive realization. It turns out that when taking a full d-dimensional pathway of the aggregation toward the nanoscale, one is capable of disclosing a Heisenberg type (diffusional) relation, setting up an upper uncertainty bound for the (sub)diffusive very slow granules-including environment that matches the quantum limit of h/2pm (m– average mass of a granule; h – the Planck’s constant) for the diffusion coefficient of the aggregation, likely first proposed by Fürth in 1933, and qualitatively foreseen by Schrödinger some years before, both in the context of a diffusing particle cluster. The classical-quantum passage uncovered here, also termed insightfully the quantum-size effect (as borrowed from the quantum dots’ parlance), works properly for the three-dimensional (d=3) case, making use of a substantial physical fact that the (nano)granules interact readily via their surfaces with the also granular surroundings in which they are immersed. This natural observation is embodied in the basic averaging construction of the diffusion coefficient of the aggregation of interest. Certain, possibly biomedical, applications of the model can also be viewed by prospective inspection of tiny inhomogeneities in nanofibrillar and/or lamellar matter for which certain numerical realizations are plausible to prepare based on thorough nanoscale experiments.

Medicinal mushrooms, especially Ganoderma species hold immense promise for production of a wide range of bioactive compounds with various effects. The biochemical potential of indigenous fungal strains, specific to a region, could play a critical role in the continuous search for novel strains with superior activities on a global scale. This research focused on the ethanolic (EtOH) and hot-water (H2O) extracts of fruiting bodies of two wild-growing Ganoderma species: G. pfeifferi and G. resinaceum with an aim to assess its nutritional (total carbohydrate content-TCC), and mineral composition in relation to bioactive properties: antioxidant, antiproliferative and lipid-lowering. Atomic absorption spectrophotometry (AAS) revealed that G. pfeifferi is a promising source of minerals that are essential for numerous physiological functions in the human body like bone health and muscle and nerve function, with calcium (Ca 4.55 ± 0.41 mg/g d.w.) and magnesium (Mg 1.33 ± 0.09 mg/g d.w.), being the most abundant macro element present. Zinc (Zn), manganese (Mn), and chromium (Cr) were particularly notable, with concentrations ranging from 21.49 to 41.70 mg/kg d.w. The EtOH extract of G. pfeifferi demonstrated significantly elevated levels of TCC, essential macromolecules for energy and structural functions in the body, with higher quantities of all three standard carbohydrates detected in this type of extract. Similar to revealed composition the same species, G. pfeifferi stood out as the most prominent antioxidant agent, with H2O extract being stronger than EtOH in ABTS assay (86.85 ± 0.67 mg TE/g d.w.), while EtOH extract displayed the highest anti OH• radical scavenging ability (IC50 = 0.18 ± 0.05 μg/mL) as well as the most notable reducing potential among all. The highest antiproliferative effect against the breast cancer cell line (MCF-7), demonstrated the H2O extracts from G. resinaceum with the most pronounced activity after 24 hours (IC50 = 4.88 ± 0.50 μg/mL) which surpasses that of the standard compound, ellagic acid (IC50 = 33.94 ± 3.69 μg/mL). Administration of both Ganoderma extracts mitigated diabetic lipid disturbances and exhibited potential renal and hepatic protection in vivo on white Wistar rats by preservation of kidney function parameters in G. resinaceum H2O pre-treatment (urea: 6.27 ± 0.64 mmol/L, creatinine: 50.00 ± 6.45 mmol/L) and the reduction of ALT levels (17.83 ± 3.25 U/L) com-pared to diabetic control groups treated with saline (urea: 46.98 ± 6.01 mmol/L, creatinine: 289.25 ± 73.87 mmol/L, and ALT: 60.17 ± 9.64 U/L). These results suggest that pre-treatment with G. resinaceum H2O extracts may have potential antidiabetic properties. In summary, detected microelements are vital for maintaining overall health, supporting metabolic processes, and protecting against various chronic diseases. Further research and dietary assessments could help determine the full potential and applications of two underexplored Ganoderma species native to Serbia in nutrition and health supplements.

(1) Background: Although multiple studies have reported on the therapeutic effects of Atezo+Bev for the treatment of NASH-related liver cancer, few studies have focused on its effect on liver reserve. Here, we aimed to compare the changes in hepatic reserve during the Atezo+Bev treatment of NAFLD/NASH-related HCC and of non-NAFLD/non-NASH-related HCC. (2) Methods: We retrospectively compared the changes in ALBI score in 109 patients with NAFLD/NASH or non-NAFLD/non-NASH during 12 weeks of treatment with Atezo+Bev for advanced HCC between September 2019 and January 2022. PSM was performed, and the OS, PFS, and PPS of the two groups were compared. (3)Results: The ALBI after 12 weeks of Atezo+Bev treatment was significantly worse in the NAFLD/NASH group than in the non-NAFLD/non-NASH group. Analysis of the 24 propensity score-matched pairs of cases with NAFLD/NASH or non-NAFLD non-NASH yielded similar results. The prognoses of the two groups were similar with respect to OS and PFS, but the NAFLD/NASH group had a significantly shorter PPS. The 24 matched pairs had similar OS and PFS, but the PPS of the NAFLD/NASH group was shorter. (4)Conclusion: Atezo+Bev treatment may worsen hepatic reserve, and there-fore life expectancy, in patients with NAFLD/NASH-related liver cancer.

Although many policosanols from different sources, such as sugar cane, rice bran, and insects, have been marketed worldwide, there has been no comparative study of the in vivo efficacy using a hyperlipidemic animal model. This study compared the efficacy of treating dyslipidemia with four different policosanols, including one sugar cane wax alcohol from Cuba (Raydel®) and three policosanols from China (Xi’an Natural sugar cane, Xi’an Realin sugar cane, and Shaanxi rice bran) in hyperlipidemic zebrafish. After 12 weeks of consumption of each policosanol (final 0.1% in diet, wt/wt) and high cholesterol diet (HCD, final 4%, wt/wt) in a tetrabit, the Raydel policosanol group and Xi’an Natural policosanol group showed the highest survivability of approximately 81%, whereas the Xi’an Realin policosanol group and Shaanxi policosanol group showed 57% and 67% survivability, respectively. Among five HCD groups, the Raydel policosanol group showed the lowest serum total cholesterol (TC, p<0.001 versus HCD control) and triglyceride (TG, p<0.001 versus HCD control) with the highest percentage of high-density lipoproteins (HDL)-C in TC. The Raydel policosanol group also showed the lowest serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels with the least infiltration of inflammatory cells and interleukin-6 production in hepatocytes. In the ovary, the Raydel policosanol group also showed the highest contents of mature vitellogenic oocytes with the lowest production of reactive oxygen species and cellular apoptosis in ovarian cells. In the testis, the Raydel policosanol group also showed the healthiest morphology for spermatogenesis with the least interstitial area and reactive oxygen species (ROS) production in testicular cells. In conclusion, 12 weeks of Raydel policosanol consumption resulted in remarkable improvement of the blood lipid profile, amelioration of inflammation in the liver, and enhancement of the cell morphology in the ovary and testis with the highest survivability under the HCD.

In a search for a reliable, inexpensive, and versatile technique for high-throughput kinetic assays of drug metabolism, we elected to rehire an old-school approach based on the determination of formaldehyde (FA) formed in cytochrome P450-dependent demethylation reactions. After evaluating several fluorometric techniques of FA detection, we choose the method based on the Hantzsch reaction with acetoacetanilide as the most sensitive, robust, and adaptable to high-throughput implementation. Here we provide a detailed protocol for the use of our new technique for automatized assays of cytochrome P450-dependent drug demethylations and discuss its applicability for high-throughput scanning of the pathways of drug metabolism in the human liver. To probe our method further, we applied it to re-evaluating the pathways of metabolism of ketamine, a dissociative anesthetic, and potent antidepressant increasingly used in the treatment of alcohol withdrawal syndrome. Probing the kinetic parameters of ketamine demethylation by 11 major cytochrome P450 (CYP) enzymes, we demonstrate that besides CYP2B6 and CYP3A enzymes, which were initially recognized as the primary metabolizers of ketamine, an important role is also played by CYP2C19, and CYP2D6, while the involvement of CYP2C9 suggested in the previous reports deemed insignificant.

Abstract: Nonalcoholic fatty liver disease, characterized by the lipid accumulation within hepatocytes exceeding 5% of liver weight, is strictly related to metabolic disorders and to obesity and diabetes and represents a health emergency worldwide. Being not available any standard therapy for NAFLD, a key role is ascribed to lifestyle intervention including phytonutrient intake to prevent NAFLD development and progression. We have used a rat model of NAFLD to evaluate the effect of dietary supplementation with red tomato and golden tomato, patented mix of fruit with different degrees of ripeness, particularly rich in naringenin and chlorogenic acid, after steatosis development. We have assessed the ef-fects on body weight, metabolic profile, and hepatic steatosis and a correlation between the amelioration of all the parameters and the liver gene expression was evidenced. We found that the genes mainly up regulated by tomatoes administration were HNF4, Lepr and GK, able to condition metabolic homeostasis. Our results suggest that there is a role for red and golden tomatoes, dietary intake as a nutraceutical approach of NAFLD prevention and therapy.

The clinical characterization of small hepatocellular carcinoma (HCC) lesions in the liver and differentiation from heterogeneous inflammatory or fibrotic background is important for early detection and treatment. Metabolic monitoring of hyperpolarized ¹³C-labeled substrates has been suggested as a new avenue for diagnostic magnetic resonance. The metabolism of hyperpolarized [1-¹³C]pyruvate was monitored in mouse precision-cut liver slices (PCLS) of aged MDR2-KO mice, which served as a model for heterogeneous liver and HCC that develops similarly to the human disease. The relative in-cell activities of lactate dehydrogenase (LDH) to alanine transaminase (ALT) were found to be 0.40 ± 0.06 (n = 3) in healthy livers (from healthy mice), 0.90 ± 0.27 (n = 3) in heterogeneously inflamed liver, and 1.84 ± 0.46 (n = 3) in HCC. Thus, the in-cell LDH/ALT activities ratio was found to correlate with the progression of the disease. The results suggest that the LDH/ALT activities ratio may be useful in the assessment of liver disease. Because the technology used here is translational to both small liver samples that may be obtained from image-guided biopsy (i.e., ex vivo investigation) and to the intact liver (i.e., in a non-invasive MRI scan), these results may provide a path for differentiating heterogeneous liver from HCC in human subjects.

The fixed offshore platforms in Mexico produce approximately 1.90 million barrels of oil daily, valued at about 1.5 million dollars, positioning Mexico as a significant oil-producing nation globally. Ensuring the structural integrity of these platforms is highly complex due to various factors, including operational loads, meteorological conditions, extreme storms, seismic activity, and fatigue in tubular joints. Consequently, in situ studies have been conducted, focusing on operational analysis, static storm conditions, dynamic seismic strength, ductility, ultimate wave resistance, and spectral fatigue analysis. These six analyses (three linear, two nonlinear, and one spectral fatigue) provide insights into the structural behavior under different loading conditions and allow evaluation against current standards to conclude their structural integrity. The results obtained confirm that the structural integrity is adequate, as they meet current regulations and standards.

In developing his cosmological model of 1917, de Sitter theoretically predicted the phenomenon of cosmological redshift (the de Sitter effect), which he did long before the discovery of this phenomenon in observations. The de Sitter effect is gravitational by its nature, as it is due to differences between the coordinate systems of the observer and the distant source. However, the relationship between the redshift and distance derived from the de Sitter metric is at odds with observations, since this relationship is nonlinear (quadratic) for small redshifts, while the observed relationship between the same quantities is strictly linear. This paper discusses the possibility that cosmological redshift is gravitational by its nature, as in de Sitter’s 1917 model. At the same time, here, as in de Sitter’s model, an elliptical space is used, the main characteristic of which is the identification of its antipodal points. But, unlike de Sitter’s model, here, in order to ensure a strict linear dependence of the redshift on distance, the origin of the reference system is transferred to the observer’s antipodal point. The Schwarzschild-de Sitter metric used in this model allows you to estimate the curvature of space from observational data. To do this, a theoretical Hubble diagram is built within the framework of the model with the Schwarzschild-de Sitter metric, which is compared with observations from the Pantheon+ catalogue of type Ia supernovae and the Amati catalogue of gamma-ray bursts in the redshift range of 0&lt;z&lt;8. As a results of the comparison, the lower estimate of the radius of curvature of space turned out to be quite large: 2.3·1015 Mpc. This means that the observational data indicate a negligible curvature of space.

