The paper summarizes the current knowledge about the structure, species, and content differ-ences of β-D-glucans as a storage and functional component, especially of cereal grains. The pa-per also provides comprehensive information on the biosynthesis of this plant cell wall polysac-charide, genetic and non-genetic factors influencing the content variability and indicates the pos-sibilities of breeding modern varieties with a defined content of this metabolite. The final part of the text is also devoted to the influence of significant technological processes applied to cere-als containing β-D-glucans. The chapter discusses the influence of these processes on the content and structure of the polysaccharide and the resulting changes in its physicochemical properties. Part of the discussed issue are the possibilities of effective application of β-D-glucans in different food products.

Brain fog with compromised ability to concentrate has been the most frequent Long Covid (LC) complaint. This is due to an increased transforming growth factor (TGF) β/interferon (IFN)-γ ratio with consequently increased bradykinin (BKN), especially in Caucasian females. Brain and lung blood vessels “leak.” This same ratio is increased in Alzheimer’s disease (AD), but decreased in Parkinson’s disease (PD), because CD4⁺ and CD8⁺ T cells are differentially affected by the invading associated viruses, e.g., SARS CoV2, HIV, Varicella Zoster (VZV) aka Human Herpesvirus 3 (HHV3), HBV, HCV, …. In Covid-19 CD147 receptors on immune cells are critical in generating the increased TGF-β/IFN-γ and those on endothelial cells, platelets, and erythrocytes are critical to the abnormal microvascular blood flow. ACE2 receptors on pneumocytes and enterocytes enable pulmonary and GI entry, initiating gut dysbiosis. Epigenetics, methylation, magnesium, vitamin D, the B vitamins, and antioxidants suggest that these issues can be surmounted. Biochemical, physiologic, and epidemiologic data are analyzed to answer these questions. An LC model is presented and discussed in the context of the most recent research. Suggestions to avoid these and other worrisome concerns are included. Other topics discussed include estrogen, the gut microbiome, type 2 diabetes (T2D), and homocysteine.

This research aims to obtain empirical evidence of the influence of the masculinity of male CEOs on the of research & development, this research seeks to identify the influence of the face of mas-culinity of male CEO’s on the of research & development. The study used a quantitative approach with population and research samples using companies listed on the Indonesia Stock Exchange from 2016 to 2021. The study collected images of faces identified as male CEOs from data from the Indonesia Stock Exchange website and company as utilizing Google searches. The data analysis method in this study used Regression Ordinary Least Square (OLS) with Stata Software. Stata software is one of the regression completion procedures that has a high degree of flexibility in re-search that connects theories, concepts and data that can be done on variables in research. The findings empirically explain that the higher the face value of male CEO masculinity has an impact on reducing research & development costs, and vice versa the lower the face value of male CEO masculinity has an impact on increasing research & development. The practical implications of the research results can help the Indonesian Association of Accountants in developing Financial Accounting Standard No. 19 in Indonesia. The theoretical implications of the research results can explain the Theory of Agency and the Theory of Consistency of Behavior. The policy implications of the results of the study can provide empirical evidence that the higher the facial value of male CEO masculinity has an impact on reducing research & development, while also the lower the face value of male CEO masculinity has an impact on increasing research & development.

Abstract: The genus Acaryochloris is unique among phototrophic organisms due to the dominance of chlorophyll d in its photosynthetic reaction centres and light-harvesting proteins. This allows Acaryochloris to capture light energy for photosynthesis over an extended spectrum of up to ~760 nm in the near infra-red (NIR) spectrum. Acaryochloris sp. has been reported in a variety of ecological niches, ranging from polar to tropical shallow aquatic sites. Here, we report a new Acarychloris strain isolated from an NIR-enriched stratified microbial layer 4-6 mm under the surface of stromatolite mats located in the Hamelin Pool of Shark Bay, Western Australia. Pigment analysis, by traditional spectrometry/fluorometry, flow cytometry and spectral confocal microscopy identify unique patterns in pigment distribution that likely reflect niche adaption. For example, unlike the original A. marina species (type strain MBIC11017), this new strain, Acarychloris LARK001, shows little change in the chlorophyll d/a ratio in response to changes in light wavelength, displays a different Fv/Fm response and lacks detectable levels of phycocyanin. Indeed, 16S rRNA analysis supports the identity of the A. marina LARK001 strain as distinct from the A. marina HICR111A strain first isolated from Heron Island, previously found on the Great Barrier Reef, under coral rubble on the reef flat. Taken together, A. marina LARK001 is a new cyanobacterial strain adapted to the stromatolite matts in Shark Bay.

Adequate serum vitamin D and iron levels are thought to positively influence physical training adaptations and mood. The purpose of this prospective, observational, study was to investigate relationships between serum 25-OH vitamin D and serum ferritin levels with body composition and athlete burnout symptoms. Seventy-three collegiate athletes (49 female) from 7 indoor and outdoor sports were tested pre-season and post-season for: nutrient biomarkers (serum 25-OH vitamin D and serum ferritin) via venipuncture; body composition (total lean mass, bone mineral densi-ty/BMD, and % body fat) via dual energy x-ray absorptiometry (DXA) scans; and athlete burnout symptoms (post-season) via the athlete burnout questionnaire (ABQ). When male and female co-horts were combined, significant relationships were noted between pre-season serum 25-OH vit-amin D versus the change (∆: post-season minus pre-season) in both BMD (r=-0.34;p=0.0003) and % body fat (r=-0.28;p=0.015). Serum ferritin ∆ was significantly associated with lean mass ∆ (r=-0.34;p=0.003). For burnout symptoms, serum 25-OH vitamin D ∆ significantly explained 20.6% of the variance for devaluation of sport in the male cohort only. Across time, serum 25-OH vitamin D levels increased while serum ferritin levels decreased, non-significantly, in both males and fe-males. Relationships between nutrient biomarkers and body composition were opposite of physio-logical expectations.

Background: To determine vitamin D supplementation frequency among infants, factors that influence adherence, and reasons for discontinuation of initiated vitamin D. Methods: This cross-sectional study was conducted using a questionnaire administered to the mothers via a face-to-face interview on 560 infants aged from 1 to 24 months admitted to outpatient clinics from June to December 2017. Results: A total of 351 infants were administered vitamin D, and the rate of supplementation in the first year of life was 83%, while it was only 28% between 13 and 24 months. The rate of vitamin D supplementation was higher among infants who were exclusively formula-fed (p<.05). When the data were analyzed using logistic regression analysis, only visit family physicians seems to be a statistically significant independent variable in increasing supplementation (p<.05). Compared with family refusal, the rate of discontinuation of vitamin D by the healthcare providers was higher after the first year of life (p<.05). The rates of vitamin D discontinuation by healthcare providers, especially by nurses who considered the duration of supplementation adequate, were statistically significantly higher when compared with the fontanel closure and other reasons (p<0.05). Conclusions: The rate of vitamin D supplementation was higher among families who visited family physicians, which suggests the importance of well-baby visits. Since vitamin D supplementation was less common among exclusively breastfed infants, mothers should be educated. Healthcare professionals need further education about the importance of vitamin D supplementation and indications for discontinuation.

Background: Vitamin D was studied in regards to its possible impact on body mass reduction and metabolic changes in adults and children with obesity yet there were no studies assessing the impact of vitamin D supplementation during a weight management programme in children and adolescence. The aim of our study was to assess the influence of 26 weeks of vitamin D supplementation in overweight and obese children undergoing an integrated 12-months’ long weight loss programme on body mass reduction, body composition and bone mineral density. Methods: A double-blind randomized placebo-controlled trial. Vitamin D deficient patients ( <30 ng/ml level of vitamin D) aged 6-14, participating in multidisciplinary weight management programme were randomly allocated to receiving vitamin D (1200 IU) or placebo for the first 26 weeks of the intervention. Results: Out of the 152 qualified patients, 109 (72%) completed a full cycle of four visits scheduled in the programme. There were no difference in the level of BMI change. Although the reduction was greater in the vitamin D vs. placebo group (-4.28 ± 8.43 vs. -2.53 ±6.10) the difference was not statistically significant (p=0.319). Similarly the reduction in fat mass – assessed both using bioimpedance and DEXa was achieved, yet the differences between the groups were not statistically significant. Conclusions: Our study ads substantial results to support the thesis on no effect of vitamin D supplementation on body weight reduction in children and adolescents with vitamin D insufficiency undergoing a weight management programme. Trial registration no: NCT 02828228; trial registration date: 8 June 2016 registered in: ClinicalTrials.gov.

This study aimed to examine the vitamin D status of professional volleyball athletes and to determine its correlation with shoulder muscle strength. We finally included 52 healthy male professional volleyball players (23.2 ± 4.5 years), who were categorized by vitamin D status (<20 ng/mL: deficiency, 20-30 ng/mL: insufficiency, and >30 ng/mL: sufficiency). We examined the strength of the internal rotator (IR) and external rotator (ER) muscles of the shoulder by using isokinetic dynamometer. Fourteen players (26.9%) had vitamin D deficiency, 24 players (46.2%) were vitamin D insufficient, and 14 players (26.9%) were vitamin D sufficient. There was no significant correlation between the vitamin D level and shoulder muscle strength at 60°/s (IR, r = 0.159, p = 0.26; ER, r = 0.245, p = 0.08), and at 180°/s (IR, r = - 0.093, p = 0.51; ER, r = - 0.037, p = 0.79). Moreover, the isokinetic shoulder strengths were not significantly different across the three groups in all settings. In conclusion, vitamin D insufficiency was common in elite volleyball players. Though not being associated with isokinetic muscle weakness, vitamin D should be regularly monitored and supplemented in young elite athletes, considering its importance on musculoskeletal health.

Since it was proposed, the Robot Operating System (ROS) has fostered solutions for various problems in robotics in the form of ROS packages. One of these problems is Simultaneous Localization and Mapping (SLAM), a problem solved by computing the robot pose and a map of its environment of operation at the same time. The increasingly availability of robot kits ready to be programmed and also of RGB-D sensors often pose the question of which SLAM package should be used given the application requirements. When the SLAM subsystem must deliver estimates for robot navigation, as is the case of applications involving autonomous navigation, this question is even more relevant. This work introduces an experimental analysis of GMapping and RTAB-Map, two ROS compatible SLAM packages, regarding their SLAM accuracy, quality of produced maps and use of produced maps in navigation tasks. Our analysis aims ground robots equipped with RGB-D sensors for indoor environments and is supported by experiments conducted on datasets from simulation, benchmarks and from our own robot.