On the H-type group G⊂Rm×Rn, we study the existence of solutions for the Brezis-Nirenberg problem

This study investigates the effects of subclinical hypothyroidism and BDNF on telomere length in T1DM mothers and their neonates. Methods: In this prospective cohort study, 70 pregnant women with T1DM were enrolled. Subclinical hypothyroidism during the first trimester was characterized by elevated thyroid-stimulating hormone (TSH) levels ranging from 2.5 to 5.0mIU/L alongside normal free thyroxine (FT4) concentrations. Participants were stratified into two groups based on TSH levels: a maternal subclinical hypothyroid group (SHG, n=35) and a maternal euthyroid group (ETG, n=35). Leukocyte telomere length (LTL) measurements were conducted using whole blood samples from the mothers and umbilical veins. Results: The maternal LTL mean was 1.7 (SD=1.1), which was significantly shorter than the neonatal telomeres, with a mean of 2.3 SD (1.2). A significant correlation was observed between maternal and neonatal LTL (r=0.750, p&lt;0.001). A positive association was found between neonatal LTL and BDNF levels in maternal circulation [β=0.421 (95% CI 0.536; 1.873; p=0.001)]. Neonatal LTL was negatively associated with gestational weight gain [β=-0.266 (95% CI-0.138; -0.009)], and with TSH in the first trimester [β=-0.237; (95% CI -0.493; - 0.010)]. Notably, neonates in the SHG exhibited shorter LTL, with a mean of 2.1 (1.0), compared to those in the ETG, who had a mean LTL of 2.7 (1.4). A positive association was found between maternal LTL and BDNF levels in maternal circulation [β=0.523 (95% CI 0.790; 1.950; P&lt;0.001)]. Maternal LTL was negatively associated with gestational weight gain [β=-0.259 (95% CI -0.122; -0.010)], and with TSH in the first trimester [β=-0.231; (95% CI -0.422; - 0.015)]. Conclusions: Genetic factors affect neonatal LTL. Maternal subclinical hypothyroidism reduces neonatal LTL. The link between maternal and neonatal LTL and BDNF reveals the complex endocrine-neurotrophic interaction in T1DM telomere dynamics.

Dietary fibers regulate intestinal barrier function; however, the precise mechanisms remain unclear. This study investigated the effects of psyllium fibers on antimicrobial protein expression, focusing on the type II immunity and tuft cell-group 2 innate lymphoid cell (ILC2) circuit in the small intestine of the mouse. Supplemental psyllium fiber upregulated antimicrobial proteins, such as small proline-rich protein 2A (SPRR2A) and resistin-like beta (RELMβ), in mouse small intestine, evidently affecting cecal microbiota composition. Psyllium fibers also increased the RNA and protein expression of molecules related to ILC2 and tuft cells, such as IL-13, IL-25, DCLK1, Gfi-1b, SH2 domain-containing protein 3C, and Spi-B. In addition, ILC2 inhibitor (disulfiram) and bitter taste receptor blocker administration reduced psyllium-induced SPRR2A and RELMβ expression. Collectively, psyllium supplementation upregulates antimicrobial proteins such as SPRR2A and RELMß via the type II immune response and tuft cell-ILC2 circuit in the mouse small intestine.

Let a,b,c be positive integers such that a²+b²=c², 2|b,gcd(a,b)=1. In 1956, Jesmanowicz conjectured that for any positive integer w, the only solution of (aw)^x+(bw)^y=(cw)^z in positive integers is (x, y, z) = (2, 2, 2). In this paper, based on Gaussian integer ring, we show that Je$\acute{s}$manowicz' conjecture is true for any positive integer

Existing research indicates that mineralization of Carlin-type gold deposit is related to geological structures, but current studies mostly focus on the qualitative association, and lack quantitative analysis of the relationship between mineralization and structural features, which limits the potential for predictive mineral exploration. In this study, the Nibao Carlin-type gold deposit was selected as the research area to conduct three-dimensional geological modeling, spatial analysis, and three-dimensional prospectivity modeling. Spatial analysis revealed that the majority of gold ore bodies are situated near the main fault, with gold mineralization primarily occurring within a spatial range of approximately -80 meters to 20 meters from the main fault plane. This spatial distribution predominantly aligns in a SW-NE direction. Spatial characteristic extraction of fault slope indicators suggests that the slope angles are conducive to the migration and accumulation of ore-forming hydrothermal fluids, with ore body metal content rapidly increasing within an angle range of approximately 20° to 60°. The shape analysis of the mainfault indicates that the principal spaces of mineralization enrichment are within -10m to 20m of the fault plane undulations, where gold resources are concentrated in a relatively flat area. However, the degree of mineralization is more pronounced in the protruding sections than in the depressed areas. The areas with significant dip changes in faults display higher variations in orebody attitudes, with mineralization noticeably weaker in areas where the fault steepness changes markedly. Ore-bearing units exhibit significantly higher grades within the -17° to 3° interval of fault steepness transition. This interval also sees a rapid accumulation of gold resources. The Nibao gold mine's mineralization is derived from deep, ore-bearing hydrothermal fluids ascending along major fractures, precipitating, and accumulating in favorable ore-hosting spaces (faults, anticline cores) and lithological combinations (sedimentary tuffs, tuffs). Three deep potential gold targets were identified, highlighting the deep western edge of the F1 fault and the deep southeast-trending lower plate as prospective areas for future exploration. This study underscores the effectiveness of 3D prospective modeling as an indispensable tool for elucidating the spatial distribution of fault-controlled Carlin-type gold deposits and their tectonic determinants.

It is essential to have a thorough knowledge of the genetic variation among different strains of Xanthomonas citri pv. citri (Xcc), which is responsible for causing citrus bacterial canker. This understanding is important for studying the disease’s characteristics, population structure, and evolution, and ultimately for developing sustainable methods of control. A total of 48 strains, obtained from citrus production areas in Burkina Faso in 2012, 2020, and 2021, were subjected to polymerase chain reaction (PCR) tests using specific primers. The aim was to examine the distribution of type 3 effectors (T3E) and determine the geographical origins of the strains. The examination of the distribution of type 3 non-transcription activate like effectors (TALE) indicates a broader range in strains obtained in 2020 and 2021 compared to those obtained in 2012. However, all strains possess a shared set of three genes, specifically XopE2, XopN, and AvrBs2. Furthermore, all examined effectors were observed in the Bobo-Dioulasso region. Regarding the characterization of TALEs, two profiles containing two to three TALEs were discovered. Profile 1, consisting of two TALEs, was found in 37 Xcc strains, whereas Profile 2, comprising three TALEs, was detected in 11 strains. Out of the three TALEs (A, B, and C) that were identified, TALEs B and C were present in all strains. The correlation matrix indicated a positive association between the T3E content of strains and the duration of their isolation. Principal component analysis revealed a limited organization of the strains under investigation

A comprehensive understanding of the genetic diversity among strains of Xanthomonas citri pv. citri (Xcc), the causative agent of citrus bacterial canker, is crucial for unraveling the pathological nature, structure, and evolution of populations, thereby facilitating the adoption of sustainable control measures. In a collection of 48 strains isolated in 2012, 2020, and 2021 from citrus production areas in Burkina Faso, polymerase chain reaction (PCR) tests utilizing specific primers were conducted to investigate the distribution of type 3 effectors (T3E) and the structuring of strains based on their geographical origins. The analysis of the distribution of type 3 non-transcription activate like effectors (TALE) reveals a more extensive repertoire in strains isolated in 2020 and 2021 compared to those isolated in 2012. Nevertheless, all strains share a common repertoire of three genes, namely XopE2, XopN, and AvrBs2. Additionally, all screened effectors were observed in the Bobo-Dioulasso locality. Concerning the characterization of TALEs, two profiles consisting of two to three TALEs were identified. Profile 1, with two TALEs, was present in 37 Xcc strains, while Profile 2, with three TALEs, was identified in 11 strains. Among the three TALEs (A, B, and C) identified, TALEs B and C were common to all strains. The correlation matrix revealed a positive correlation between the T3E content of strains and the years of their isolation. Multiple component analysis indicated a weak structuring of the tested strains.

The late diagnosis of Type 2 Diabetes Mellitus can occur due to lack of access to the primary health care system and the non-manifestation of symptoms. Faced with this problem, this work presents the creation of a mobile application, called DiabetesCheck, for predicting the risk of Type 2 Diabetes Mellitus. A mathematical model is used, which classifies the risk of Type 2 Diabetes Mellitus for a group of patients with intervention and for a comparative group, using Fuzzy Classification and Decision Trees. The proposed application allows the health professional to monitor patients through the history stored in a database, allowing a representation of the evolution of patients and indication of medications. Therefore, this proposal aims to carry out the diagnosis in the initial phase of the disease and help in the prescription of more effective treatments and in the proposition of public policy strategies in epidemiology and screening.

The structural, elastic, and electronic properties of orthorhombic Cd2SiO4 and Hg2GeO4 were examined under varying pressure conditions using first-principles calculations based on densi-ty-functional theory employing the projector augmented wave method. The obtained cell pa-rameters at 0 GPa were found to align well with existing experimental data. We delved into the pressure-dependence of normalized lattice parameters and elastic constants. In Cd2SiO4, all lat-tice constants decreased as pressure increased, whereas in Hg2GeO4, parameters a and b de-creased while parameter c increased under pressure. Employing the Hill average method, we calculated the elastic moduli and Poisson’s ratio up to 10 GPa, noting an increase with pressure. Evaluation of ductility/brittleness under pressure indicated both compounds remained ductile throughout. We also estimated elastic anisotropy and Debye temperature under varying pres-sures. Cd2SiO4 and Hg2GeO4 were identified as indirect band gap insulators, with estimated band gaps of 3.34 eV and 2.09 eV, respectively. Interestingly, Cd2SiO4 exhibited a significant increase in band gap with increasing pressure, whereas the band gap of Hg2GeO4 decreased under pres-sure, revealing distinct structural and electronic responses despite their similar structures.

In this paper, we study the constrained minimization problem for an energy functional which is related to the following Kirchhoff type equation \begin{equation*} -\Big(\eta+b\big(\int_{\R^{3}}|\nabla u|^{2}dx\big)^{s}\Big)\Delta u+V(x)u=\mu u +\lambda|u|^{p}u,\end{equation*} where $b$ is a positive constant, parameters $\eta\geq0, \lambda>0$, exponents $s>0$, $0

Background: The aim was to diagnose Candida in the oral cavity of subjects with type 2 diabetes mellitus (T2DM) using a genotyping technique and to compare the results with those from con-ventional diagnosis by Papanicolau (Pap) staining. Methods: Palatal mucosa smears were per-formed in 18 dental care patients diagnosed with T2DM and grade I, II, and III prosthetic stomatitis who met the inclusion criteria; 18 healthy control subjects were also included in the study. He-moglobin A1c (HbA1c) levels were determined from total blood. Using exfoliative cytology, the Pap staining technique was used to diagnose candidiasis. Exfoliative cytology was also used for molecular diagnosis; DNA was obtained for Candida genotyping and RNA was used for gene ex-pression studies. Results: Clinical patterns indicated that all subjects were positive for Candida; however, Pap analysis revealed only three positive subjects, whereas end-point polymerase chain reaction (PCR) analysis revealed fifteen subjects with some type of Candida. The most common Candida species found were Candida guilliermondii (38.8%), Candida krusei (33.3%), Candida tropicalis, and Candida lusitaniae (22.2%). Interestingly, the coexpression of different species of Candida was found in various patients. In all patients, HbA1c levels were increased. Gene expression analysis showed a significant decrease (p ≤ 0.05) in TLR2 expression in positive subjects, whereas TLR4 expression did not differ significantly among patients. Conclusions: The end-point PCR technique showed better sensitivity for diagnosis of Candida when compared with diagnosis by Pap staining. T2DM subjects showed an increased presence of C. guilliermondii that was correlated with decreased TLR2 expression

Milroy's disease (MD), also known as hereditary lymphedema type I, is a rare autosomal dominantly inherited primary lymphedema. It accounts for approximately twenty percent of all primary lymphedemas. MD typically presents clinically with bilateral lower extremity lymphedema. Our case report is about a rare case of MD presenting with unilateral lymphedema in both upper and lower extremities in a patient admitted to our clinic. A 24-year-old woman who had been under observation for lymphedema since she was 8 years old was diagnosed with MD by physical examination, venous Doppler ultrasound, whole body lymphoscintigraphy, and molecular genetic testing in our clinic, and partial improvement was achieved with Complete Decongestive Therapy, the gold standard treatment for lymphedema. Genetic counseling services may be especially useful for the patient and family. Although MD is rarely seen in the literature, many more studies are needed to identify carrier variants in the community.

Background. Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in poorer nations. The high prevalence of obesity and the ensuing diabetes is attributed to rapid economic progress, physical inactivity, consumption of high-calorie foods, and changing lifestyles. Objectives. We investigated the role of pro-inflammatory chemokines; CCL1, 2, 4 and 5 with varying levels of obesity in T2DM in the Asir region of Saudi Arabia. Materials and methods. 170 confirmed T2DM patients and a normal control group were enrolled. The demographic data, serum levels CCL-1, 2, 4 and 5 and the biochemical indices were assessed in patients and control groups by standard procedures. Results. T2DM patients were divided into four groups: A (normal body weight), B (Overweight), C (obese), and D (highly obese). n controls. We observed that male and female control patients had similar mean serum concentrations of pro-inflammatory chemokines CCL 1, 2, 4, and 5. Chemokines CCL1, CCL2, and CCL4 in the serum of Type 2 Diabetes Mellitus patients with normal or overweight body weights were significantly higher than the control group, regardless of gender. In T2DM individuals with obesity and severe obesity, the rise was most significant. There was a progressive rise in the concentrations of CCL1, 2, and 4 in T2DM) patients with increasing BMI. Serum CCL5 levels increased significantly in all T2DM patient groups. The increase in CCL5 was more predominant in normal-weight people as compared to overweight and obese T2DM patients. Conclusions. Male and female control patients had similar serum levels of pro-inflammatory chemokines CCL 1, 2, 4, and 5. The progressive rise in blood concentrations of three Pro-inflammatory chemokines; CCL1, 2, and 4 in T2DM patients with increasing BMI supports the idea that dyslipidemia and obesity contribute to chronic inflammation and insulin resistance. Serum CCL5 levels increased significantly in all T2DM patient groups. The selective and more pronounced increase of CCL5 in the T2DM group with normal BMI as compared to patients with varying degrees of obesity, was rather surprising. Further research is needed to determine if CCL5 under-expression in overweight and obese T2DM patients is due to some unexplained counterbalancing processes.

In this paper, we study a differential operator of parabolic type with a variable and unbounded coefficient, defined on an infinite strip. Sufficient conditions for the existence and compactness of the resolvent are established, and an estimate for the maximum regularity of solutions of the equation Lu=f∈L_2(Ω) is obtained. Two-sided estimates for the distribution function of approximation numbers are obtained. As is known, estimates of approximation numbers show the rate of best approximation of the resolvent of an operator by finite-dimensional operators. The paper proves the assertion about the existence of positive eigenvalues among the eigenvalues of the given operator and finds two-sided estimates for them.

Type 2 diabetes mellitus (T2DM) is a common metabolic disease characterised by insulin resistance and elevated blood glucose levels, affecting millions of people worldwide. T2DM patients with dyslipidaemia have an increased risk of cardiovascular disease (CVD). A complex interplay of risk factors such as hyperglycaemia, dyslipidaemia, hypertension, obesity, inflammation and oxidative stress favour the development of atherosclerosis, a central mechanism in the pathogenesis of cardiovascular disease. Dyslipidaemia, a hallmark of T2DM, is characterised by elevated triglycerides, decreased high-density lipoprotein (HDL) cholesterol and the presence of small, dense low-density lipoprotein (LDL) particles, all of which promote atherosclerosis. In this article, we have attempted to present various treatment strategies that include pharmacological interventions such as statins, ezetimibe, PCSK9 inhibitors, fibrates and omega-3 fatty acids. We have also tried to highlight the pivotal role of lifestyle modifications, including physical activity and dietary changes, in improving lipid profiles and overall cardiovascular health in T2DM patients. We have also tried to present the latest clinical guidelines for the management of dyslipidaemia in T2DM patients. In conclusion, the treatment of dyslipidaemia in T2DM patients is of great importance as it lowers lipid particle levels, slows the progression of atherosclerosis and ultimately reduces susceptibility to cardiovascular disease.

Type 1 diabetes imposes a complex and challenging routine on patients and caregivers. Therefore, considering individual experiences and personal facilitators to promote assertive interventions is crucial. However, no studies have addressed these perspectives in the Brazilian adult population. We aimed to identify psycho-behavioral characteristics perceived as facilitators for coping with the condition. We used a biographical method to conduct semi-structured, face-to-face, in-depth interviews for each participant. Transcripts were analyzed using inductive thematic analysis. Participants (n = 22) were aged 18–57 years (mean: 30.2, standard deviation (SD): 8.7), and the duration since diagnosis was approximately 20.6 years (SD: 4.6). Twelve (54.4%) were women, 13 (59.1%) used insulin pumps, 14 (63.6%) had at least a college degree, and 13 (59.1%) had HbA1C (glycated hemoglobin) levels above 58 mmol/mol (7.5%). Five major themes emerged: 1) peer learning, 2) ownership, 3) welcoming experiences, 4) equity, and 5) reframe the path (P.O.W.E.R.). All themes appeared in the lived experiences shared by participants with HbA1C levels below 58 mmol/mol (7.5%). Improved glycemic control can be achieved, and the challenges encountered in diabetes care within similar socioeconomic contexts can be addressed, by an interdisciplinary care team that takes P.O.W.E.R into consideration when providing person-centered care strategies.

The microwave field is used for drying and disinfection of grain, during pre-sowing seed treat-ment. The use of a microwave field in these installations leads to an increase in their productivity and a decrease in the energy consumed by them. One of the principal problems of microwave field use for treatment of dense grain layers is to insure sufficient distribution uniformity of the field. In this article, waveguide design options have been discussed that serve to introduce microwave radiation into the grain layer. Mathematical simulation of the electromagnetic field distribution was performed with the use of CST Microwave Studio software in order to evaluate and compare horn-type, rectangular and semicircular waveguides. The data on the standing wave ratio and radiation efficiency for these types of waveguides have been reported. Specific features of the microwave electromagnetic field distribution and radiation power in the output of those wave-guides have been described. Results of mathematical simulations enabled to make out that sem-icircular waveguides with slot-type radiators are preferable for processing dense grain layers.

Adipose tissue is a crucial organ in energy metabolism and thermoregulation. Adipose tissue phenotype is controlled by various signaling mechanisms under pathophysiological conditions. Type II transmembrane serine proteases (TTSPs) are a group of trypsin-like enzymes anchoring on the cell surface. These proteases act in diverse tissues to regulate physiological processes, such as food digestion, salt-water balance, iron metabolism, epithelial integrity, and auditory nerve development. More recently, several members of the TTSP family, namely, hepsin, matriptase-2, and corin, have been shown to play a role in regulating lipid metabolism, adipose tissue phenotype, and thermogenesis, via direct growth factor activation or indirect hormonal mechanisms. In mice, hepsin deficiency increases adipose browning and protects from high-fat diet-induced hyperglycemia, hyperlipidemia, and obesity. Similarly, matriptase-2 deficiency increases fat lipolysis and reduces obesity and hepatic steatosis in high-fat diet-fed mice. In contrast, corin deficiency increases white adipose weights and cell sizes, suppresses adipocyte browning and thermogenic responses, and causes cold intolerance in mice. These findings highlight an important role of TTSPs in modifying cellular phenotype and function in adipose tissue. In this review, we provide a brief description about TTSPs and discuss recent findings regarding the role of hepsin, matriptase-2, and corin in regulating adipose tissue phenotype, energy metabolism, and thermogenic responses.

Background: The global prevalence of anxiety and depressive symptoms in adolescents has increased considerably during the COVID-19 pandemic. Mental health problems may compromise glycemic control in young people with type 1 diabetes; however, evidence of improved glycemic control in adolescents with T1D appeared early during the pandemic. This qualitative study aimed to provide a more in-depth understanding of how the COVID-19 pandemic affected adolescents with type 1 diabetes routines, experiences, T1D management, behaviors, and mental health. Methods: 24 adolescents, aged 15-18 years, with DM1, joined the discussion of focus groups in the context of the summer camp for diabetes. Word frequency and thematic analysis were conducted on adolescents’ narratives. Results: The word Frequency Analysis identified 'friends', 'family', and 'home' as the most frequent terms. Seven themes were identified: (1) COVID-19 and T1D; (2) emotional reactions to the COVID-19 pandemic; (3) changes in daily life; (4) feelings of loss; (5) coping with the COVID-19 pandemic; (6) the COVID-19 pandemic as an opportunity; (7) return to (new) normality. Conclusions The COVID-19 pandemic may have represented a more stressful condition for adolescents with DM1, facing additional challenges compared to their healthy peers. The results offer directions to the diabetes care team for a customized intervention while the consequences of the pandemic on adolescents’ health continue.

Recurrent hypoglycaemia, a common side-effect of insulin therapy in the treatment of type 1 diabetes, induces impaired glucose-sensing. Better understanding of how astrocytes, important non-neuronal cells in the brain, function in low glucose environments may improve our understanding of recurrent hypoglycaemia-induced defective counterregulation. Astrocytes contribute to glutamatergic signalling, which is required for hypoglycaemia counterregulation and is impaired by recurrent insulin-induced hypoglcyaemia. This study examined the glutamate response of astrocytes when challenged with acute and recurrent low glucose (RLG) exposure. The metabolic responses of cortical (CRTAS) and hypothalamic (HTAS) primary rat astrocytes were measured in acute and recurrent low glucose using extracellular flux analyses. RLG caused mitochondrial adaptations in both HTAS and CRTAS, many of which were attenuated by glutamate exposure during low glucose treatments. We observed an increase in capacity of HTAS to metabolise glutamine after RLG exposure. Demonstrating astrocytic heterogeneity in the response to LG, CRTAS increased cellular acidification, a marker of glycolysis in LG, whereas this decreased in HTAS. The directional change in intracellular Ca2+ levels of each cell type, correlated with the change in extracellular acidification rate (ECAR) during LG. Further examination of glutamate-induced Ca2+ responses in low glucose treated CRTAS and HTAS identified sub-populations of glucose-excited- and glucose-inhibited-like cells with differing responses to glutamate. Lastly, release of the gliotransmitter ATP by HTAS was elevated by RLG, both with and without concurrent glutamate exposure. Therefore, hypothalamic astrocytes adapt to RLG by increasing glutamate uptake and oxidation in a manner that attenuates RLG-induced mitochondrial adaptations.

Mesenchymal stem cells (MSCs) are involved in the process of extracellular matrix (ECM) remodeling where collagens play a pivotal role. We recently demonstrated that the remodeling of adsorbed collagen type I might be disordered upon oxidation following its fate in the presence of human adipose-derived MSC (ADMSCs). With the present study, we intended to learn more about the effect of polyphenolic antioxidant Epigallocatechin gallate (EGCG) attempting to mimic the conditions of oxidative stress in vivo and its putative prevention by antioxidants. Collagen Type I was isolated from mouse tail tendon (MTC) and labeled with FITC before oxidizing according to Fe2+/H2O2 protocol. FITC-collagen remodeling by ADMSC was assessed morphologically before and after EGCG pretreatment and confirmed via detailed morphometry analysis measuring the anisotropy index (AI) and fluorescence intensity (FI) in selected regions of interest (ROI), namely: outside the cells; over the cells and central (nuclear perinuclear) region, whereas the pericellular proteolytic activity was measured by de-quenching of fluorescent collagen probes (FRET effect). Here we provide morphological evidence that MTC undergoes significant reorganization by the adhering ADMSC along with the substantial activation of pericellular proteolysis, and further confirm that both processes are suppressed upon collagen oxidation. An important observation was that this abrogated remodeling cannot be prevented by the EGCG pretreatment. Conversely, the detailed morphometry analysis showed that oxidized FITC-collagen rather tends to accumulate beneath the cells and around the cell’s nuclei suggesting the activation of alternative routes for its removal, such as internalization and/or transcytosis. Morphometry analysis also revealed that both processes are supported by EGCG pretreatment.

We obtain exact solutions to the field equations for 5 dimensional LRS Bianchi type-I spacetime in $f(R,T)$ theory of gravity where specifically the following three cases are considered: (i) $f(R,T)=\mu(R+T)$, (ii) $f(R,T)=R \mu + R T \mu^2$ and (iii) $f(R,T)=R+\mu R^2+\mu T$ where $R$ and $T$ respectively the Ricci scalar and trace of the energy-momentum tensor. It is found that the equation of state (EOS) parameter $w$ is governed by the parameter $\mu$ involved in the $f(R,T)$ expressions. We fine-tune the parameter $\mu$ to obtain effect of phantom energy in the model, however we also restrict this parameter to obtain a stable model of the universe. It is noted that the model isotropizes at finite cosmic time.