Chronic kidney disease (CKD) is a major non-communicable disease associated with high rates of premature morbidity and mortality. The prevalence of hypovitaminosis D (deficiency of 25(OH)D or 25D) is greater in racial/ethnic minorities and in patients with CKD than the general population. Low 25D is associated with bone and mineral disorders as well as immune, cardiometabolic and cardiovascular (CV) diseases. Thus, it has been suggested low 25D contributes to the poor outcomes in patients with CKD. The prevalence of hypovitaminosis D rises progressively with advancing severity of kidney disease with over 30% of patients with CKD stage 3 and 70% patients with CKD stage 5 estimated to have low levels of 25D. This report describes several of the abnormal physiologic and counter-regulatory actions related to low 25D in CKD such as those in oxidative stress and inflammatory systems, and some of the preclinical and clinical evidence or lack of thereof of normalizing serum 25D levels to improve outcomes in patients with CKD, and especially for the high risk subset of racial/ethnic minorities who suffer from higher rates of advanced CKD and hypovitaminosis D.

The aim of this study was to develop a valid and reliable questionnaire to assess vitamin D-related knowledge, attitude and practice (KAP) in Iranian adults who may be at increased risk of vitamin D deficiency. This study was conducted on 527 subjects, aged ≥20 years from Public health care centers in Tehran, Iran. Based on results of literature review and in-depth interviews, the 38-item vitamin D-related KAP questionnaire with four subscale was developed: 1) general knowledge; 2) nutritional knowledge; 3) attitudes; 4) behaviors. Validity of the developed vitamin D-KAP questionnaire was assessed, utilizing face, content, and construct validity methods. Internal consistency was calculated to assess reliability of the current developed questionnaire. A total of 572 (54.1% female) adults, aged 30.2±7.9 years, participated in the study. All items were perceived as relevant and comprehendible by participants. Content validity was confirmed by the panel of experts. The internal consistency, as measured by Cronbach’s alpha coefficients, exceeded the minimum reliability standard of 0.60 for four subscales. The EFA suggested a four-factor construct and the results of the CFA indicated acceptable fit indices for the proposed model. No ceiling effects were observed except for general knowledge (1.2%). Floor effects detected were 0, 1.1, 2.4, and 8.7% for practice, attitude, general knowledge, and nutrition knowledge, respectively. General knowledge had the highest score (79.59±14.52) and nutrition knowledge, the lowest score (42.58±20.40) among the four sub-scales. Results confirm the initial validity and reliability of the vitamin D-related knowledge, attitude and practice questionnaire. Further investigations in different urban and rural population are recommended.

Organic light-emitting diodes (OLEDs) have garnered considerable attention in academic and industrial circles due to their potential applications in flat panel displays and solid-state lighting technologies, leveraging the advantages offered by organic electroactive derivatives over their inorganic counterparts. The thin and flexible design of OLEDs enables the development of innovative lighting solutions, facilitating the creation of customizable and contoured lighting panels. Among the diverse electroactive components employed in the molecular design of OLED materials, the benzophenone core has attracted much attention as fragment for synthesis of organic semiconductors. On the other hand, the benzophenone also functions as a classical phosphor with high intersystem crossing efficiency. This characteristic makes it as compelling candidate for effective reverse intersystem crossing, potentially leading to the development of thermally activated delayed fluorescent (TADF) emitters. These emitting materials witnessed a pronounced interest in recent years due to their incorporation in metal-free electroactive frameworks and the capability to convert triplet excitons into emissive singlet excitons through reverse intersystem crossing (RISC), consequently achieving exceptionally high external quantum efficiencies (EQEs). This review article comprehensively overviews the synthetic pathways, thermal characteristics, electrochemical behaviour and photo-physical properties of the derivatives based on benzophenone. Furthermore, we explore their applications in OLED devices, both as host materials and emitters, shedding light on the promising opportunities that benzophenone-based compounds present in advancing OLED technology.

The rapid growth of the global wearable technologies market is projected to reach $61.30 billion by 2030 which reflects a shift towards personalised health monitoring embedded in everyday activities. This paper explores the potential of embroidered interdigitated transducer (IDT)-based sensors for non-invasive, continuous monitoring of human biomarkers, particularly glucose levels, in human sweat. The study employs innovative embroidery techniques to create flexible fabric-based sensors with gold-coated IDTs. Experimental results demonstrate the sensor’s capability to detect water droplets and glucose concentrations, showcasing promising applications for health monitoring. The embroidered IDT-based sensors offer a unique approach for seamless integration into clothing, paving the way for personalised, continuous health data capture.

Mangifera indica (mango), a member of the Anacardiaceae family, is renowned for its diverse pharmacological properties, encompassing antidiabetic, antioxidant, antiviral, cardiotonic, hypotensive, and anti-inflammatory effects. The present study delves the insulin-releasing and glucose-lowering potential of the ethanolic extract of Mangifera indica (EEMI) leaves in streptozotocin (STZ)-induced type 2 diabetic rats, concurrently investigating its phytoconstituents. EEMI's effects on insulin secretion were measured using BRIN BD11 β-cells and isolated mouse islets. It’s enzymatic inhibitory properties on carbohydrate digestion, glucose absorption, and free radicals were investigated using starch digestion, glucose diffusion and DPPH assay methods. In-vivo parameters including lipid profile and liver glycogen content were assessed on streptozotocin-induced type 2 diabetic rats. EEMI exhibited a dose-dependent increase in insulin secretion from clonal pancreatic BRIN BD11 β-cells and isolated mouse islets. EEMI inhibited starch digestion, glucose diffusion over time and DPPH activity in vitro. In acute in vivo studies, EEMI improved food intake, oral glucose tolerance. Moreover, following 28 days of treatment with EEMI, a remarkable amelioration in body weight, fasting blood glucose, plasma insulin, liver glycogen content, total cholesterol, triglyceride, LDL, VLDL and HDL levels were observed. Further phytochemical analysis with EEMI identified the presence of alkaloids, tannins, saponins, steroids, glycosides, flavonoids, and reducing sugar. The synergistic effects of EEMI, potentially attributable to naturally occurring phytoconstituents, hold promise for the development of enriched antidiabetic therapies, offering a promising avenue for the management of type 2 diabetes.

Background: RNA helicase DHX15 plays a significant role in vasculature development and lung metastasis in vertebrates. In addition, several studies have demonstrated the overexpression of DHX15 in the context of hepatocellular carcinoma. Therefore, we hypothesized that this helicase may play a significant role in liver regeneration, physiology and pathology. Methods: Dhx15 gene deficiency was generated by CRISPR/Cas9 in zebrafish and by TALEN-RNA in mice. FANA Antisense-Oligonucleotides were used to silence Dhx15 in wild-type mice. The hepatocellular carcinoma tumor induction model was generated by subcutaneous injection of Hepa 1-6 cells. Results: Homozygous Dhx15 gene deficiency was lethal in zebrafish and mouse embryos. Dhx15 gene deficiency impaired liver organogenesis in zebrafish embryos and liver regeneration after partial hepatectomy in mice. Also, heterozygous mice presented decreased number and size of liver metastasis after Hepa 1-6 cells injection compared to wild-type mice. Dhx15 gene silencing with FANA Antisense-Oligonucleotides in wild-type mice resulted in 80% reduced expression in the liver and a significant reduction in other major organs. In addition, Dhx15 gene silencing significantly hindered primary tumor growth in the hepatocellular carcinoma experimental model. Regarding the potential use of DHX15 as a diagnostic marker for liver disease, patients with hepatocellular carcinoma showed increased levels of DHX15 in blood samples compared with subjects without hepatic affectation. Conclusion: Dhx15 is a key regulator of liver physiology and organogenesis, is increased in the blood of cirrhotic and hepatocellular carcinoma patients and has a key role in controlling hepatocellular carcinoma tumor growth and expansion in experimental models.

Achieving synchronization between the central and peripheral body clocks is essential for ensuring optimal metabolic function. Meal timing is an emerging field of research that investigates the influence of eating patterns on our circadian rhythm, metabolism, and overall health. This narrative review examines the relationship between meal timing, circadian rhythm, clock genes, circadian hormones, and metabolic function. It analyzes existing literature and experimental data to explore the connection between mealtime, circadian rhythms, and metabolic processes. The available evidence highlights the importance of aligning mealtime with the body’s natural rhythms to promote metabolic health and prevent metabolic disorders. Specifically, studies show that consuming meals later in the day is associated with a elevated prevalence of metabolic disorders, while early time-restricted eating, such as having an early breakfast and an earlier dinner, improves levels of glucose in the blood and substrate oxidation. Circadian hormones, including cortisol and melatonin, interact with mealtimes and play vital roles in regulating metabolic processes. Cortisol, aligned with dawn in diurnal mammals, activates energy reserves, stimulates appetite, influences clock gene expression, and synchronizes peripheral clocks. Consuming meals during periods of elevated melatonin levels, specifically during the circadian night, has been correlated with potential implications for glucose tolerance. Understanding the mechanisms of central and peripheral clock synchronization, including genetics, interactions with chronotype, sleep duration, and hormonal changes, provides valuable insights for optimizing dietary strategies and timing. This knowledge contributes to improved overall health and well-being by aligning mealtime with the body’s natural circadian rhythm.

Chia seed, high in dietary-fiber and protein, may have potential to increase satiety. However, previous studies are confounded by differences in energy intake, and none investigated doses &lt;7g. We compared the subjective appetite and glycaemic responses elicited by 30g cookies containing 0, 3, 5 or 7g chia seed (CS0, CS3, CS5 or CS7, respectively, 140-150kcal, 7-8g fat, 4g protein, 0-2g dietary-fiber, 16g available-carbohydrate) using a randomized, double-blind, cross-over design. Overnight-fasted heathy adults (24 males, 22 females; mean±SD age 37±13y; BMI 27.4±3.9kg/m²) consumed test-cookies and had appetite and plasma-glucose measured before and intermittently for 3h after eating. Data were analyzed by ANOVA with Tukey’s test to adjust for multiple comparisons; the criterion for significance was 2-tailed p&lt;0.025 for the primary endpoints of total area under the curve (tAUC0-3h) for hunger and fullness. Hunger tAUC0-3h was similar among treatments (p=0.49) but fullness differed (p=0.019) with tAUC0-3h after CS3&gt;CS7 (mean±SEM) (140±9 vs 122±10mm×h, p&lt;0.025). Mean incremental glucose AUC0-2h after CS3, CS5 and CS7, respectively, were 22%, 23% and 30% less than CS0 (p&lt;0.05). Thus, although chia reduced glycemic responses, we were unable to demonstrate a significant effect of ≤7g chia seed on the primary endpoints of hunger or fullness tAUC0-3h versus control.