In heterogeneous networks, the random walks based on meta-path requires prior knowledge and lacks flexibility. And the random walks based on non-meta-path only considers the number of node types, but does not consider the influence of schema and topology between node types in real networks. To solve the above problems, this paper proposes a novel model HNE-RWTIC (Heterogeneous Network Embedding Based on Random Walks of Type & Inner Constraint). Firstly, to realize the flexible walks, we design a Type strategy, which is the node type selection strategy based on the co-occurrence probability of node types. Secondly, to achieve the uniformity of node sampling, we design an Inner strategy, which is the node selection strategy based on the adjacency relationship between nodes. The Type & Inner strategy can realize the random walks based on meta-path, the flexibility of the walks, and can sample the node types and nodes uniformly in proportion. Thirdly, based on the above strategy, a transition probability model is constructed; then, we obtain the nodes embedding based on the random walks and Skip-Gram. Finally, in classification and clustering tasks, we conducted a thorough empirical evaluation of our method on three real heterogeneous networks. Experimental results shown that F1-Score and NMI of HNE-RWTIC outperform state-of-the-art approaches.

(1) Background: Deep hypothermic circulatory arrest (DHCA) with selective antegrade cerebral perfusion (ACP) is an established cerebral protection technique for the conduction of complex surgical procedures involving the aortic arch. It is controversial if the duration of DHCA is associated with adverse outcome in patients with acute type A aortic dissection (AAAD). Our goal was to investigate whether DHCA time was associated with surgical outcome in patients undergoing a surgical treatment of AAAD. (2) Methods: 410 Patients were divided into two groups concerning the DHCA time less than 60 minutes and equal or longer than 60 minutes. (3) Results: Patients with longer DHCA time were significantly younger (p=0.001). Intraoperatively, complex procedures with aortic arch surgery were more common in patients with longer DHCA time (p&lt;0.001). Accordingly, cardiopulmonary bypass (p&lt;0.001), cross-clamping (p&lt;0.001) and DHCA times (p&lt;0.001) were significantly longer in this group. Postoperatively, only the duration of mechanical ventilation (p&lt;0.001) and the rate of tracheotomy were significantly higher in these patients. 30-day mortality was satisfactory for both groups (p=0.746). (4) Conclusions: Our results showed that improvements in perioperative management including ACP allow a successful performance of surgical treatment of AAAD under DHCA with duration of even longer than 60 minutes.

Type 2 diabetes (T2D) is associated with increased cardiovascular morbidity, mortality, and hospital admissions. There is variability in clinical practice. The objectives are to analyze the variability in the control of Blood Pressure (BP), HbA1c, and LDL-C in T2D patients and its influence on admissions due to cardiovascular events (CVE) Methods: We analyzed the electronic records in Primary Care Health centers in Navarra (Spain) and hospital admission for CVE. We follow 480637 people from 2012 to 2016. We calculated indicators of control of patients with T2D for each year, percentage with: HbA1c &lt; 7%; HbA1c &gt;= 9%; BP &lt;140/90 mmHg; LDL-C &lt;100 mg/dl. We used logistic and Cox regression. Results: Patients in the best control GP practices cluster are 2.5 times more likely to have HbA1c &lt;7% [OR: 2.46 (95% CI: 2.29-3.64)]. Poor HbA1c control ≥ 9% is more likely in the worst control cluster [OR: 1.73 (95% CI:1.63-1.83)]. The probability of admission for CVE increases with age, being male, low income, obesity, history of CVE, having HbA1c ≥ 9%, and belonging to a GP practice in the cluster of HbA1C ≥ 9% worst control. In contrast, it decreases in patients with HbA1c &lt;7%, BP&lt;140/90 mmHg and LDL &lt;100 mg/dl.

A good management of diabetes requires at the same time self-regulation behaviour and a balanced involvement of family components. This study’s aims were: understanding fear of injections and perceptions of family conflicts in preadolescents and adolescents with type 1 diabetes mellitus and their mothers, comparing their perceptions, and identifying the risk factors impacting patients’ quality of life. Participants were one hundred and two patients (Mean age = 14.63, SD = 2.43; age range = 10-19 years; Females = 52) and their mothers (Mean age = 46.94, SD = 6.2, age range = 27-63 years), who filled in self and proxy-report questionnaires. Twenty % of patients and 14.7% of their mothers reported clinical score for fear of self-injection and blood testing. Mothers reported higher fear of injecting and family conflicts compared with the patients. Age, fear of injecting and family conflicts impacted significantly on patients’ quality of life perceptions. Clinical consideration and recommendations are given basing on the empirical results.

The influence of the hot isostatic pressing (HIP) post-processing step on structural and phase changes, porosity healing and mechanical strength in a powder metallurgy Ti35Nb2Sn alloy was studied. Powders were pressed at room temperature at 750 MPa, and then sintered at 1,350°C in a vacuum for 3 h. The standard HIP process at 1,200°C and 150 MPa for 3 h was performed to study its effect on a Ti35Nb2Sn powder metallurgy alloy. The influence of the HIP process and cold rate on density, microstructure, the quantity of interstitial elements, mechanical strength and Young's modulus was investigated. HIP post-processing for 2 h at 1,200°C and 150 MPa led to greater porosity reduction and a marked retention of the β phase at room temperature. The slow cooling rate during the HIP process affected phase stability, with a large amount of α”-phase precipitate, which decreased the titanium alloy’s yield strength.

Trichomes are a common morphological defense against pests, in particular, type IV glandular trichomes have been associated with resistance against different invertebrates. Cultivated tomatoes usually lack or have a very low density of type IV trichomes. Thus, specific breeding programs to incorporate these natural defences, that are common within the Solanum genus, might improve a more sustainable management. We have identified a S. pimpinellifolium accession with very high density of this type of trichomes. Two F2 mapping populations using two different parents have been developed, characterized and genotyped using a new genotype methodology, K-seq. We have been able to build an ultra-dense genetic map with 147,326 markers with an average distance between markers of 0.2 cM that has allowed us to perform a detailed mapping. We have used two different families and two different approaches, QTL mapping and QTL-seq, to identify several QTLs implicated in the control of trichome type IV developed in this accession on the chromosomes 5, 6, 9 and 11. The QTL located on chromosome 9 is a major QTL that has not been previously reported in S. pimpinellifolium that increases by a factor of 9 the density of trichomes.

Human activities for exploitation and utilization of coastal zones have transformed coastline morphology and severely changed regional flow fields, underwater topography, and sediment distribution in the sea. In this study, single-beam bathymetry coupled with sediment sampling and analysis was carried out to ascertain submarine topography, geomorphology and sediment distribution patterns and explore sediment provenance in Qinzhou Bay, China. The results show the following. 1) The underwater topography in Qinzhou Bay is complex and variable, with water depths in the range of 0–20 m. It can be divided into four underwater topographic zones: the central (outer Qinzhou Bay), eastern (Sanniang Bay), western (east of Fangcheng Port), and southern (outside of the bay) parts. 2) Based on geomorphological features, the study area comprises four major submarine geomorphological units (i.e., tide-dominated delta, tidal sand ridge group, tidal scour troughs, and underwater slope) and two intertidal geomorphological units (i.e., tidal flat and abrasion platforms). 3) Sandy sediments are widely present in Qinzhou Bay, accounting for 70% of the total sediments. From the mouth of the Maowei Sea to the offshore, the sediments gradually become coarser, shifting from sandy mud to muddy sand, and then to fine sand and medium–coarse sand. The detrital minerals contained in the sediments mainly consist of quartz, feldspar, debris, ilmenite, leucosphenite, and tourmaline, whereas the clay minerals are dominated by kaolinite, followed by illite and smectite. The sediment provenance is mainly terrigenous input from near-source rivers. With sea reclamation and dam construction, outer Qinzhou Bay has experienced enormous morphological variation of its coastline. Together with the channel effect where the velocity of ebb tide is greater than that of flood tide, the underwater topography is characterized by increased scale and height difference of troughs and ridges as well as enhanced offshore deposition.

Human activities for exploitation and utilization of coastal zones have transformed coastline morphology and severely changed regional flow fields, underwater topography, and sediment distribution in the sea. In this study, single-beam bathymetry coupled with sediment sampling and analysis was carried out to ascertain submarine topography, geomorphology and sediment distribution patterns and explore sediment provenance in Qinzhou Bay, China. The results show the following. 1) The underwater topography in Qinzhou Bay is complex and variable, with water depths in the range of 0–20 m. It can be divided into four underwater topographic zones: the central (outer Qinzhou Bay), eastern (Sanniang Bay), western (east of Fangcheng Port), and southern (outside of the bay) parts. 2) Based on geomorphological features, the study area comprises four major submarine geomorphological units (i.e., tide-dominated delta, tidal sand ridge group, tidal scour troughs, and underwater slope) and two intertidal geomorphological units (i.e., tidal flat and abrasion platforms). 3) Sandy sediments are widely present in Qinzhou Bay, accounting for 70% of the total sediments. From the mouth of the Maowei Sea to the offshore, the sediments gradually become coarser, shifting from sandy mud to muddy sand, and then to fine sand and medium–coarse sand. The detrital minerals contained in the sediments mainly consist of quartz, feldspar, debris, ilmenite, leucosphenite, and tourmaline, whereas the clay minerals are dominated by kaolinite, followed by illite and smectite. The sediment provenance is mainly terrigenous input from near-source rivers. With sea reclamation and dam construction, outer Qinzhou Bay has experienced enormous morphological variation of its coastline. Together with the channel effect where the velocity of ebb tide is greater than that of flood tide, the underwater topography is characterized by increased scale and height difference of troughs and ridges as well as enhanced offshore deposition.

Type 1 diabetes (T1D) is an autoimmune condition where the body’s immune cells destroy their insulin-producing pancreatic beta-cells leading to dysregulated glycaemia. Individuals with T1D control their blood glucose through exogenous insulin replacement therapy, often using multiple daily injections or pumps. However, failure to accurately mimic intrinsic glucose regulation results in glucose fluctuations and long-term complications impacting key organs such as the heart, kidneys, and/or the eyes. It is well-established that genetic and environmental factors contribute to the initiation and progression of type 1 diabetes, but recent studies show that epigenetic modifications are also important. Here, we discuss key epigenetic modifications associated with type 1 diabetes pathogenesis and discuss how recent research is finding ways to harness epigenetic mechanisms to prevent, reverse, or manage type 1 diabetes.

Anti-diabetic effects of Glycine soja seed extract (GS) on Type 2 diabetes mellitus mouse model and human hepatocytes induced insulin resistance were investigated. 3 weeks old db/db mice were divided into 5 groups (n = 6) including two control groups and 3 GS treated groups with different doses. Oral administration of GS for 6 weeks to diabetic db/db mice reduced blood glucose level significantly in a dose dependent manner by 44.7% (300 mg/kg/day), 30.9% (150 mg/kg/day) and 21.1% (75 mg/kg/day). GS treatment also lowered significantly plasma level of HbA1c, insulin, IGF-1 and leptin, and increased that of adiponectin. GS treatment activated AMPK, and down-regulated GLUT2 in liver tissues of mice while up-regulated GLUT4 in muscle tissues of mice. In in vitro study with insulin resistance induced human hepatocyte, GS treatment increased glucose uptake and increased the activities of Akt and PPAR-γ in response to insulin. Treatment of GS appears to reduce blood glucose level by regulating energy metabolism positively through various metabolic pathways and reducing insulin resistance in Type 2 diabetes mellitus.

Anti-diabetic effects of Glycine soja seed extract (GS) on Type 2 diabetes mellitus mouse model and human hepatocytes induced insulin resistance were investigated. 3 weeks old db/db mice were divided into 5 groups (n = 6) including two control groups and 3 GS treated groups with different doses. Oral administration of GS for 6 weeks to diabetic db/db mice reduced blood glucose level significantly in a dose dependent manner by 44.7% (300 mg/kg/day), 30.9% (150 mg/kg/day) and 21.1% (75 mg/kg/day). GS treatment also lowered significantly plasma level of HbA1c, insulin, IGF-1 and leptin, and increased that of adiponectin. GS treatment activated AMPK, and down-regulated GLUT2 in liver tissues of mice while up-regulated GLUT4 in muscle tissues of mice. In in vitro study with insulin resistance induced human hepatocyte, GS treatment increased glucose uptake and increased the activities of Akt and PPAR-γ in response to insulin. Treatment of GS appears to reduce blood glucose level by regulating energy metabolism positively through various metabolic pathways and reducing insulin resistance in Type 2 diabetes mellitus.

Indoor dusts are collectively formed from anthropogenic and atmospheric activities. Particle matter 10 (PM10) is inhalable and causes significant inflammation by interaction with the pulmonary epithelial barrier. The mediators involved in bronchial epithelial cells response to dust are remined unknown. The air-liquid interface of our lung on chip model was exposed to indoor dust collected from highly polluted houses in Delhi, India. The media were collected after 4 days and cytokine levels were measured. We found that the concentration of IFN, IFNγ, Interleukin-6 (IL-6), IL1b, TNFa, and Granulocyte monocyte colony stimulating factor (GM-CSF) were significantly increased after exposure to indoor dust. IFN type I pathways were a major response from dust exposure. Further investigation is needed to determine the mechanism of action and targets of dust in bronchial epithelial cells.

Late blight caused by the oomycete pathogen Phytophthora infestans is a devastating disease of potato and tomato worldwide, including Israel. The population structure of this pathogen was monitored in potato and tomato fields in Israel during a 36-year period of 1983-2019. Isolates of the pathogen were tested for sensitivity to phenylamide fungicides, mating type, race structure, and genotype. The phenotypic and genotypic structure of the population from potato have changed greatly from one year to another, from one season to the next, within a season and within a single field. Major changes also occurred in the population collected from tomato crops. The mechanisms driving these multiple changes and the heterogeneous nature of the population in Israel are shown to derive from multiple migration events of the pathogen via seed tubers from Europe and from fitness-driven selection processes.

In this paper we consider Changhee polynomials of type two, which are motivated from the recent work of Kim and Kim. We investigate some symmetry identities for the Changhee polynomials of type two which are derived from the properties of symmtery for the fermionic p-adic integral on Zp.

Single-particle tracking with quantum dots (QDs) constitutes a powerful tool to track the nanoscopic dynamics of individual cell membrane components unveiling their membrane diffusion characteristics. Here we tested the possibility of extracting from the nano-resolved (16 ms and 30 nm) population dynamics of several quantum dots, time-binned at the second time-scale, the rapid structural changes of the cell membrane surface. We used for this proof-of-concept study bright, small and stable biofunctional QD nanoconstructs recognizing the neuronal cannabinoid type 1 (CB1) receptor and a commercial point-localization microscope to reconstruct in 3D the dynamics of the plasma membrane surface of cultured cells with a spatial resolution of tens of nanometers. CB1 receptor was chosen because it’s a highly expressed and fast diffusing membrane protein. Therefore, rapid QD diffusion on the axonal plasma membrane of cultured hippocampal neurons allowed highly precise reconstruction of the membrane surface in less than one minute. QD nanoconstructs diffused into the membrane of synaptic clefts allowing the entire topological reconstruction of the presynaptic component. In addition, we demonstrated successful reconstruction of the remarkably high dynamics of membrane surface topology at the second time-scale both in HEK-293 cell filopodia and axons. Our results show that this novel technique, which we named nanoPaint, is a powerful precision tool for the study of the structural plasticity of cell membrane surfaces.

The generalization of Farey graphs and extended Farey graphs are all originated from Farey graph and scale-free and small-world simultaneously. We propose a labeling of the vertices for it that allows determining all the shortest paths routing between any two vertices only based on their labels. The maximum number of shortest paths between any two vertices is huge as the product of two Fibonacci numbers, however, the label-based routing algorithm runs in linear time O(n). The existence of an efficient routing protocol for Farey-type models should help the understanding of several physical dynamic processes on it.

In an open and dynamic IoT (the Internet of Things) environment, a common context information model is essential for active things to share common knowledge, reason their situations, and support adaptive interoperability with each other. There have been many studies on the IoT context information models based on semantic technology, but most of them have assumed a static situation based on a service-oriented information model suitable for specific applications of the IoT. In the case of applying their models to an open and dynamic IoT environment, two issues have been observed: Most of the models ignore (a) the mashup of the open-world semantics of context information generated by multiple context sources and (b) the reconciliation of the semantic relationships between multiple context entities under dynamic situation changes. Therefore, in this paper, we propose a context information model that is flexible enough to express complex and diverse semantic relationships between context information generated from a variety of context information sources in the IoT. The main background of this proposal is to propose an adaptive context model that can effectively mash up various context classes that use ontology in open and dynamic IoT environments. In this paper, we also show the effectiveness of the proposed model through an adequate verification model and a practical example.

Abstract Background: Diabetes mellitus is dramatically increasing in the wide world. The managing of diabetes care emphasized the self-management education and support into patients’ care and family care. Objective: to review and synthesizes the effectiveness of DSME strategies involving family as a key person to provide social support for diabetes mellitus self-management of glycemic uncontrolled patients Method: Three databases through PubMed, CINAHL, and Scopus were reviewed to assess the relevant articles. The following search terms: “type 2 diabetes,” “self-management,” “family support,” and “glycemic uncontrolled.” We summarized details of family support on self-management among glycemic uncontrolled patients for 14 existing studies. Results: A total of 22 intervention studies were identified. Those studies have a heterogeneous of the education strategies, support perceived, follow-ups strategies and outcomes among type 2 DM. Family integration on diabetes self-management education (DSME) has a positive impact on several outcomes including, self-care behaviors, psychological outcomes, self-efficacy and clinical outcomes Conclusions: This systematic review found robust data related to the integration of family support on diabetes self-management among glycemic uncontrolled patients. Consequently, the improvement in outcomes was identified. Implications: The findings suggest model of family engagement is better and needed for sustaining the diabetes care in the long-term care

This study investigated the effects of soil crust development on the underlying soil properties. The field sampling work was conducted in June 2016 in the Hobq Desert in Inner Mongolia, North China. Soil crust samples and 0–6, 6–12, 12–18, 18–24, 24–30 cm deep underlying soil samples were taken from five representative areas of different soil crust development stages. All samples were analyzed for physicochemical properties including water content, bulk density, aggregate content, organic matter content, enzyme activities, and microbial biomass carbon and nitrogen. The results showed that the thickness, water content, macroaggregate (>250 μm) content, organic matter content, microbial biomass and enzyme activities of the soil crusts gradually increased along the soil crust development gradient, while the bulk density of the soil crusts decreased. Meanwhile, the physicochemical and biological properties of the soils below the algal and moss crusts were significantly ameliorated when compared with the physical crust. Moreover, the amelioration effects were significant in the upper horizons (approx. 0–12 cm deep) and diminished quickly in the deeper soil layers.

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses metabolic dysfunction-associated fatty liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), with MASH posing a risk of progression to cirrhosis and hepatocellular carcinoma (HCC). The global prevalence of MASLD is estimated at approximately a quarter of the population, with significant healthcare costs and implications for liver transplantation. The pathogenesis of MASLD involves intrahepatic liver cells, extrahepatic components, and immunological aspects, particularly the involvement of macrophages. Hepatic macrophages are a crucial cellular component of the liver and play vital roles in liver function, contributing significantly to tissue homeostasis and swift responses during pathophysiological conditions. Recent advancements in technology have revealed the remarkable heterogeneity and plasticity of hepatic macrophage populations and their activation states in MASLD, challenging traditional classification methods like the M1/M2 paradigm and highlighting the coexistence of harmful and beneficial macrophage phenotypes that are dynamically regulated during MASLD progression. This complexity underscores the importance of considering macrophage heterogeneity in therapeutic targeting strategies, including their distinct ontogeny and functional phenotypes. This review provides an overview of macrophage involvement in MASLD progression, combining traditional paradigms with recent insights from single-cell analysis and spatial dynamics. It also addresses unresolved questions and potential therapeutic targets in this area.

Background and Aims: The impact of antibody response after direct-acting antiviral (DAA) therapy in hepatitis C virus (HCV)-infected recipients before and after liver transplantation (LT) is still undetermined. Methods: In this observational cohort study, we aimed to explore the association of changes in anti-HCV antibody titers after pre-LT DAA therapy with allograft injury, including biliary complications (BCs) and acute cellular rejection (ACR). Results: A total of 153 cases were enrolled from January 2015 to February 2021. Serum anti-HCV antibody titers were assessed before and after (day 30) LT. Among all recipients, 31/153 (20.3%) had pre-LT DAA therapy (DAA group) and 122/153 (79.7%) did not undergo pre-LT DAA therapy (DAA-naïve group). Higher incidence of post-LT BCs was observed in the DAA group (P = 0.028). Compared with the DAA-naïve group, the DAA group had a significantly higher mean level of anti-HCV titer upregulation (P = 0.0024); furthermore, among the recipients with BCs (n = 28) and ACR (n = 41), those in the DAA group exhibited significantly higher mean levels of anti-HCV antibody titer upregulation (P < 0.005). Conclusion: In conclusion, we speculated that anti-HCV antibody titer upregulation, which might have been induced by restoration of HCV-specific immune responses with pre-LT DAA therapy, were associated with post-LT allograft injury.

In the European Union (EU), cannabidiol products require pre-marketing authorisation under the novel food regulation. Currently, 19 CBD applications are under assessment at the European Food Safety Authority (EFSA). During the initial assessment of the application files, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) located several knowledge gaps in their 07 June 2022 statement on safety of cannabidiol as a novel food that need to be addressed before the evaluation of CBD can be concluded. Namely, the effect of CBD on the liver, gastrointestinal tract, endocrine system, nervous system, psychological function, and reproductive system needs to be clarified. Nevertheless, the available literature allows a benchmark dose (BMD)-response modelling of several bioassays, resulting in a BMD lower confidence limit (BMDL) of 20 mg/kg bw/day for liver toxicity in rats. Human data in healthy volunteers found increases in the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in a study at 4.3 mg/kg bw/day, which was defined by EFSA NDA panel as a lowest observed adverse effect level (LOAEL). The EFSA NDA panel currently concluded that the safety of CBD as a novel food cannot be evaluated, leading to a so-called clock stop of the applications until the applicants provide the required data. Meanwhile, the authors suggest that CBD products still available as food supplements on the EU market despite the lack of authorisation must be considered as “unsafe”. Products exceeding a health-based guidance value of 10 mg/day must be considered as being “unfit for consumption” (Article 14(1) and (2) (b) of Regulation No 178/2002), while the ones in exceedance of the human LOAEL must be considered “injurious to health” (Article 14(1) and (2) (a) of Regulation No 178/2002).

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer. Low numbers of HCC patients being suitable for liver resection or transplantation and multidrug resistance development during pharmacotherapy leads to high death rates for HCC patients. Understanding the molecular mechanisms of HCC aetiology contributes to development of novel therapeutic strategies for prevention and treatment of HCC. UDP-glucose ceramide glycosyltransferase (UGCG), a key enzyme in glycosphingolipid metabolism, generates glucosylceramide (GlcCer), which is the precursor for all glycosphingolipids (GSLs). Since UGCG gene expression is altered in 0.8 % of HCC tumors, GSLs may play a role in cellular processes in liver cancer cells. Here, we discuss current literature about GSLs and their abundance in normal liver cells, Gaucher disease and HCC. Furthermore, we review the involvement of UGCG/GlcCer in multidrug resistance development, globosides as a potential prognostic marker for HCC, gangliosides as a potential liver cancer stem cell marker, and the role of sulfatides in tumor metastasis. Only a limited number of molecular mechanisms executed by GSLs in HCC are known, which we summarize here briefly.

Overweight/obesity is a growing pandemic nowadays that affects many organs and tissues. We have investigated whether a high-lipid diet provokes an imbalance between type 1 and type 2 angiotensin II (Ang II) receptors signaling, leading to liver alterations associated with previously described cardiovascular and kidney disturbances. Chronic administration of a high-lipid diet can provoke an hepatocardiorenal syndrome as the result of activation of the Ang II→type 1 receptor axis, which is completely counteracted by Ang-(3–4) the allosteric enhancer of the Ang II→type 2 receptor pathway.