Objectives and Background: Gestational diabetes (GDM) is a common pregnancy complication, defined as a glucose intolerance diagnosis during pregnancy. GDM is strongly associated with adverse fetal and maternal outcomes. In Germany, to screen and diagnose GDM we use a 1-hour 50g oGCT (oral glucose challenge test) followed by a 2-hour 75g oGTT if the first was pathological. This analysis examines the correlation of 75g oGTT glucose levels and fetomaternal outcome. Methods: Data of 1664 patients from a gestational diabetes consultation clinic at the Charité University hospital in Berlin, Germany, were analyzed retrospectively from 2015 until 2022. The 75g oGTT blood glucose levels were categorized into isolated fasting hyperglycemia (GDM-IFH), isolated post-load hyperglycemia (GDM-IPH) and combined hyperglycemia (GDM-CH), using the levels of the fasting, 1-hour and 2-hour values after glucose application. These subtypes were compared regarding baseline characteristics as well as fetal and maternal outcome. Results: GDM-IFH and GDM-CH women displayed higher preconceptional BMI and required insulin therapy more frequently (p<0,001). The GDM-IFH group was at higher risk of having a primary cesarean section (p=0,047), while GDM-IPH women were significantly more likely to have an emergent cesarean section (p=0,013). The offspring of GDM-IFH and GDM-CH women were born with a significantly higher mean birthweight (p<0,001) and birth weight percentiles (p<0,001) and were at increased risk of being large for gestational age (LGA) (p=0,004). Women from the GDM-IPH group delivered significantly more neonates who were small for gestational age (p=0,027) or with low fetal weight <30th percentile (p=0,003). Conclusion: This analysis shows a strong association between glucose response pattern in the 75g oGTT and adverse perinatal fetomaternal outcome. The differences among the subgroups, specifically concerning insulin therapy, mode of delivery and fetal growth, suggest an individualized approach in prenatal care after a GDM diagnosis.

Metabolic changes are an important component of tumor cell progression. Tumor cells adapt to environmental stresses via changes to carbohydrate and lipid metabolism. Autophagy, a physiological process in mammalian cells that digests damaged organelles and misfolded proteins via lysosomal degradation is closely associated with metabolism in mammalian cells acting as a meter of cellular ATP levels. In this review, we discuss the changes in glycolytic and lipid biosynthetic pathways in mammalian cells and their impact on carcinogenesis via the autophagy pathway. Also, we discuss the impact of these metabolic pathways on autophagy in lung cancer.

Abstract: Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation within hepatocytes, but the relative contributions of different macronutrients is still unclear. We inves-tigated the impact of fatty acids, glucose and fructose on lipid accumulation in primary human hepatocytes (PHH) and three different hepatoma cell lines: HepG2, Huh7 and McA-RH7777 (McA). Cells were treated for 48 hours with fatty acids (0 or 200μM), glucose (5mM or 11mM) and fructose (0mM, 2mM or 8mM). Lipid accumulation was measured via Nile Red staining. All cell types accumulated lipid in response to fatty acids (P<0.001). PHH and McA, but not HepG2 or Huh7 cells, accumulated more lipid with 11mM glucose plus fatty acids (P=0.004, fatty acid x glucose interaction, for both), but only PHH increased lipid accumulation in response to fructose (P<0.001). Considerable variation was observed between PHH cells from different individuals. Lipid accumulation in PHH was increased by insulin (P=0.003) with inter-individual variability. Similarly, insulin increased lipid accumulation in both HepG2 and McA cells, with a bigger response in McA in the presence of fatty acids (P<0.001 for fatty acid x insulin). McA were more insulin sensitive than either HepG2 or Huh7 cells in terms of AKT phosphorylation (P<0.001 insulin x cell type interaction). Hence glucose and fructose can contribute to the accumulation of lipid in PHH with considerable inter-individual variation, but hepatoma cell lines are not good models of PHH.

The glucose-insulin regulatory system and its glucose oscillations is a recurring theme in the literature because of its impact on human lives, mostly the ones affected by diabetes mellitus. Several approaches were proposed, from mathematical to data-based models, with the aim of modeling the glucose oscillation curve. Having such a curve, it is possible to predict, when injecting insulin in type 1 diabetes (T1D) individuals. However, the literature presents prediction horizons no longer than 6 hours, which could be a problem considering their sleeping time. This work presents Tesseratus, a model that adopts a multi-agent approach to combine machine learning and mathematical modeling to predict the glucose oscillation up to 8 hours. Tesseratus uses the pharmacokinetics of insulins and data collected from T1D individuals. Its outcome can support endocrinologists while prescripting daily treatment for T1D individuals, and provide personalized recommendations for such individuals, to keep their glucose concentration in the ideal range. Tesseratus brings pioneering results for prediction horizons of 8 hours for nighttime, in an experiment with seven real T1D individuals. It is our claim that Tesseratus will be a reference for classification of glucose prediction model, supporting the mitigation of short- and long-term complications in the T1D individuals.

The integration of metal nanoparticles and solid carriers can achieve ideal stability, high load and good conductivity. In this work, copper nanoparticles (Cu NPs) were sequentially deposited on a cobalt metal-organic framework (Co-MOF) by bonding with exposed imino groups, followed by a reduction reaction to prepare a new Cu@Co-MOF composite. Cu@Co-MOF acts as a non-enzymatic electrochemical sensor to detect glucose (Glu) in an alkaline medium. The composite working electrode of Cu@Co-MOF/GCE (GCE = glassy carbon electrode) improves the electrocatalytic activity for Glu oxidation. Cu@Co-MOF/GCE shows excellent electrocatalytic performances in Glu concentration ranging 0.005~1.8 mmol∙L⁻¹ (mM): the sensitivities are 282.89 μA∙mM⁻¹∙cm⁻² in 0.005-0.4 mM Glu and 113.15 μA∙mM⁻¹∙cm⁻² in 0.4-1.8 mM Glu respectively with low detection limit of 1.6 μM (S/N = 3) and high selectivity and stability.

To cope the high glycemic variability (GV) is crucial in the management of multiple daily insulin (MDI) in diabetes. We compared the effect of low dose metformin 750mg/d adding vildagliptin 100mg/d (DPP4+LMET) or the high dose metformin 1500mg/d (HMET), in type 2 diabetes (T2D) with MDI, evaluating GV by continuous glucose monitoring (CGM). Single center, open-label, 12 weeks - 2 period crossover design. Twenty T2D with inadequately controlled (7.0% <HbA1c ≦9.0%) with MDI + LMET were enrolled. Primary endpoints were GV and hypoglycemia derived from CGM performed after each 12 weeks treatment periods. There was no significant difference in HbA1c, body weight changes, total daily dose of insulin. DPP4+LMET compared to the HMET, significantly reduced the calculated GV value, mean (7.15±1.3 vs 7.82±1.6, p<0.05), standard deviation (1.78±0.55 vs 2.27±1.11, p=0.03), continuous overlapping net glycemic action (6.44±1.28 vs 7.12±1.69, p<0.05), J-Index (26.7±11.0 vs 34.9±19.8, p<0.05), high blood glucose index (3.01±1.96 vs. 6.73±4.85, p=0.02), and mean amplitude of glycemic excursions (4.53±1.35 vs 5.50±2.34, p=0.03). The GV metrics with hypoglycemia and nocturnal hypoglycemia were not significantly different. DPP4+LMET decreased GV associated with hyperglycemia. Adding DPP4 inhibitor to the lower dose of metformin is an alternative approach to the stable GV in MDI.

We assessed the growth performance, physiological traits, and gene expressions in steers fed with dietary rumen-protected L-tryptophan (RPT) under cold environment. Eight Korean native steers were assigned to two dietary groups, no RPT (Control) and RPT (0.1% RPT supplementation on a dry matter basis), 6 wks. Maximum and minimum temperatures throughout the experiment were 6.7°C and -7.0°C, respectively. Supplementation of 0.1% RPT to a total mixed ration did not increase body weight but had positive effects of elevating average daily gain (ADG) and reducing the feed conversion ratio (FCR) at day 27 and 48. Metabolic parameter showed higher glucose level (at day 27) in the 0.1% RPT group compared to the control group. Real-time PCR analysis showed no significant differences in the expression of muscle (MYF6, MyoD, and Desmin) metabolism genes between the two groups, whereas the expression of fat (PPARγ, C/EBPα, and FABP4) metabolism genes was lower in the 0.1% RPT group than in the control group. Thus, we demonstrate that long-term (6 wks) dietary supplementation of 0.1% RPT was beneficial owing to enhanced growth performance by increasing ADG and glucose level, decreasing FCR, and maintaining homeostasis in immune responses in beef steers during cold environment.

An autonomous endogenous time-keeping is ubiquitous across many living organisms known as circadian clock when it has a period of about 24 hours. Interestingly, the fundamental design principle with a network of interconnected negative and positive feedback loops is conserved through evolution, although the molecular components differ. Filamentous fungus \textit{Neurospora crassa} is a well established chrono-genetics model organism to investigate the underlying mechanisms. The core negative feedback loop of the clock of \textit{Neurospora} is composed of the transcription activator White Collar Complex (WCC) (heterodimer of WC1 and WC2) and the inhibitory element called FFC complex which is made of FRQ (Frequency protein), FRH (Frequency interacting RNA Helicase) and CK1a (Casein kinase 1a). While exploring their temporal dynamics we investigate how limit cycle oscillations arise and how molecular switches support self-sustained rhythms. We develop a mathematical model of 10 variables with 26 parameters to understand the interactions and feedbacks among WC1 and FFC elements in nuclear and cytoplasmic compartments. We performed control and bifurcation analysis to show that our novel model produces robust oscillations with a wild-type period of 22.5 hrs. Our model reveals a switch between WC1 induced transcription and FFC assisted inactivation of WC1. Using the new model we also study possible mechanisms of glucose compensation. A fairly simple model with just 3 non-linearities helps to elucidate clock dynamics revealing a mechanism of rhythms production. The model can further be utilized to study entrainment and temperature compensation.

Worldwide epidemiological data indicates insufficient diagnosis of diabetes as an increasing problem of public health. Searching for solutions in this disadvantageous situation, occupational medicine health services seem to open up a unique opportunity to recognize some abnormalities in early steps, especially among the asymptomatic working-age population. 316 workers underwent obligatory prophylactic examinations. In patients with twice assayed FGL ≥ 126 mg/dl (7.0 mmol/l) the additional intervention was implemented, including further diagnostic process and therapy in General Practice (GP), followed by examination by an occupational health specialist within 3 months. The diagnosis of previously unknown diabetes was established among 2.5% of examined workers. All patients referred to the GP due to detected glycaemia impairment visited their doctor and finished the diagnostic process, took up therapy constrained by the occupational health physician to show the effects of intervention within 3 months. Prophylactic medical check-ups allow improved compliance and medical surveillance over glycaemia impairment in patients with prediabetes states, unknown diabetes or uncontrolled clinical course of diabetes. Considering fasting glucose level during mandatory prophylactic examination helps effective prevention of diabetes and its complications and thus give public health system benefits.

Facilitative glucose transporters (GLUT) are transmembrane transporter of proteins involved in glucose transport across the plasma membrane. To date, there is no information about glucose transporter 2 (GLUT2) in blunt snout bream (Megalobram aamblycephala). In this study, GLUT2 were cloned and characterized from blunt snout bream, and its-expression in response to diets with different carbohydrate levels (17.1%; 21.8%; 26.4%; 32.0%; 36.3% and 41.9% of dry matter). In this study, the full-length cDNA of GLUT2 was 2577 bp, including a 5’-untranslated region (UTR) of 73 bp, a 3’-UTR of 992 bp, and an open reading frame of 1512 bp, encoding a polypeptide of 503 amino acids with predicted molecular weight of 55.046 kDa and theoretical isoelectric point of 7.52. GLUT2 has twelve across the membrane area locating at 7-29; 71-93; 106-123; 133-155; 168-190; 195-217; 282-301; 316-338; 345-367; 377-399; 412-434; 438-460 aimo acids respectively. Conservative structure domains located at 12-477 aimo acids belonging to sugar porter family major facilitator superfamily (MFS) transporter. The blunt snout bream GLUT2 showed high identity to their orthologs in other fish species and mammals. Quantitative real-time (qRT)-PCR assays revealed that GLUT2 expression was high in the liver, intestine and kidney; highest in the liver. Compared with the control group (17.1%), high dietary carbohydrate levels (32.0%; 36.3% and 41.9%) resulted in high plasma glucose at 3h after feeding, but high plasma glucose were back to basal at 24h after feeding. Furthermore, high dietary carbohydrate levels significantly improved the glycolysis and inhibitied gluconeogenesis by augmentation of GK and PK expression, inhibition of PEPCK and G6P mRNA levels (P<0.05). However, GLUT2; GK; PK; PEPCK and G6P mRNA levels were back to basal.

Organic light-emitting diodes (OLEDs) have ushered in a technological revolution with their remarkable impact on diverse sectors of our daily lives. These versatile devices known for their outstanding display and lighting capabilities, have become indispensable components in various industries including smartphones, tablets, televisions, and automotive applications. This paper delves into the development of a group of twisted donor-acceptor-donor (D-A-D) derivatives incorporating bicarbazole and benzophenone structures for potential use as blue emitters in OLEDs. The synthesized compounds, namely DB14, DB23 and DB29, were designed with various alkyl side chains to enhance their film forming properties as for blue emitters. Characterization and evaluation of these derivatives included photophysical, electrochemical, thermal, and electroluminescent analysis. Some of the OLED devices incorporating these emitters demonstrated promising performance with maximum current efficiency (CEmax) of 2.6 cd/A and external quantum efficiency (EQEmax) of 5.3%. Notably, the DB23 emitter exhibited the highest EQE among all devices. The study also emphasizes the influence of host-guest energy transfer, optimal doping concentrations, and molecular structures on device performance. This research not only contributes to the understanding of advanced OLED materials but also provides insights into designing efficient blue emitters for future display and lighting applications, thereby advancing the field of organic electronics.

Three different fields intersect in search of an understanding of the point-of-origin of modern-age diseases: 1) D-amino acids and their role under stress conditions; 2) evolutionary origin of the mitochondrion organelle in the eukaryotic cell; and 3) gut microbiota and human healthHere it is first suggested that D-amino acids function as universal signaling agents, after having evolved as prokaryotic communication, part of an organic communication process that governs the basic activities of all the cells and coordinates cell action.Mitochondria (symbiotic prokaryotic organelles), are creative source of D-amino acids as signaling agents in the central nervous system and in the neuroendocrine systems.Amino acids racemases catalyzes the conversion between the L-enantiomers ( protein building blocks) into D-enantiomers (signaling agents).It is suggested that hectic modern life may affect human health by causing stress to the gut microbiota. These affected, gut microbiota then secrete D-amino acids that enter the blood stream, as signaling agents, causing communication errors in the central nervous system, and in the neuroendocrine systems due to excessive quantity of D-amino acids.Treating gut microbiota with inhibitors of amino acids racemases or finding D-amino acid scavengers may be used in developing novel therapeutic strategies for diseases related to the central nervous system and neuroendocrine systems caused by stressed gut microbiota.

Phenotyping is the task of measuring plant attributes for analyzing the current state of the plant. In agriculture, phenotyping can be used to make decisions concerning the management of crops, such as the watering policy, or whether to spray for a certain pest. Currently, large scale phenotyping in fields is typically done using manual labor, which is a costly, low throughput process. Researchers often advocate the use of automated systems for phenotyping, relying on the use of sensors for making measurements. The recent rise of low cost, yet reasonably accurate, RGB-D sensors has opened the way for using these sensors in field phenotyping applications. In this paper, we investigate the applicability of 4 different RGB-D sensors for this task. We conduct an outdoor experiment, measuring plant attribute in various distances and light conditions. Our results show that modern RGB-D sensors, in particular, the Intel D435 sensor, provides a viable tool for close range phenotyping tasks in fields.

Aging is the results of several complex and multifactorial processes, where several agents contribute to increase intrinsic vulnerability and susceptibility to age-related diseases. The hallmarks of aging are a set of biological mechanisms, finely regulated and strictly interconnected, initiating or contributing to biological changes anticipating several age-related diseases. The complex network of cellular and intercellular connections between the hallmarks might represent a possible target for the research of agents with pleiotropic affects. Vitamin D (VitD) is known to have positive impact not only on muscle and bone health, but also on several extra-skeletal districts, due to the widespread presence of VDRs (VDR). VitD and VDR could be molecules potentially targeting the hallmark of aging network. To date, evidence about the potential effect of VitD on the hallmark of aging is scarce in humans and mainly based on preclinical models. Although underpowered and heterogeneous, in-human studies seems to confirm the modulatory effect of VitD on some hallmarks aging and diseases. However, more investigations are needed to clarify the pleiotropic effects of VitD and its impact on the hallmark of aging, hopefully highlighting the courses for translational applications and potential clinical conclusions.

Cathode materials based on SrCoO3- perovskite-type oxides hold great potential, given the huge oxygen permeability exhibited by the cubic phase of this oxide, which must be stabilized though suitable cationic substitutions. We present here two novel materials of the series Sr1-xYxCoO3- (x= 0.1, 0.2), prepared by solid state reactions. The crystalline structure was explored by neutron powder diffraction. At RT, we identified a subtle tetragonal superstructure, yet preserving the wanted framework of vertex-sharing CoO6 octahedra. A noteworthy result of the neutron analysis is the presence of conspicuous amounts of oxygen vacancies, ordered in layers and responsible for the formation of the mentioned superstructure. The stability was investigated by thermal analysis, using thermogravimetry (TGA). The electrical conductivity gave a maximum value of 800 °C of 122 S·cm–1. To determine the resistance associated with the oxygen reduction reaction (ORR), electrochemical impedance spectroscopy as a function of temperature was carried out, finding a value for the activation energy of Ea= 0.82 eV. This is a much lower value than that usually obtained for cathodes with a high catalytic activity for the oxygen reduction reaction. In single-cell tests, the materials generated a power density up to 0.25 Wcm−2 at 800ºC, using pure H2 as fuel. All these features make this perovskite a suitable candidate as cathode material in intermediate-temperature SOFCs

Long Covid has become a blight, its economic consequences overwhelming. But Long Covid (LC) may represent persistent Covid-19 in those with preexisting Candida overgrowth (CO). The features shared by both are striking. LC may be a growing subset of CO. The altered tryptophan metabolism encountered in LC is driven by IFN-γ in reaction to CO. Females are robust producers of IFN-γ, yet estrogen promotes CO.The consequent decline in serotonin and melatonin triggers the mood swings and sleeplessness respectively in LC. The low serotonin, the primary messenger in the gut brain axis, creates autonomic dysfunction. The CO induced gut dysbiosis and leaky gut initiate an autoimmune path. TNFα seen in both LC and this opportunistic yeast is at the center of the cytokine triad that leads to neurodegeneration. The Western diet, high in carbohydrates, alcohol, and glutamate, is exploited by this commensal turned parasite. Residual SARS CoV2 and Candida generate abundant ROS, inducing mitochondrial dysfunction. Alcohol tastes different for many with LC, because acetaldehyde requires functioning hepatic mitochondria. This article delves into the complex physiology and biochemistry that drive the symptoms of this conspicuous connection. Recent research has revealed innovative approaches that might address this global scourge, including D-mannose for the immune dysfunction and butyrate for the gut dysbiosis created by and seen in both LC and intestinal Candidiasis.

Revenue-sharing (RS) contracts are a common approach to incentivize innovation of upstream suppliers by addressing the uneven profit distribution between upstream and downstream firms. Considering the possible overconfidence characterizing decision makers in the supply chain, we investigate the effect of the RS contract and the tendency of overconfidence of supply chain members on the investment in R&D of key components of products in the context of an upstream supplier that is the leader in the R&D and production of key components. We find that regardless of the bargaining power of either party, a RS contract can increase the R&D investment in key components. Regarding the effects of overconfidence of either downstream manufacturer or up-stream supplier, it can increase the R&D investment in key components. Supplier (manufacturer) overconfidence can harm their own profits but increase the profits of the manufacturer (supplier), and when the level of overconfidence is below a certain threshold, the damage to their own profits is less than the increase in each other's profits, thus benefiting the whole supply chain. In addition, we also find a joint effect of RS contracts and overconfidence: when the bargaining power of the supplier is low, the RS contract has a certain compensatory effect on the loss of their own profits caused by overconfidence.