We have shown that prebiotic xylo-oligosaccharides (XOS) increased beneficial gut microbiota (GM) and prevented high fat diet-induced hepatic steatosis, but the mechanisms behind these effects are not clear. We studied whether XOS affects adipose tissue inflammation and insulin signaling, and whether the GM and fecal metabolome explain associated patterns. XOS was supplemented or not with high (HFD) or low (LFD) fat diet for 12-weeks in male Wistar rats (n = 10/group). Previously analyzed GM and fecal metabolites were biclustered to reduce data dimensionality and identify interpretable groups of co-occurring genera and metabolites. Based on our findings, biclustering provides a useful algorithmic method for capturing such joint signatures. On the HFD, XOS-supplemented rats showed lower number of adipose tissue crown-like structures, increased phosphorylation of AKT in liver and adipose tissue as well as lower expression of hepatic miRNAs. XOS-supplemented rats had more fecal glycine and less hypoxanthine, isovalerate, branched chain amino acids and aromatic amino acids. Several bacterial genera were associated with the metabolic signatures. In conclusion, the beneficial effects of XOS on hepatic steatosis involved decreased adipose tissue inflammation and likely improved insulin signaling, which were further associated with fecal metabolites and GM.

Metabolic disorders, metabolic syndrome and non-alcoholic fatty liver disease, and depression are those of the most common and debilitating disorders worldwide that often coexist further increasing mortality risks. Although the exact mechanisms underlying this association are poorly known, several hypotheses have been proposed: antipsychotic medication and antidepressants use, diet and physical activity or any other lifestyle factors. However, the high co-occurrence rate of depression and metabolic disorders suggests a possible pathophysiological overlap. In this paper I review several raised mechanisms for this overlap which are the hypothalamic-pituitary-adrenal axis dysregulation, immune alterations with chronic inflammation, as well as oxidative stress. In my view, there is one common thread running through all the aforementioned areas of pathophysiology which is microbiota alteration. So far, several possible interventions in our microbiota have been introduced into clinical practice - dietary and other lifestyle changes, supplementation with prebiotics or probiotics, fecal microbiota transplantation – but with vague indications. A better characterization of the above associations may represent a critical step at phenotyping, and a more targeted approach to the treatment of both depressive and metabolic disorders. At the end of the paper, I give several practical applications for future studies.

The New Zealand brushtail possum (Trichosurus vulpecula), introduced from Australia in the 1850s, is an invasive species that is widespread throughout New Zealand and forms the largest self-sustained reservoir of bovine tuberculosis (Mycobacterium bovis) in the wild. Conservation and agricultural authorities regularly apply a series of population control measures to suppress brushtail possum populations. The evolutionary consequence of more than half a century of intensive population control operations on the species genomic diversity and population structure is hindered by a paucity of available genomic resources for the species. This study is the first to characterise the functional content and diversity of brushtail possum liver and brain cerebral cortex transcriptomes. Raw sequences from hepatic cells and cerebral cortex were assembled into 58,001 and 64,735 transcripts in hepatic cells and cerebral cortex, respectively. Functional annotation and polymorphism assignment of the assembled transcripts demonstrated a considerable level of variation in the core metabolic pathways that represent potential targets for selection pressure exerted by chemical toxicants. This study suggests that the brushtail possum population in New Zealand harbours considerable levels of variation in metabolic pathways that could potentially promote the development of tolerance against chemical toxicants.

Compelling epidemiologic data support the critical role of dietary fructose in the epidemic of obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). The metabolic effects of fructose on the development of metabolic syndrome and NAFLD are not completely understood. High fructose intake impairs copper status, and copper-fructose interactions have been well documented in rats. Altered copper-fructose metabolism leads to exacerbated experimental metabolic syndrome and NAFLD. A growing body of evidence has demonstrated that copper levels are low in NAFLD patients. Moreover, hepatic and serum copper levels are inversely correlated with the severity of NAFLD. Thus, high fructose consumption and low copper availability are considered two important risk factors in NAFLD. However, the causal effect of copper-fructose interactions as well as the effects of fructose intake on copper status remain to be evaluated in humans. The aim of this review is to summarize the role of copper-fructose interactions in the pathogenesis of the metabolic syndrome and discuss the potential underlying mechanisms. This review will shed light on the role of copper homeostasis and high fructose intake and point to copper-fructose interactions as novel mechanisms in the fructose induced NAFLD.

Since coffee has been shown to influence positively the metabolism of subjects with metabolic syndrome (MetS), we aimed to evaluate the short- and long-term effects of a coffee-based supplement on different features of diet-induced MetS. 24 Sprague Dawley rats were divided into control or nutraceuticals groups to receive a high-fat/high fructose diet with or without a mixture of caffeic acid (30 mg/day), trigonelline (20 mg/day), and cafestol (1 mg/day) for 12 weeks. An additional 11 rats were assigned to an acute crossover study. In the chronic experiment, nutraceuticals did not alter body weight or glycemic control but improved fed hyperinsulinemia and HOMA-IR, and plasma adiponectin levels. The impact of nutraceuticals on post-prandial glycemia tended to be more pronounced after acute administration than at the end of the chronic study. Circulating and intrahepatocellular alanine transaminase activity, assessed by hyperpolarized-¹³C NMR spectroscopy, were reduced by coffee nutraceuticals at endpoint. There was also a tendency towards lower liver triglyceride content and histological steatosis score in the intervention group. In conclusion, a mixture of coffee nutraceuticals improved insulin sensitivity and exhibited hepatoprotective effects in a rat model of MetS. Higher dosages with or without caffeine deserve to be studied in the future.

A novel cytoplasmic dye decolorizing peroxidase from Dictyostelium discoideum was investigated that oxidizes anthraquinone dyes, lignin model compounds and general peroxidase substrates like ABTS efficiently. Unlike related enzymes, an aspartate residue replaces the first glycine of the conserved GXXDG motif in Dictyostelium DyPA. In solution, Dictyostelium DyPA exists as a stable dimer with the side chain of Asp146 contributing to the stabilization of the dimer interface by extending the hydrogen bond network connecting two monomers. To gain mechanistic insights, we solved the Dictyostelium DyPA structures in the absence of substrate as well as in the presence of potassium cyanide and veratryl alcohol to 1.7, 1.85, and 1.6 Å resolution, respectively. The active site of Dictyostelium DyPA has a hexa-coordinated heme iron with a histidine residue at the proximal axial position and either an activated oxygen or CN^- molecule at the distal axial position. Asp149 is in an optimal conformation to accept a proton from H₂O₂ during the formation of compound I. Two potential distal solvent channels and a conserved shallow pocket leading to the heme molecule were found in Dictyostelium DyPA. Further, we identified two substrate-binding pockets per monomer in Dictyostelium DyPA at the dimer interface. Long-range electron transfer pathways associated with a hydrogen-bonding network that connects the substrate-binding sites with the heme moiety are described.

C-type lectin CD209/DC-SIGN and CD209L/L-SIGN proteins are distinct cell adhesion and pathogen recognition receptors that mediate cellular interactions and recognize a wide range of pathogens including, viruses such as SARS, SARS-CoV-2, bacteria, fungi and parasites. Pathogens exploit CD209L family proteins to promote infection and evade the immune recognition system. CD209L and CD209 are widely expressed in SARS-CoV-2 target organs and can contribute to infection and pathogenesis. CD209L family receptors are highly susceptible to alternative splicing and genomic polymorphism, which may influence virus tropism and transmission in vivo. The carbohydrate-recognition domain (CRD) and the neck/repeat region represent the key features of CD209L family proteins that are also central to facilitating cellular ligand interactions and pathogen recognition. While, the neck/repeat region is involved in oligomeric dimerization, the CRD recognizes the mannose containing structures present on specific glycoproteins such as those found on the SARS-CoV-2 spike protein. Considering the role of CD209L and related proteins in diverse pathogen recognition, this review article discusses the recent advances in the cellular and biochemical characterization of CD209 and CD209L and their roles in viral uptake, which has important implications in understanding the host-pathogen interaction, the viral pathobiology and driving vaccine development of SARS-CoV-2.

Background and Objectives: The trends in metabolic dysfunction-associated steatotic liver disease (MASLD) and related metabolic dysfunctions in Japan is unknown. Thus, we aimed to clarify the trends of these before the novel coronavirus disease 2019 pandemic in Japan. Materials and Methods: We included Japanese individuals aged 25-79 years who underwent health examinations at our center. We analyzed anthropometry, lifestyle-related disease, and nutritional intake in relation to MASLD trends from 2010-2019. Results: The prevalence of MASLD increased in all ages and body mass index (BMI) classes, reaching 30.3% in males and 16.1% in females, with MASLD accounting for 75% of steatotic liver cases and more than half of all type 2 diabetes mellitus (T2DM) and high waist circumference (HWC) cases. The increase in the prevalence of MASLD was due to an increase in that of steatotic liver itself, and there was no increase in the prevalence of other factors, such as overweight, T2DM, hypertension, and dyslipidemia. The prevalence of glucose metabolic disorders (GMDs) and hypertension decreased. National nutritional data showed an increase in energy intake, total fat, saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids, which correlated with a decrease in GMDs. Salt intake also decreased, which correlated with hypertension. The MASLD group had a higher prevalence of all related metabolic factors than the non-MASLD group, especially HWC, T2DM, and hyperlipidemia. Conclusion: The prevalence of MASLD increased with that of steatotic liver, regardless of age or BMI. A relationship between increased dietary fat, increased steatotic liver, and decreased GMDs was suggested.

To clarify the risk factors for aggravation of esophagogastric varices (EGV) after hepatitis C virus (HCV) eradication with direct-acting antiviral (DAA) therapy, we enrolled 167 consecutive patients with HCV-related compensated cirrhosis who achieved a sustained virological response (SVR) after DAA therapy. During a median of 69 months, EGV was aggravated in 42 (25%) patients despite SVR. The cumulative 1, 3, 5, and 10-year aggravated EGV rates were 7%, 23%, 25%, and 27%, respectively. Multivariate analysis identified platelet count <11.0×10⁴/μL, LSM ≥18.0 kPa, total bile acid ≥33.0 μmol/L, and diameter of left gastric vein (LGV) ≥5.0 mm at HCV eradication as independent risk factors for EGV aggravation post-SVR. In groups that meet all of these risks, the cumulative EGV aggravation rates at 1, 3, and 5 years were 27%, 87%, and 91%, respectively. However, none of the patients who had only one or none of the risk factors experienced EGV aggravation. Platelet count, LSM, total bile acid, and diameter of LGV at HCV eradication were associated with aggravated EGV post-SVR. EGV tends to worsen as two or more of these risk factors increase.

Ulleung County, one of the most medically vulnerable areas in South Korea, requires public attention because of the high incidence of liver cancer. This study was conducted as a part of the Ulleung Liver Cancer Prevention and Management Project. The purpose of this study was to estimate the community prevalence of hepatitis B and C viruses and to identify the associated risk factors. The Project’s interagency workgroup established a procedure for conducting blood sampling and health behavior surveys at the Ulleung Public Community Health Center. A total of 1,792 residents aged 40 years and older voluntarily participated in the study between 2019 and 2022. The hepatitis B surface antigen (HBs Ag) and hepatitis C virus antibody (anti-HCV) positive rates in Ulleung were 7.19% and 1.37%, respectively. Low education level and lifetime smoking were associated with HBsAg positivity, whereas cupping therapy at non-medical institutions was associated with anti-HCV positivity. The odds of HBs Ag positivity were lower among those with tattoos than among those without. There was a difference in the risk factors associated with hepatitis B and C viral infection. While a high HBs Ag positivity rate alone may not fully explain the high incidence of liver cancer in Ulleung, it may be a contributing factor.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths. Classically, liver transplantation (LT) can be curable for HCC tumors within the Milan criteria. Bridging strategies to reduce the dropouts from LT waiting lists or/and to downstage patients who are beyond Milan criteria are widely utilized. We conducted a literature-based review to evaluate the role of systemic therapies as a bridging treatment to liver transplantation (LT) in HCC patients. Tyrosine Kinase Inhibitors (TKIs) can be used as a bridging systemic therapy to LT in patients with contraindication to locoregional liver-directed therapies. Immune Checkpoint Inhibitors (ICIs) treatment can be utilized either as a monotherapy or as a combination therapy with Bevacizumab or TKIs prior to LT. Acute rejection post liver transplantation is a concern in the context of ICIs treatment. Thus, a safe ICI washout period before LT and cautious post-LT immunosuppression strategies are required to reduce post-LT rejections and to optimize clinical outcomes. Nevertheless, prospective clinical trials are needed to establish definitive conclusions about the utility of systemic therapy as a bridging modality prior to LT in HCC patients.