These three syndromes - long covid (LC), postural orthostatic tachycardia syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) - have many symptoms in common. The common denominator remains elusive. The blood brain barrier (BBB) has been a barrier not only to microbes and toxins but also to understanding pathogenetic links. There are several areas within the brain that have no BBB. These are known as circumventricular organs (CVOs) and their location relative to CNS nuclei that direct autonomic and neuroendocrine functions is provocative in the quest for pathogenesis. In addition the majority afflicted with LC and ME/CFS appear to be those with two MTHFR polymorphisms, present in over 50% of Americans. These polymorphisms elevate homocysteine. When homocysteine is combined with CVOs, the fog of POTS and its paradox are lifted. POTS may represent the intersection of LC and ME/CFS in those with the MTHFR gene (hypermethylation or 677TT). The gut microbiomes of LC and ME/CFS, deficient in butyrates, GABA, and diversity, are then linked with MTHFR genotype 677TT. Reactivation of neurotropic EBV and VZV, due to loss of surveillance by CD4+/CD8+ T cells, is seen as secondary. The oxidative stress generated by homocysteine, loss of glutathione, low fiber diet, and persistent chronic inflammation exhaust available mitochondria and, assisted by BKN and estrogen, exacerbate all the elements of these post viral fatigue syndromes.

The purpose of this research was two-fold: (a) to observe whether highly trained adolescent swimmers abide to vitamin D supplement recommendations; and (b) to monitor changes in circulating 25-hydroxyvitamin D (25(OH)D) that occur between the autumn and winter months. Twenty swimmers (age: 17 ± 2 years) from a UK high-performance swimming club volunteered to complete two blood spot cards to determine 25(OH)D concentration: the first in an autumn training phase (October) and the second during winter training (January). All swimmers were advised to consume vitamin D3 supplements across the assessment period; however, only 50% of swimmers adhered to this recommendation. Resultantly, a winter decline in 25(OH)D was observed in non-supplementing swimmers (79.6 ± 25.2 to 52.6 ± 15.1 nmol·L-1, p = 0.005), with swimmers either displaying an ‘insufficient’ (60%) or ‘deficient’ (40%) vitamin D status. In comparison, greater maintenance of 25(OH)D occurred in supplementing swimmers (92.0 ± 25.5 to 97.2 ± 38.3 nmol·L-1, p = 0.544), although variable outcomes occurred at the individual level (four increased, three maintained, three declined). These findings highlight possible risks of vitamin D insufficiency during the winter for swimmers in the UK, possibly requiring standardised supplement practices. Moreover, alternative educational strategies may be required for swimmers to transfer knowledge to practice in order to improve supplement adherence in future.

Bioinformatics analysis of the sequences of orthologous zinc-containing peptidases of the M15_C subfamily revealed the presence of a conserved tryptophan residue near the active site, which is not involved in the formation of the protein core. Site-directed mutagenesis of this Trp114/109 residue using two representatives of the family, L-alanoyl-D-glutamate peptidases of bacteriophages T5 (Calcium-activated EndoT5) and RB49 (EndoRB49, without ion regulation) as an example, and further analysis of the 1H NMR spectra of the mutants showed that a decrease in the volume of the W → F → A residue leads to changes in the hydrophobic core and active center of the protein, and also decreased affinity for regulatory Ca2+ in the EndoT5 mutants. The inactive T5W114A mutant lacks the ability to bind the substrate. In general, the conserved Trp114/109 residue, due to the spatial restrictions of its side chain, significantly affects the formation of the catalytically active form of the enzyme and is critical for catalysis.

Background: It is assumed that the prevalence of hepatitis D in HBsAg-positive individuals reaches 4.5-13% in the world, and on average about 3% in Europe. Data from several European countries, including Slovakia, are missing or are from an older period. Methods: We analyzed all available data on hepatitis D from Slovakia, including reports from the Slovak Public Health Authority and the results of one prospective study, and three smaller surveys. The determination of anti-HDV IgG and IgM antibodies and/or HDV RNA was used to detect hepatitis D. Results: In the years 2005-2022, no confirmed case of acute or chronic HDV infection was reported in Slovakia. The presented survey includes a total of 343 patients, of which 126 were asymptomatic HBsAg carriers, 33 acute hepatitis B, and 184 chronic hepatitis B cases. In a recent prospective study of 206 HBsAg-positive patients who were completely serologically and virologically examined for hepatitis B and D, only 1 anti-HDV IgG positive and no anti-HDV IgM or HDV RNA positive cases were detected. In other smaller surveys, 2 anti-HDV IgG positive patients were found without the possibility of HDV RNA confirmation. In total, only 3 of 329 HBsAg-positive patients (0.91%) tested positive for anti-HDV IgG antibodies and none of 220 tested positive for HDV RNA. Conclusion: The available data show that Slovakia is one of the countries with a very low prevalence of HDV infection reaching less than 1% in HBsAg-positive patients. Routine testing for hepatitis D is lacking in Slovakia, and therefore it is necessary to implement testing of all HBsAg-positive individuals according to international recommendations.

Background: Hypovitaminosis D is a public health problem due to its implications for various diseases. Vitamin D has numerous functions, such as modulating the metabolism of some cellular tissues, and is expressed through the VDR gene that may influence gene expression modulation, which plays an important role in vitamin D metabolism. Objective: To evaluate the effect of the genotypes of single nucleotide polymorphism (SNP) BsmI of the vitamin D receptor (VDR) gene on VDR, SOD2, and CYP24A1 gene expression in individuals with low serum vitamin D levels. Methods: This was a cross-sectional analytical study. Individuals were invited to participate and, after signing the informed consent form, answered a structured questionnaire with identification data. Blood was collected for biochemical analysis, and vitamin D was measured by chemiluminescence; BsmI polymorphism was determined using real-time polymerase chain reaction (PCR) assays with TaqMan allelic discrimination, and gene expression was conducted by qRT-PCR using QuantiFast SYBR® Green PCR Master Mix. Data were analyzed using the SPSS 20.0 software, and differences were considered significant at p&lt;0.05. Results: 98 individuals with vitamin D ≤20 ng/dL were evaluated, and the SNP BsmI of the VDR gene showed CYP24A1 overexpression and low SOD2 expression. Conclusion: SNP Bsm I of the VDR gene can modulate the expression of the genes evaluated without interfering with serum levels.

Controlling water and food contamination by pathogenic organisms requires quick, simple, and low-cost methods. using affinity between mannose and type I fimbriae in the cell wall of Escherichia coli bacteria as evaluation elements compared to the conventional plate counting technique enables a reliable sensing platform for the detection of bacteria. In this study, a simple new sensor based on electrochemical impedance spectroscopy (EIS) for rapid and sensitive detection of Escherichia coli was developed. Biorecognition layer of the sensor was formed by covalent attachment of p-carboxyphenylamino mannose (PCAM) to gold nanoparticles (AuNPs) electrodeposited on the surface of glassy carbon electrode (GCE). The resultant structure of PCAM was characterized and confirmed using FTIR. The developed biosensor demonstrated a linear response with a logarithm of bacterial concentration (R2 = 0.998) in the range of 1.3 × 10 1~ 1.3 × 106 CFU.mL−1with the limit of detection of 2 CFU.mL−1 within 60 min. The sensor did not generate any significant signals with two non-target strains, demonstrating high selectivity of the developed biorecognition chemistry. Selectivity of the sensor and its applicability to analysis of the real samples was investigated in samples of tap water. Overall, the developed sensor has shown to be promising for the detection of E. coli pathogen in water due to its high sensitivity, short detection time, low cost, high specificity, and user-friendliness.

Ultraviolet (UV) radiation has both harmful and beneficial effects on human health. It can cause skin damage and cancer, but also provides the primary source of vitamin D. Additionally, UV radiation affects energy metabolism in mice with metabolic diseases and has protective effects on hypertension and cardiovascular diseases.Metabolic Syndrome is a collection of metabolic dysfunctions such as dyslipidemia, hypertension, hyperglycemia, abdominal/central obesity, and insulin resistance. Chronic UVR exposure suppressed obesity and type 2 diabetes in high-fat diet-fed mice, while vitamin D supplementation did not replicate these effects. On the other hand, topical application of nitric oxide (NO) donors replicated UV effects on mice, and NO scavengers prevented the positive impact of UV. UVR may prevent the development of obesity and metabolic syndrome through mechanisms that depend on UVR-induced NO, not vitamin D. Exposure to sunshine has a protective impact on blood pressure and cardiovascular disease. Although lower vitamin D concentration is linked to increased hypertension and the incidence of CVD, oral vitamin D supplementation does not decrease blood pressure or the risk of CVD, indicating that vitamin D may not mediate the beneficial effects of sun exposure. Instead, NO plays a crucial role as an endogenous vasodilator, produced by the vascular endothelium. Solar UVA may release nitrogen oxides from skin storage into the bloodstream, lowering blood pressure and cardiovascular mortality.In conclusion, UVR exposure could be a promising non-pharmacological intervention for metabolic syndrome, hypertension, and CVD prevention, and NO may play a crucial role in mediating these effects. Further research is needed to explore the precise mechanisms and identify the optimal doses and exposure times of UVR.

Relapses and resistance to therapeutic agents are major barriers for treatment of acute myeloid leukemia (AML) patients. This unfavorable circumstance emphasizes the need for new strategies targeting drug-resistant cells. As IDH mutation is present in the preleukemic stem cells and systematically conserved at relapse, targeting mutant IDH cells would be essential to achieve a long-term remission in the AML subgroup with IDH mutation. Here, using a panel of human AML cell lines and primary AML patient specimens harboring IDH mutation, we showed that the presence of IDH mutation through the production of an oncometabolite (R)-2-HG induces vitamin D receptor related transcriptional programs, priming these AML cells to differentiate with pharmacological doses of ATRA or/and VD. This activation occurs in a CEBP-dependent manner. Accordingly, our findings illuminate potent and cooperative effects of IDH mutation and vitamin D pathway to differentiate in AML, revealing a novel therapeutic approach easily transferable/immediately applicable in clinics for this subgroup of AML patients.

Appropriate supplementation of vitamin D can affect infections, allergy, and mental and behavioral development. This study aimed to assess the effectiveness of monitored vitamin D supplementation in a population of preterm infants. 109 preterm infants (24 0/7–32 6/7 weeks of gestation) were randomized to receive 500 IU vitamin D standard therapy (n=55; approximately 800-1000 IU from combined sources) or monitored therapy (n=54; with an option of dose modification). 25(OH)D concentrations were measured at birth, 4 weeks of age, and 35, 40, and 52±2 weeks of post-conceptional age (PCA). Vitamin D supplementation was discontinued in 23% of infants subjected to standard treatment due to increased potentially toxic 25(OH)D concentrations (&gt;90 ng/mL) at 40 weeks of PCA. A significantly higher infants’ percentage in the monitored group had safe vitamin D levels (20–80 ng/mL) at 52 weeks of PCA (p=0.017). We observed increased vitamin D levels and abnormal ultrasound findings in five infants. Biochemical markers of vitamin D toxicity were observed in two patients at 52 weeks of PCA in the control group. Inadequate and excessive amounts of vitamin D can lead to serious health problems. Supplementation with 800–1000 IU of vitamin D prevents deficiency and should be monitored to avoid overdose.

Abstract: COVID-19 in 2020 brought challenges to the Brazilian public health system with an emerging virus with respiratory contagion called SARS-CoV-2. There are few studies in Brazil and in some countries, on the increased incidence of certain viral respiratory infections, includ-ing H1N1 and coronavirus and their association with low levels of vitamin D, zinc and iron. The aim of this study was to demonstrate that the deficit of vitamin D, zinc and iron has an impact on the infectious process of patients with COVID-19 and to establish new forms of prevention for the worsening of COVID-19 in the human body. Data were collected from medical records and test results from patients being followed up during the treatment period for COVID-19. Patients with low blood levels of vitamin D, zinc and iron during the treatment period of COVID-19 had a higher percentage of worsening and complications requiring hospitalization in intensive care beds. The ingestion of vitamin D, zinc and iron in the treatment period of patients with COVID-19 in addition to being an immunological protector against SARS-CoV-2 and alleviating the process of worsening the disease can also act as a biomarker in cases of this disease.

Background Bangladesh has been attracting international students on various subjects in recent times. Every year students from different parts of the world come to study undergraduate and postgraduate courses, mostly at private universities in Bangladesh. This study evaluates the depression status among international students who are studying dentistry in Bangladesh. Methods This cross-sectional survey was conducted among International undergraduate dental students who enrolled in the Bachelor of Dental Surgery program in nine public and private dental colleges in Bangladesh. A total of 206 students completed the survey, and CES-D 10 items Likert scale questionnaire was used for data collection. The Cronbach alpha for CES-D 10 scale items for this population is 0.812. Results The majority of the students (79.5%) are below 24 years of age, and students who cannot communicate well in Bengali (Bangla), about 60% of them have experienced depression. About 77.3% (p< 0.00) of the international students having financial difficulties exhibited depression. The international students who went through financial problems were two times more likely to suffer from depression (OR=2.38; p-value <0.01). Conclusion This study tried to highlight the struggles faced by international students in Bangladesh studying dentistry. It is evident from the findings that several factors influence students' mental well-being during demanding dental education years.

Studies shows that, normal to high serum 25(OH)D status appears to have some beneficial influence on the incidence and severity of some, though not all, types of infections. However, studies with vitamin D supplementation on young children produced conflicting results with respect to the level of vitamin D deficiency among common medical illnesses among children. Method: A systematic review of literatures from PubMed, CINAHL, Web of science, global health and Google scholar electronic databases was conducted to assess the pooled prevalence of vitamin D deficiency among healthy and sick children in sub-Saharan Africa. The data was extracted by two authors independently using standard data extraction format and STATA Version 14 was used for analysis. The heterogeneity of the studies was assessed by using I2 test. A random-effects model was used to estimate the pooled prevalence among both healthy and sick children. Presence of publication bias was checked using Funnel plot and Egger's test. Result: A total of 1212 articles were identified by the total search of utilized data bases of which 13 papers fulfilled the inclusion criteria and accessible with full document. The meta-analysis revealed that the pooled prevalence of vitamin D deficiency among healthy children in this study was 50.06% (95%CI 33.46%, 66.67%) with mean serum vitamin D level of 41.06 nm/L (CI range from 23.82nm/L to 58.31nm/L). The pooled prevalence among the sick children was 39.36% (CI 20.57%, 57.96%) with 66.96nm/L (95% CI 54.81nm/L, 79.11nm/L) mean concentration of vitamin D. Comparing the two level of the pooled prevalence, the prevalence among the healthy children was significantly higher compared to those who have common medical illnesses and the pooled mean concentration among the sick was much higher than the mean concentration among healthy children. Conclusion: The level of pooled prevalence among both group of population was significantly of public health concern and the prevalence among the healthy children was much higher among the sick children implying the need for reconsideration of available recommendations for the prevention of vitamin D deficiency

Background & Aims: The covid19 is a world changing challenge. Furthermore, this disease challenges our capacities to change our point of view in the domain of infectiology, immunology and global public health. Many trials try some drug such as antiviral (lopinavir, remdesivir) interferon, and the chloroquine. Unfortunately, all approach is not really convincing at this time. We are proposing another approach on this issue. In infectiology there are two protagonists : the host and its immune system versus pathogens and its virulence. Our approach focuses on an intervention on the host’s immune system and how stimulate and modulate its reactions. Methods: We searched on PubMed and Google Scholar databases for French and English-language studies, without a limit of date of publications, for randomized clinical trials, meta-analyses, reviews, systematic reviews, observational studies, case report. We performed a review on the field of immunology enhancements by nutrients use. Results: We identified groups of vitamins (D and C), oligo-elements (magnesium, zinc, selenium) and nutrition advice which enhance immune system response. Indeed, these supplements have some proved properties in modulating and stimulating the immune system. For example, a recent study demonstrates that vitamin D deficiency is linked with the severity of covid19. Majority of the population has a deficiency in these elements. According to this, we propose a therapeutic protocol using these elements to reach an efficient therapy against covid19 by enhancing host’s immune system. Conclusion: Due to this serious pandemic, any solutions must not be disregarded. The nutrition way is an entire part of the solution.

The impact of nutrition on immunity is an intense area of research. Malnutrition is linked to a higher risk of microbial infections, while severe infections usually lead to a nutritional imbalance in affected patients. The nutritional status has an impact on the severity of the ongoing SARS-CoV-2 infection. Studies conducted on small numbers of patients have shown the benefits of maintaining optimal vitamin (B12 and D) and mineral (zinc and magnesium) balance in reducing the intensity of COVID-19. Although consuming a balanced diet with a healthy lifestyle is always desirable, the importance of such practice is even more meaningful during the COVID-19 pandemic. Keeping an optimal balance of vitamins and minerals through healthy dietary habits helps to maintain a robust immune system that is essential to combat invading microbial pathogens, including SARS-CoV-2.

On the primitive Earth, both L- and D-amino acids would have been present. However, only L-amino acids are essential blocks to construct proteins in modern life. To study the relative stability of D-amino acid substituted peptides, a variety of computational methods were applied. Ten prebiotic amino acids (Gly, Ala, Asp, Glu, Ile, Leu, Pro, Ser, Thr, and Val) were previously determined by multiple meteorite, spark discharge, and hydrothermal vent studies. Some previously reported early Earth polypeptide analogs were focused on in this study. Tripeptides composed of only Asp, Ser, and Val exemplified that different positions (i.e., N-terminus, C-terminus, and middle) made a difference in the minimal folding energy of peptides, while the chemical classification of amino acid (hydrophobic, acidic, or hydroxylic) did not show a significant difference. Hierarchical cluster analysis for dipeptides with all possible combinations of the proposed ten prebiotic amino acids and their D-amino acid substituted derivatives generated five clusters. Primordial simple polypeptides were modeled to test the significance of molecular fluctuations, secondary structure occupancies, and folding energy differences based on these clusters. We found peptides with α-helices, long β-sheets, and long loops are usually less sensitive to D-amino acid replacements in comparison to short β-sheets. Intriguingly, amongst 129 D-amino acid residues, mutation sensitivity profiles presented that the ratio of more to less stable residues was about 1. In conclusion, some combinations of a mixture of L- and D-amino acids can potentially act as essential building blocks of life.

Background: Diabetic retinopathy (DR) is one of the most prominent pathological microvascular complications in diabetes. A series of studies reported that vitamin D deficiency was associated with increased prevalence of retinopathy in diabetic patients but the results were inconsistent. In this study we focused on evaluating the relationship between vitamin D deficiency and DR by conducting a meta-analysis of observational studies. Methods: Systematic computerized searches were performed in PubMed, MEDLINE, and the Cochrane Library for relevant original articles till November 20, 2016. The pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated to assess the associated value of vitamin D deficiency to the risk of DR. 9 studies including 6332 participants were subjected to final analysis. Results: The results indicated that vitamin D deficiency increases the risk of DR (OR = 1.57, 95% CI 1.32-1.87) with a little heterogeneity (I2 = 23%). In addition, the subgroup analysis demonstrated that there were obvious heterogeneities in T2DM (I2 = 47.8%). Sensitivity analysis showed that the results were relatively stable and reliable. Conclusion: our meta-analysis demonstrated that vitamin D deficiency could increase the risk of DR.

Origins of the time, mass, electric charges and magnetic monopoles are explained. The energies, electric charges and magnetic charges of the particles are defined as E = cDtDV and |q| = cDt = E/DV, and |q_m| = c²Dt, respectively, for the 3-D quantized spaces warped along the time axis direction of ct in the 4-D Euclidean space. The energy (or mass) and charges (or electric charges and magnetic charges) are the vectors along the time axis of ct in the 4-D Euclidean space. This new concept is closely connected to the wave function of the quantum mechanics. The electric charges, magnetic charges and energies have the property of the space direction independence. Magnetic monopoles (charges) are the force carrying bosons with the inside electric field time loop. Electric monopoles are the elementary fermions. Photon space fluctuations are explained with the quantized magnetic charges.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women, characterized by fluid-filled sacs in the ovaries and various symptoms including high androgen levels, endometrial irregularities, and cysts. While the cause of PCOS is unknown, it has been linked to genetic, endocrine, and metabolic factors, and there are several treatment options, including lifestyle modifications, medications, and surgery. Natural products, such as medicinal plants and fruits, are being explored as potential treatments for PCOS due to their bioactive compounds with pharmacological effects related to antioxidant, antimicrobial, anticancer, and antidiabetic properties. Some of these compounds improve insulin sensitivity, reduce inflammation, and enhance glucose metabolism, which is beneficial for women with PCOS. This review examined the effects of natural products on PCOS, including their effects on ovarian histological changes, blood glucose, sex hormones, and lipid profile, based on animal and human studies. This study suggests that the use of natural products as complementary medicine can be a promising resource for the development of effective therapeutics for PCOS, but that further research is needed to fully understand their benefits

As an option to deal with the insulin-dependent disease, a recent commuted PD control strategy is designed and carefully analyzed for different clinic diabetic patients. This controller approach is mainly conceived to stabilize the glucose blood concentration in a diabetic patient around its basal value, hence avoiding extreme situations such as hypoglycemia and hyperglycemia. This control strategy receives two inputs carefully tuned to actuate when the measured variable is out of a prescribed healthy zone. Therefore, one of these variables is invoked to decrease the glucose concentration to insulin injection, and the other is employed to increase the glucose absorption, both by using a proper PD controller. According to our numerical experiments, our controller approach performs well, even when there is an external disturbance in the controlled system.