Deep learning (DL) algorithms used for DOTATATE PET lesion detection typically require large, well-annotated training datasets. These are difficult to obtain due to low incidence of gastroenteopancreatic neuroendocrine tumors (GEP-NETs), and the high cost of manual annotation. Furthermore, networks trained and tested with data acquired from site specific PET/CT instrumentation, acquisition and processing protocols have reduced performance when tested with offsite data. This lack of generalizability requires even larger, more diverse training datasets. The objective of this study is to investigate the feasibility of improving DL algorithm performance by better matching the background noise in training datasets to higher noise, out-of-domain testing datasets. 68Ga-DOTATATE PET/CT datasets were obtained from two scanners: Scanner1, a state-of-the-art digital PET/CT (GE DMI PET/CT; n=83 subjects), and Scanner2, an older-generation analog PET/CT (GE STE; n=123 subjects). Set1, the data set from Scanner1 was reconstructed with standard clinical parameters (5 minutes; Q.Clear) and list-mode reconstructions (VPFXS 2, 3, 4, and 5-minutes). Set2, data from Scanner2, representing out-of-domain clinical scans, used standard iterative reconstruction (5 minutes; OSEM). Reconstructed datasets were divided into training, validation, and testing datasets in a 60%, 20%, 20% proportion, and a deep neural network was trained with each: Network1 for Scanner1 and Network2 for Scanner2. DL performance (Network1) was tested with out-of-domain test data (Set2). To evaluate the effect of training sample size, we tested DL model performance using a fraction (25%, 50%, and 75%) of Set1 for training. Scanner1, list-mode 2-minute reconstructed data demonstrated the most similar noise level compared that of Set2, resulting in the best performance (F1=0.713). This was not significantly different compared to the highest performance, upper-bound limit using in-domain training for Network2 (F1=0.755; p-value=0.103). Regarding sample size, the F1 score significantly increased from 25% training data (F1=0.478) to 100% training data (F1=0.713; p&lt;0.001). List-mode data from modern PET scanners can be reconstructed to better match the noise properties of older scanners. Using existing data and their associated annotations dramatically reduces the cost and effort in generating these datasets, and significantly improves the performance of existing DL algorithms. List-mode reconstructions can provide an efficient, low-cost method to improve DL algorithm generalizability.

Hepatitis D virus (HDV) infection represents the most severe form of chronic viral hepatitis. We have shown that the delivery of HDV replication-competent genomes to the hepatocytes using adenoassociated virus (AAV-HDV) as gene delivery vehicles offers a unique platform to investi-gate the molecular aspects of HDV and associated liver damage. Here, we generated HDV ge-nomes modified by site directed mutagenesis aimed to: i) prevent some post-translational modi-fications of HDV antigens (HDAgs) such as Large-HDAg (L-HDAg) isoprenylation or Short-HDAg (S-HDAg) phosphorylation ii) alter the localization of HDAgs within the subcellular compartments and iii) inhibit the right conformation of the delta ribozyme. First, the different HDV mutants were tested in vitro using plasmid-transfected Huh-7 cells and then in vivo in C57BL/6 mice using AAV vectors. We found that Ser 177 phosphorylation and the ribozymal ac-tivity are essential for HDV replication and HDAg expression. Mutation of the isoprenylation domain prevent the formation of infectious particles and increase cellular toxicity and liver dam-age. Finally, altering the intracellular localization od HDAg have a profound on viral replication in vivo but liver toxicity is maintained. Mutation in the nuclear export signal impair the for-mation of infectious viral particles. These findings contribute valuable insights into the intricate mechanisms of HDV biology and have implications for therapeutic considerations

BACKGROUND&AIMS: Hepatitis B virus (HBV) infection remains a major public health problem. The interaction between HBV and the host inflammatory response is an important factor contributing to liver damage and disease development. We compared the correlation between the subclinical index and PBMCs concentration in two groups of pregnant women (HBsAg positive), which are different in HBV DNA concentration in Vietnam. METHODS: The Hierarchical cluster analysis (HCA) was run with 20 different clustering methods on data collected from 80 Vietnamese pregnant women and their babies (60/80 cord blood). RESULTS: In the high viral load group (HBV DNA ≥ 5x10^7 copies/ml), a strong correlation between CBMCs with serum maternal Haemoglobin concentration and maternal platelet and maternal ALT. Their R values are: -0.88, 0.82, and 0.84 with p=8.97E-03, 2.41E-02 and 1.75E-01, respectively. CONCLUSIONS: We found a significant correlation shift of subclinical index between the two groups, which may be important in diagnosing pregnant women with chronic hepatitis B virus infection.

Infectious as well as most non-infectious diseases share certain common molecular mechanisms. Among them, oxidative stress and the subsequent inflammatory reaction are of particular note. Metabolic disorders induced by external agents, be they bacterial or viral pathogens, excessive calorie intake, poor-quality nutrients, or environmental factors, produce an imbalance between the production of free radicals and endogenous antioxidant systems; the consequence being the oxidation of lipids, proteins and nucleic acids. Oxidation and inflammation are closely related, and whether oxidative stress and inflammation represent the causes or consequences of cellular pathology, they produce metabolic alterations that influence the pathogenesis of the disease. In this review we highlight two key molecules in the regulation of these processes: Paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2). PON1 is an enzyme bound to high-density lipoproteins. It breaks down lipid peroxides in lipoproteins and cells, participates in the protection conferred by HDL against different infectious agents, and is considered part of the innate immune system. With PON1 deficiency, CCL2 production increases, which induces migration and infiltration of immune cells in target tissues, and is involved in disturbing normal metabolic function. This disruption involves pathways controlling cellular homeostasis as well as metabolically-driven chronic inflammatory states. Hence, an understanding of these relationships would help improve treatments and, as well, identify new therapeutic targets.

Literature is inconsistent as to how coffee affects the features of the metabolic syndrome (MetS), and which bioactive compounds are responsible for its metabolic effects. We aimed to compare the in-vivo effects of unfiltered coffee with a selected mixture of its compounds on diet-induced MetS. 24 male Sprague-Dawley rats were fed a high-fat (35% W/W) food plus 20% W/W fructose in drinking water for 14 weeks, and were randomized into three groups: control, coffee, or nutraceuticals (5-O-caffeoylquinic acid, caffeic acid, and trigonelline). Coffee or nutraceuticals were provided in drinking water in a dosage equal to 4 cups/day in a human. Compared to the controls, only coffee supplementation decreased total food intake, weight gain, and estimated average plasma glucose. Surrogate measures of insulin resistance (fasting insulin, HOMA-IR, and oral glucose tolerance) were improved at endpoint in the coffee group. Circulating triglyceride levels were also reduced by coffee. Histopathological and quantitative measurements indicated lower grades of liver steatosis after long-term coffee consumption. In conclusion, a combination of phenolic acids and trigonelline was not as effective as coffee per se in improving the components of the MetS. This points to the role of other coffee chemicals and a potential synergism between compounds.

Predicting type 2 diabetes mellitus (T2DM) using phenotypic data with machine learning (ML) techniques has received significant attention in recent years. PyCaret, an ML tool that enables the simultaneous application of 16 different algorithms, was used to predict T2DM using phenotypic variables from the “Nurses’ Health Study” and “Health Professionals’ Follow-up Study” datasets. Ridge classifier, Linear Discriminant Analysis, and Logistic Regression (LR) were the best-performing models for the male-only data subset. For the female-only data subset, LR, Gra-dient Boosting Classifier, and CatBoost Classifier were the strongest models. The AUC, accuracy, and precision were 0.77, 0.70, and 0.70 for males and 0.79, 0.70, and 0.71 for females, respective-ly. The feature importance plot showed that familial history of diabetes (famdb), never having smoked, and high blood pressure (hbp) were the most influential features in females, while famdb, hbp, and current smoking were the major variables in males. In conclusion, PyCaret was used successfully for speed analysis for the prediction of T2DM by simplifying complex ML tasks. Gen-der differences are an important consideration for T2DM prediction. Despite this comprehensive ML tool, phenotypic variables alone may not be sufficient for early T2DM prediction; genotypic variables could also be used in combination for future studies.

Metabolic syndrome (MS), a complex pathology with features like abnormal body fat distribution, insulin resistance, and dyslipidaemia, contributes to higher cardiovascular (CV) risk. A cross-sectional study including 87 individuals, assessed CV risk in elderly patients with type 2 diabetes and MS in Algarve, Portugal. The 10-year CV risk was estimated using the ADVANCE risk score calculator. The reductions in CV risk were estimated by adjusting the data inputted on the online tool to achieve systolic blood pressure (SBP) <130 or <120 mmHg, and LDL-cholesterol <70 mg/dL. Beyond waist circumference, the mean number of clinical features of MS was 3.14±0.84, without significant sex differences. The mean CV risk was 22.5% (CI: 20.3-24.7). Sex-specific analysis showed higher risk in males (24.2%, CI: 21.3-27.0) vs. females (19.7%, CI: 16.2-23.3; p=0.028). Hypothetical risk reductions show that lowering SBP to <130 mmHg could significantly lower the risk by an average of 9.2% (CI: 7.7-10.7), whereas 34.5% of the participants would be out of the diagnostic criteria for MS. When comparing each potential intervention with current risk, all interventions significantly reduce the 10-years CV risk. The study highlights the potential of blood pressure control in reducing CV risk and the importance of multifaceted risk reduction strategies.

Background and Objectives: To investigate the relationship between the SII index and the micro-macro complications and death that develop in the first year and the following 3 years, following the calculation of the index in type 2 diabetic retinopathy patients. Materials and Methods: This study was performed retrospectively with 523 type 2 diabetic retinopathy patients admitted to the endocrinology outpatient clinic of our hospital between January 2019 and December 2019. The demographic, and clinical characteristics of the patients were evaluated using descriptive statistics. Shapiro-Wilk test was used for the normal distribution of quantitative data; Mann-Whitney U, Mc Nemar Chi-square, and Cochran's Q tests were used to analyze SII values between groups and complication rates by years; sensitivity and specificity were determined by ROC analysis and considered statistically significant with a significance level of P

Nuclear DNA mutations, mitochondrial DNA mutations, combined nuclear and mitochondrial DNA defects, and random occurrences are the main causes of mitochondrial disease. Black pigmentation loss is a major sign of Parkinsonism. Because of the loss of dopaminergic neurons in the substantia nigra, it drops to less than 80%. The degree of motor impairment was correlated with the amount of black pigmentation loss. After RNA extraction, reverse transcription is carried out because reverse transcriptase was used to create cDNA. One microliter of total RNA supplemented with IORT Buffer, dNTPs, random hexamers, Multi-Scribe Reverse Transcriptase, and nuclease-free was used to create cDNA. The following was how the reaction was carried out in a thermal cycler: 10 minutes at 25°C, 120 minutes at 37°C, 5 seconds at 85°C, and lastly 4°C. The data was expressed as a v-value, which shows how much the target gene is enriched in comparison to the reference gene. Earlier research using mice injected with functional HtrA2/Omi protease activity revealed similar outcomes, including induced up-regulation of CHOP, decreased mitochondrial function, and early brain cell aging because of an increase in mtDNA deletions. The cell viability of the genotypes exhibits a dmg concentration-dependent effect in these results, suggesting that high content ratios of drug treatment with 6-OHDA may be the cause of cellular content depletion. After 6-OHDA neurotoxin treatment, CHOP is up-regulated. Prior in vitro research has shown that treatment with a model based on 6-OHDA neurotoxin causes the activation of mitochondrial stress pathways, which in turn promotes the death of neurons. 6-OHDA reversibly inhibited complexes I and IV's activities in rat brain cells, which led to dopaminergic neurodegeneration, a defining feature of PD pathogens. As a result, the number of living cells will directly correlate with the dmg concentration, supporting the results of the current study. Real-time PCR can generally demonstrate that the removal of HtrA 2 results in a significant up-regulation of Hsp60 expression when compared to WT cells. This could be linked to a decreased threshold for mitochondrial stress in HtrA2 KO cells, which would explain why, following ADEP4 and ACP5 treatment, Hsp60 is significantly up-regulated in HtrA2 KO cells compared to WT cells.

The three-pronged sliding universal coupling is a new kind of three-pronged coupling. To study its kinematic and dynamic characteristics, directional cosine matrices are utilized as tools to analyze the coordinate systems by establishing simplified geometric models and corresponding motions. Through the analysis of the motions of the input and output shafts and employing the method of single-force element, a set of equilibrium equations for the forces acting on the output shaft and the input shaft are formulated for solution analysis. The research indicates that during the rotation process, there exists a small angular difference between the input shaft and the intermediate shaft, demonstrating the quasi-constant angular velocity characteristics of the new tripod sliding universal coupling. The curves of the forces and torques acting on each component of the coupling approximate sinusoidal curves. The optimal operating angle range for the new tripod universal coupling is at angle , during which the system exhibits good transmission and mechanical performance.