The objective of this pilot study was to compare glucose concentrations in capillary blood (CB) samples analysed in a laboratory by a validated method and glucose concentrations measured in the interstitial fluid (ISF) by continuous glucose monitoring under different physical activity levels in a postprandial state in healthy and active subjects without diabetes. Ten healthy, active subjects (26±4 years, 67±11 kg bodyweight (BW), 11±3 h) were included in the study. Within 14 days, they underwent six tests consisting of a) resting fasted (R/Fast), b) resting after intake of 1 g glucose/kg BW (R/Glc) and c) running for 60 minutes at moderate (65/Glc) and d) high (85/Glc) intensity after intake of 1 g glucose/kg BW. Data were collected in the morning, following a standardised dinner before test day. Sensor-based glucose concentrations were compared to simultaneous capillary blood glucose concentrations. Pearson’s r correlation coefficient was highest for R/Glc (.92, p<.001) compared to R/Fast (.45, p<.001), 65/Glc (.60, p<.001) and 85/Glc (.70, p<.001). Mean absolute relative deviation (MARD) and standard deviation (SD) was smallest for resting fasted and similar between all other conditions (R/Fast: 8±6%, R/Glc: 17±12%, 65/Glc: 22 ± 24%, 85/Glc: 18±17%). However, Bland-Altman plot analysis showed a higher range between lower and upper limits of agreement (95% confidence interval) of paired data under exercising compared to resting conditions. Under resting fasted conditions, both methods produce similar outcomes. Under resting postprandial and exercising conditions, respectively, there are differences between both methods. However, further data in healthy subjects need to be gathered considering physical activity and nutrition status.

The kidney and the heart work together in balancing the body circulation and although their physiology is based on strict inter dependence, their performance fulfills different aims. While the heart can rapidly increase its own oxygen consumption to comply with the wide changes in metabolic demand linked to body function, the kidney physiology is primarily designed to maintain a stable metabolic rate and has limited capacity to cope with any steep increase in renal metabolism. In the kidneys the glomerular population filters a large amount of blood and the tubular system has been programmed to reabsorb 99% of filtrate by reabsorbing sodium together with other filtered substances including all glucose molecules. Glucose reabsorption involves the sodium-glucose cotransporters SGLT2 and SGLT1 on the apical membrane in the proximal tubular section; it also enhances bicarbonate formation so as to preserve the acid-base balance. The complex work of reabsorption in the kidney is the main factor in renal oxygen consumption; analysis of renal glucose transport in disease states is providing better understanding of the renal physiology changes that occur when clinical conditions alter the neurohormonal response leading to an increase in glomerular filtration pressure. In this circumstance glomerular hyperfiltration occurs, imposing a higher metabolic demand on kidney physiology and causing progressive renal impairment. Albumin urination is the warning signal of renal engagement over-exertion and most frequently heralds heart failure development, regardless of disease etiology. The review analyzes the mechanisms linked to renal oxygen consumption, focusing on sodium-glucose management.

Mammals have two insulin-like growth factors (IGF) that are key mediators of somatic growth, of tissue differentiation and cellular responses to stress. Thus, the mechanisms that regulate the bioavailability of IGFs are important in both normal and aberrant development. IGF-I levels are primarily controlled via the growth hormone-IGF axis, in response to nutritional status, and also reflect metabolic diseases and cancer. One mechanism that controls IGF bioavailablity is the binding of circulating IGF to a number of binding proteins that keep IGF in a stable, but receptor non-binding state. But even before IGF is released from the cells that produce it, it undergoes an obligatory association with a ubiquitous chaperone protein, GRP94. This binding is required for secretion of a properly folded, mature IGF. This chapter reviews the known aspects of the interaction and highlights the specificity issues yet to be determined. The IGF-GRP94 interaction provides a potential novel mechanism of idiopathic short stature, involving the obligatory chaperone and not just IGF gene expression. It also provides a novel target for cancer treatment, as GRP94 activity can be either inhibited or enhanced.

This study explored the effects of a comprehensive health care program (CHCP) on blood pressure, blood glucose, body composition, and depression in older adults living alone. We used a quasi-experimental, two-group, pre-posttest design. The CHCP consisted of open lectures, health counseling, exercise classes, nutrition counseling, and self-help group meetings at a local senior welfare center. Fifty-eight subjects participated in this study, with thirty subjects in the experimental group and twenty-eight subjects in the control group. Data were analyzed using the descriptive statistics, χ²-test, and t-test. Comparisons of the pretest and posttest systolic blood pressure (t = - 2.530, p < .016) and blood glucose (t = 3.089, p < .004) between the experimental and control groups showed significant differences. In both the experimental (t = 3.949, p < .001) and control groups (t = 3.816, p < .002), depression symptoms showed a significant decrease post-test, compared with pre-test. Our findings infer that older adults require physical and psychosocial healthcare and that more efforts must be made to improve the general health and wellbeing of this population group.

In this work, an enzymatic sensor, based on a bionanocomposite film consisting of a polyelectrolyte complex (PEC) [Chitosan/kappa-carrageenan] doped with gold nanoparticles (AuNPs) encapsulating glucose oxidase (GOD) deposited on a gold electrode (Au) for glucose sensing, is described. Using the electrocatalytic synergy of AuNPs and GOD as a model of enzyme, the variation of the current (µA) as a function of the log of the glucose concentration (log [glucose]), shows 3 times higher sensitivity for the modified electrode (283.9) compared to that of the PEC/GOD modified electrode (93.7), with a detection limit of about 5 µM and a linearity range between 10µM and 7mM. The response of the PEC/AuNPs/GOD based biosensor also presents good reproducibility, stability and negligible interfering effects from ascorbic acid, uric acid, urea and creatinine. The applicability of the PEC/AuNPs/GOD based biosensor was tested in glucose-spiked saliva samples and acceptable recovery rates were obtained.

Diabetic patients need long-term and frequent glucose monitoring to assist in insulin intake. The current finger-prick devices are painful and costly which make noninvasive glucose sensors highly demanded. In this review paper, we discuss several advanced electromagnetic (EM) wave based technologies for noninvasive glucose measurement, including infrared (IR) spectroscopy, photoacoustic (PA) spectroscopy, Raman spectroscopy, fluorescence, optical coherent tomography (OCT) and microwave sensing. Development and progress of each method are discussed regarding fundamental principle, system setup and experimental results. Despite the promising achievements reported previously, there is no established product to obtain FDA approval or survive marketing test. Limitations and prospects of these techniques are discussed at the end of this review.

A cuprous oxide (Cu₂O) thin layer served as the base for a non-enzymatic glucose sensor in an alkaline medium, 0.1 NaOH solution, with a linear range of 50-200 mg/dL using differential pulse voltammetry (DPV) measurement. An X-ray photoelectron spectroscopy (XPS) study confirmed the formation of the cuprous oxide layer on the thin gold film sensor prototype. Quantitative detection of glucose in both phosphate-buffered saline (PBS) and undiluted human serum were carried out. Neither ascorbic acid nor uric acid even at a relatively high concentration level of 100mg/dL in serum interfered with the glucose detection, demonstrating the excellent selectivity of this non-enzymatic cuprous oxide thin layer based glucose sensor. Chronoamperometry (CA) and single potential amperometric voltammetry were used to verify the measurements obtained by differential pulse voltammetry (DPV), and the positive results validated that the detection of glucose in a 0.1 M NaOH alkaline medium by DPV measurement was effective. Nickel, platinum and copper are commonly used metals for non-enzymatic glucose detection. The performance of these metal-based sensors for glucose detection using DPV were also evaluated. Cuprous oxide (Cu₂O) thin layer based sensor showed the best sensitivity for glucose detection among the sensors evaluated.

The cause of sarcoidosis is unknown, and vitamin D is contraindicated to treat the condition. We therefore ask what causes sarcoidosis and why vitamin D can be dangerous for those so afflicted. We propose a contrary hypothesis: sarcoidosis is a physiological process of defense against cancer that requires the substrate vitamin D. We tested this hypothesis, finding many case reports involving sarcoidosis and cancer—further cases of cancer mimicry by sarcoidosis. Several reports describe spontaneous healing of cancer in the presence of sarcoidosis. In the context of the granulomas of sarcoidosis, monocytes are the site of vitamin D release. Furthermore, active vitamin D can control cancer cells by using the vitamin D receptors of the nucleus. That granulomas consistently do not caseate is explained as a confrontation with human molecules and the cancer cells’ complete absorption. The striking fact that granulomas of sarcoidosis mostly lack cancerous cells is interpreted as a result of a well-functioning sarcoidosis process. We view the typical sarcoidosis monocytic synthesis of active vitamin D as a successful defense against cancer: a theory we call the “endogenous program organizing cancer apoptosis” (EPOCA).

This paper introduces PatchFusion, an innovative approach for nonrigid tracking and reconstruction of deformable objects using a single RGB-D sensor. Existing methods face challenges in accurately capturing the rapid deformations of soft and flexible objects, thereby limiting their utility in diverse scenarios. Our approach overcomes this challenge by employing a dynamic patch-based framework that adapts to rapid inter-frame motions. Firstly, patch-wise rigid transformation fields for non-overlapping patches are solved via Iterative Closest Point (ICP) by incorporating geometric features as additional similarity constraints, thereby enhancing robustness and accuracy. Secondly, deformation optimization based on a nonrigid solver is applied to refine the coarse transformation fields. In order to enable simultaneous tracking and reconstruction of deformable objects, the patch-based rigid solver is designed to run in parallel with the nonrigid solver, serving as a plug-and-play module requiring minimal modifications for integration while enabling real-time performance. Following a comprehensive evaluation, PatchFusion showcases superior performance in effectively dealing with rapid inter-frame deformations when compared to existing techniques, rendering it a promising solution with broad applicability across domains such as robotics, computer vision, and human-computer interaction.

The global population is at risk of vitamin D deficiency due to low exposure to sunlight and low intake of the vitamin through diet. The aim was to investigate in women the association between vitamin D status and parathyroid hormone (PTH), ultraviolet radiation, lifestyle, ethnicity, social conditions, and residential greenness. A 1-year longitudinal study assessed vitamin D status in 309 women, latitude 51° 14' N. Blood samples were taken four times throughout the year for analysis of 25(OH)D and serum PTH concentration. After each seasonal visit, the individuals completed 4-day diet diaries and used two dosimeter badges for 1 week to estimate weekly UVR exposure. A questionnaire was applied to provide information about lifestyle and their ethnicity. Residential greenness was measured by Normalized Difference Vegetation Index (NDVI), within a 1000 m radius around each participant’s home address. Women living in greener spaces were more likely to have improved vitamin D status (RR: 1.51; 95%CI: 1.13 – 2.02), as well as those who were more exposed to UVR (RR: 2.05; 95%CI: 1.44 – 2.92). Our results provided a first insight into the connection between vitamin D, residential greenness, and lifestyle in a region of temperate climate and with a high degree of urbanization.