(1) Background: Among the chronic complications of type 2 diabetes mellitus, cancer became the leading cause of death in several countries. Our objective was the determination of whether prevalent type 2 diabetes mellitus is associated with a higher incidence of cancer. (2) Methods: This study is a nationwide analysis performed in Hungary. Study population was divided into a group with type 2 diabetes mellitus and into a non-diabetic group. The primary outcome was the risk related to overall cancer incidence. A key secondary outcome was the overall incidence of cancer in distinct study years. Further outcomes were the annual percent changes. (3) Results: The odds ratio related to the overall incidence of cancer was 2.50 (95% confidence interval: 2.46-2.55, P&lt;0.0001) in patients with diabetes as related to controls. The odds ratio was higher in males than in females. The highest risk was found in the 18-39-year-old subgroup. The annual cancer incidence rate declined in controls, but not in patients with diabetes. Several types of cancer showed a decreasing tendency in non-diabetic controls.; (4) Conclusions: type 2 diabetes is associated with a higher risk of cancer. High risk in young patients with type 2 diabetes suggests that these young individuals should be considered as a risk group.

We show that one of the two important uncertainty principles derived by Maccone and Pati \textit{[Phys. Rev. Lett., 2014]} can be derived for arbitrary maps defined on subsets of $\mathcal{L}^p$ spaces for $1< p<\infty$. Our main tool is the Clarkson inequalities. We also derive a nonlinear uncertainty principle for weak parallelogram spaces and Type-p Banach spaces.

Abstract Background: Metabolic syndrome (MetS) is a complex disorder characterized by insulin resistance (IR), central obesity, atherogenic dyslipidemia and higher glucose levels. It increases the risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), imposing an economic burden on the healthcare system. However, the historical origins of MetS as well as the development and evolution of its definitions have not been conclusively documented in the literature. Aim: This study seeks to enhance the understanding of the developmental trends of MetS during the preceding two decades, placing particular emphasis on the definition, diagnosis and prevalence. Methods: An extensive search was performed from 1920 to 2023 across prominent scientific research engines, including Scopus, PubMed, MDPI, and others. Results: Despite advancements, many aspects of MetS remain inadequately understood. As the understanding of the nature and pathophysiology of MetS progresses, the development and refinement of its diagnostic criteria, and assessment and treatment guidelines will continue. Additionally, there exists significant variation in the global prevalence of metabolic syndrome, ranging from 14 to 39%. This prevalence is projected to increase due to the adoption of less healthy dietary patterns and sedentary lifestyles. The observed disparities in metabolic syndrome prevalence can be attributed to multiple factors, including demographic characteristics. Furthermore, the lack of a standardized definition across studies also contributes to the variation in reported prevalence rates. Conclusion: Further studies focusing on the standardization of the MetS definition across different research are crucial. The establishment of consistent criteria would enhance the reliability and validity of research findings, enabling more meaningful comparisons and interpretations.

I argue that the main feature of elliptical space – the topological identification of its antipodal points – might be behind some observational facts on both cosmological and microscopic scales. I use calculated distance moduli of type-Ia supernovae, which are commonly regarded as “standard candles” for distance measure in cosmology. These are compared with the observational data collected in a catalogue called “Pantheon+”. On the microscopic scale I show that a physical elliptical space, in which the mathematical connectedness between antipodal points is replaced with physical connections via the Einstein-Rosen bridges (also called “wormholes”), gives rise to sub-particle structures similar to J.A. Wheeler’s geons. The interactions between these structures leading to their equilibrium configurations can explain the experimentally observed pattern of properties of elementary particles forming the standard model of particle physics. The answer to the question why we have this particular set of fundamental particles might lie in the fundamental properties of elliptical space.

.Background: Neither radiological phenotypic characteristics nor reconstruction CT scan to study the cranial contour in children with the so called the idiopathic type of West syndrome has been implemented to reach the etiology understanding. Material and Methods: The basic diagnostic measures and the traditional antiepileptic treatments have been applied to these children in accordance with the conventional protocol of investigations and treatment for children with West syndrome. Boys from three unrelated families were given the diagnosis of idiopathic type of West syndrome. Three boys aged 6,7,9 and three parents (age range of 28-41 year) were included in this study. These children and their parents were referred to our orthopedic departments because of variable skeletal deformities. All showed the history of intellectual disabilities, cryptogenic epileptic spasms and fragmented hypsarrhythmia. Recently, variable forms skeletal deformities of flat foot, torticollis and early onset osteoarthritis. We performed detailed clinical and radiological phenotypic characterization of every affected child, siblings and parents. All affected children underwent whole exome sequence analysis Results: The craniofacial phenotype of all children revealed apparent disruption of development of the cranial bones. Palpation of the skull bones showed unusual palpable boney ridges along different sutural locations. A-7-year-old child showed abnormal bulging over the sagittal suture associated with bilateral boney ridges over the sequamosal sutures. Examining his parents, we noticed a similar skull radiographic abnormality in his mother radiographs. A-10-year-old boy showed an extremely narrow frontal area, facial asymmetry and a well palpable ridge over the lambdoid sutures. 3D reconstruction CT scan confirmed the diagnosis of early closure . His mother showed typical radiographic skull phenotype with a history of postadulthood scoliosis. A- 12-year-old boy showed brachycephaly. Investigating his parents revealed a brachycephalic mother with border line intellegence. We affirm that the pattern of inheritance in the three boys was compatible with X-linked recessive pattern of inheritance . Whole exome sequencing showed non definite phenotype/genotype correlation. Conclusion: The aim of this study was fivefold. First, to refute the common usage of the term idiopathic and we affirm that our findings are Novel. Second, it could be possible that West syndrome is a symptom complex rather than a separate diagnostic entity. Third, to further detect the genetic carrier , we explored the connection between the cranial bones in the children with West syndrome with what is seen in parents.. Fourth, the differences in cranial bones abnormalities among every child and another seems to be heterogeneous. Fifth, it seems that the progressive deceleration in the development of this group of children is highly connected to the progressive closure of the cranial sutures.

Herpesvirus is a prevalent pathogen that primarily infects human epithelial cells and has the ability to reside in neurons. In the field of otolaryngology, herpesvirus infection primarily leads to hearing loss and vestibular neuritis, and is considered the primary hypothesis regarding the pathogenesis of vestibular neuritis. In this review, we provide a summary of the effects of herpes virus on cellular processes in both host cells and immune cells, with a focus on HSV-1 as illus-trative examples.

In this article, we establish some new generalized inequalities of Hilbert-type on time scales delta calculus which considered as similar formulas for inequalities of Hilbert type proved by Chang-Jian, Lian-Ying and Cheung [7]. These inequalities will proved by applying Hölder’s inequality, chain rule on time scales and the mean inequality. As special cases of our results (when T = N and T = R), we get the discrete and continuous inequalities. Also, we can obtain other inequalities in different time scale, like T = q^Z, q > 1.

Aronia berries contain antioxidants that may have health promoting properties e.g., demonstrated positive effects on hypertension and dyslipidemia. There is a close link between cardiovascular diseases and hypertension and dyslipidemia, and cardiovascular events are the leading cause of death among subjects with T2D. Thus, we investigated the effect of 8 weeks supplementation with fermented aronia extract (FAE), non-fermented aronia extract (AE) and placebo on cardiovascular risk factors. The extracts were incorporated into snack bars containing 34 g (37%) aronia extract, or 17 g (21%) wheat bran for placebo, as well as raisins and coconut oil. The study was randomized and blinded with a triple-cross-over design. We examined the effects of aronia extracts on blood pressure, adiponectin and high-sensitive C-reactive protein and found no effects. After supplementation with placebo, there were significantly higher total-cholesterol, LDL-cholesterol, and HDL-cholesterol, with the placebo group showing significantly higher increases in total-cholesterol and LDL-cholesterol than the FAE group. Furthermore, we observed an increase in HDL-cholesterol in the AE group and an increase in triglyceride in the FAE group. Thus, we assume that raisins may have increased the participants’ cholesterol levels, however, with both AE and FAE having the potential to prevent this increase.

Melasma is a common skin disorder of acquired hyperpigmentation that appears commonly on the face. Although asymptomatic, melasma causes psychosocial and emotional distress. This study aimed to assess melasma's severity on people with darker skin types, evaluate the effects of melasma on the Quality of Life (QoL), and establish QoL predictors in affected individuals. This was a cross-sectional analytic study that enrolled 150 patients who were diagnosed with melasma from three private dermatology clinics in Durban, South Africa. The severity of melasma and QoL were measured using a Melasma Area and Severity Index (MASI) score, and Melasma Quality of Life scale (MELASQoL), respectively. The factors associated with impaired QoL were also explored using the multivariate method and stepwise regression analysis. MASI score of Masi (β = 0.209, t = 2.628, p < .010), involvement of cheeks (β = -0.268, t = -3.405, p <.001), level of education (β = -0.159, t = -2.029, p =.044) and being menopausal (β = -0.161, t = -2.027, p =.045) were found to be predictors of QoL. A regression model to predict MELASQoL given these four predictors was developed. The significance of the equation can allow remote scoring of MELASQoL based on the four variables.

β3-Adrenoceptors mediate several functions in rodents that could be beneficial for the treatment of obesity and type 2 diabetes. This includes promotion of insulin release from the pancreas, of cellular glucose uptake, of lipolysis, and of thermogenesis in brown adipose tissue. In combination, they lead to a reduction of body weight in several rodent models including ob/ob mice and Zucker diabetic fatty rats. These findings stimulated drug development programs in various pharmaceutical companies, and at least nine β3-adrenoceptor agonists have been tested in clinical trials. However, all of these projects were discontinued due to lack of clinically relevant changes of body weight. Following a concise historical account of discoveries leading to such drug development programs we discuss species differences that explain why β3-adrenoceptors are not a meaningful drug target for the treatment of obesity and type 2 diabetes in humans.

In this study, robust composite solid electrolytes were developed and employed them to enhance the performance of Li-metal batteries significantly. The robust composite solid electrolytes are composed of a soft polymer, poly(ethylene oxide), a Li salt, bis(trifluoromethanesulfonyl)imide (LiTFSI), and super ionic conductive ceramic fillers such as Li1.5Al0.5Ti1.5(PO4)3 (LATP), and Li6.4La3Zr1.4Ta0.6O12 (LLZTO). The main goal of this study is to enhance the electrochemical stability and ionic conductivity. The ionic conductivities of the composite solid electrolytes were found to be 2.08 × 10-4 and 1.64 × 10-4 S cm-1 with the introduction of LATP and LLZTO fillers, respectively. The results prove that the fabricated solid electrolyte was electrochemical stable at voltage exceeding 4.25 V vs. Li/Li+. The internal resistance of the solid electrolyte significantly reduced as compare to gel electrolyte. This reduction can be attributed owing to the alleviation of bulk electrolyte, charge-transfer, and interfacial electrolyte/electrode impedance. When LiFePO4 cathode sheets are coated with a composite solid electrolyte containing LATP powders, the resulting Li-metal battery displays high capacity at 5 C (with a capacity retention of 65.2% compared to the original capacity at 0.2 C) as well as superior cyclic stability and excellent Coulombic efficiency (&gt; 99.5%, over 200 cycles). These results confirm that the composite solid electrolyte acts as a protective layer which have ability to prevent the growth of Li dendrites. Consequently, the fabricated electrolyte configuration can be engineered to enable high energy/power density and electrochemical stable cyclability in Li-metal batteries.

Abstract: The surge of diabetes poses a significant global health challenge, particularly in Oman and the Middle East. Early detection of diabetes is crucial for proactive intervention and improved patient outcomes. This research leverages the power of machine learning, specifically, Convolutional Neural Networks (CNNs), to develop an innovative 4D CNN model dedicated to early diabetes prediction. A region-specific dataset from Oman is utilized to enhance health outcomes for individuals at risk of developing diabetes. The proposed model showcases remarkable accuracy, achieving an average accuracy of 98.49% to 99.17% across various epochs. Additionally, it demonstrates excellent F1 score, recall, and sensitivity, highlighting its ability to identify true positive cases. The findings contribute to the ongoing effort to combat diabetes and pave the way for future research in using deep learning for early disease detection and proactive healthcare.