This study aims to analyse whether Chinese companies' R&amp;D investment affects management innovation performance. Also, this dissertation defines management innovation as diversification strategies such as technology and industry diversification and analyzes the impact of these diversification strategies. In particular, this paper analyzes whether R&amp;D investment leads to technology and industry diversification and whether technology diversification creates a mediating effect in the process of R&amp;D investment leading to industry diversification. The analysis results can be summarized as follows: First, R&amp;D investment showed a significant positive relationship with industry diversification. Second, R&amp;D investment shows a significantly positive relationship with technology diversification. Third, technology and industry diversification showed a positive relationship. Fourth, this study examined the mediating role of technology diversification, and it was confirmed that technology diversification plays a mediating role in the effect of R&amp;D investment on industry diversification. R&amp;D investment and business innovation play a key role in the sustainable development of enterprises, and the findings of this paper have important reference value for enterprises' R&amp;D investment decision-making. The results of this study provide the following implications that Chinese companies improve business innovation performance by increasing their R&amp;D investment, promoting innovative R&amp;D, and improving technology diversification and industry diversification strategies.

Cassava mosaic disease (CMD) and cassava brown streak disease (CBSD) are endemic threats to cassava production. To fill the existing gaps in the understanding of the epidemiology of these diseases in Côte d’Ivoire, nationwide field surveys were conducted in 2016, 2017 and 2020. The leaf samples collected were analysed by PCR. CBSD was not detected in all fields visited. However, an increase of CMD incidence was observed from 45.95% in 2016 to 51.37% in 2020 while CMD severity remained moderate over the years with a mean value of 2.29. Low whiteflies number was observed in field and decreasing over the years. Molecular analysis allowed detection of East African cassava mosaic Cameroon virus (EACMCMV) in single as well as in mixed infection with African cassava mosaic virus (ACMV). Single EACMCMV infection, which was detected only in three agroecological zones of the eastern Côte d’Ivoire in 2016, spread throughout the country in 2017 and became more widespread in 2020 with a preponderance in the central and southern zones, whereas the ACMV+EACMCMV coinfection has spread to the entire zones studied. Knowing the dynamics of the evolution of these viruses across the country, better disease management strategies could be adopted to control the disease.

This review examines the challenges faced by the pig industry, with a specific emphasis on improving the health and growth of weaned pigs. It emphasises the immediate necessity of investigating alternative approaches to managing pig nutrition and health due to restrictions on the use of antibiotics and the prohibition of zinc oxide in weaned pig diets. The weaning phase is identified as a critical stage in piglet development, characterized by stressors that affect their gastrointestinal health, immune responses, and overall physiology. The primary challenge during weaning arises from transitioning piglets from a digestible milk-based diet to a less digestible cereal-based feed, causing nutritional stress. This manifests as reduced feed intake, leading to gastrointestinal disturbances, intestinal inflammation, and adverse effects on intestinal structure and microbiota. To address these challenges and optimise piglet development, various nutritional strategies have been explored. Notably, glucans, particularly β-glucans from fungi, cereals, algae, and yeast, show promise in alleviating weaning-related issues. Furthermore, it's important to highlight the critical roles played by vitamin D and selenium in piglet nutrition. These essential nutrients can be sourced naturally from enriched mushrooms that are specifically enriched with vitamin D and selenium, providing a valuable dietary option. In conclusion, effective nutritional strategies, including glucans, vitamin D, selenium, and enriched mushrooms, are beneficial for addressing weaning-related challenges.

Limited studies have shown that exposure to arsenic is associated with serum vitamin D levels, but the results are still inconsistent. A cross-sectional study of 762 participants was conducted in Wenshui Country, Shanxi Province, which was identified as an area of water-borne arsenicosis. The results showed positive relationship between arsenic species (iAs, MMA, DMA) and serum 25(OH)D. Binary logistic regression analysis showed that the significant increases of 0.4% and 0.6% in the risk of vitamin D excess for every 1-unit increment in the Box-Cox transformed urinary tAs and DMA, respectively. After stratifying populations based on arsenic methylation metabolic capacity, each one-unit increase in the Box-Cox transformed tAs level was associated with increases of 0.064 (95%CI: 0.032 to 0.096) in serum 25(OH)D in the populations with iAs% above the median. In the populations with skin hyperkeratosis, urinary iAs was positively associated with serum 25(OH)D (β=0.592, 95%CI: 0.041 to 1.143). Overall, our findings support the positive relationship between urinary arsenic and serum 25(OH)D.

Type 1 diabetes (T1D) is one of the most prevalent endocrinological diseases among children and young adults, with a growing incidence rate reaching up to 2.9 new cases per year per 100 000 persons below 15 years of age. We report the rare case of a 20-year-old female patient with T1D, hemoglobin D (HbD) heterozygote variant and high myopia of -10,00 spheric diopters and describe the retinal microvascular alterations visible on OCT angiography (angio-OCT). The patient also presented severe stature deficit (less than 3 standard deviations) and delayed puberty, which could not be explained only by suboptimal glycemic control, indicated a possible hypopituitarism. The HbA1c level evaluated with high performance liquid chromatography (HPLC) method was 6.5%, a falsely low value due to the HbD hemoglobinopathy. On ophthalmic evaluation the angio-OCT scan showed the following retinal microvascular alterations for the RE: the FAZ area vas 0.39 mm2, the FAZ perimeter was 2.88 mm and the circularity index was 0.58; for the LE: the FAZ area vas 0.34 mm2, the FAZ perimeter was 3.21 mm and the circularity index was 0.41. Clinicians should consider high performance retinal screening methods such angio-OCT evaluation for young T1D patients, especially for those with associated pathologies like high myopia and hemoglobinopathies. Moreover, multiple evaluation methods of the HbA1c values are mandatory as hemoglobinopathies can interfere with HbA1c assay methods accuracy.

Asthma is a common chronic respiratory disease that affects millions of people worldwide, and its prevalence continues to increase. Vitamin D has been proposed as a potential environmental factor in asthma pathogenesis, due to its immunomodulatory effects. This systematic review aimed to evaluate the effect of vitamin D supplementation on airway remodeling in asthma. We conducted a comprehensive search of electronic databases and identified experimental studies and randomized controlled trials that investigated the impact of vitamin D supplementation on airway remodeling in asthma. The studies included in this review suggest that vitamin D inhibits airway smooth muscle cell contraction and remodeling, reduces inflammation, and regulates collagen synthesis in the airways, and modulates the action of bronchial fibroblasts. However, one study suggests that TGF-β1 can impair vitamin D-induced and constitutive airway epithelial host defense mechanisms. Overall, vitamin D appears to influence many of the pathways central to asthma progression, indicating a promising potential in asthma management and prevenation of asthma progression.

Ketamine is a dissociative anesthetic and antidepressant with several biological targets. Among the many targets, ketamine, notably, has an antagonistic effect on molecular N-methyl-D-aspartate (NMDA) receptors and has been identified as a non-competitive inhibitor of these receptors. Although ketamine has a wide range of therapeutic uses in the clinical setting, it is often used recreationally due to its psychoactive and analgesic effects. Regardless of the indication, prenatal exposure to ketamine has been widely investigated. The misuse of this drug, particularly in pregnant women, has been a point of concern. The neurotoxic potential of ketamine positions it as a danger to a developing fetus. Furthermore, the ability of ketamine to cross the blood-placental barrier poses a threat to the health and maturation processes of the neonate. This paper reviewed published work that explores the mechanisms through which prenatal ketamine exposure can cause altered neurodevelopment, neurobehavior, and the physiological consequences that follow. By exploring investigations using multiple different subjects such as: rodents, non-human primates, and human subjects, this paper develops a full picture of the existing data to generate a strong foundation for improved and informed public health policies.

Background: the nature of alpha-D-mannose - natural aldohexose sugar, C-2 glucose epimer, whose intended use is for preventing urinary tract infections - in the interaction with E. coli is addressed in order to drive the issue of its regulatory classification as a medicinal product or medical device. Methods: PRISMA systematic review approach was applied; Delphi Panel method used to target consensus on statements retrieved from evidence. Results: Based of regulatory definitions and research evidences, the mechanism of D-mannose does not involve a metabolic or immunological action while there is an uncertainty regarding the pharmacological action. Specific interaction between the product and the bacteria within the body occurs, but its nature is inert: it does not induce a direct response activating or inhibiting body processes. Moreover, the action of D-mannose takes place, even if inside the bladder, outside the epithelium on bacteria that have not yet invaded the urothelial tissue. Therefore, its mechanism of action is not directed to host structures but to structures (bacteria) external to the host's tissues. Conclusions: From a regulatory perspective, D-mannose maintains the current medical device classification: new regulations and legal judgments can add further considerations. From a pharmacological perspective, research is driven versus synthetic mannosides: no further considerations are expected on alpha-D-mannose.

To characterize the metabolic actions of D-Pinitol, a dietary inositol, in male Wistar rats, we analysed its oral pharmacokinetics and its effects on a) the secretion of hormones regulating metabolism (insulin, glucagon, IGF-1, ghrelin, leptin and adiponectin), b) insulin signaling in the liver and c) the expression of glycolytic and neoglucogenesis enzymes. Oral D-Pinitol administration (100 or 500 mg/Kg) resulted in its rapid absorption and distribution to plasma and liver compartments. Its administration reduced insulinemia and HOMA-IR, while maintaining glycaemia thanks to increased glucagon activity. In the liver, D-Pinitol reduced the key glycolytic enzyme pyruvate kinase and decreased the phosphorylation of the enzymes AKT and GSK-3. These observations were associate with an increase in ghrelin concentrations, a known inhibitor of insulin secretion. The profile of D-Pinitol suggests its potential use as a pancreatic protector decreasing insulin secretion through ghrelin upregulation while sustaining glycaemia through liver-based mechanisms of glycolysis control.

Elevated blood glucose levels, known as glycemia, play a significant role in sudden cardiac arrest, often resulting in sudden cardiac death, particularly among those with diabetes. Understanding this link has been a challenge for healthcare professionals, leading many research groups to investigate the relationship between blood glucose levels and cardiac electrical activity. Our hypothesis suggests that glucose-sensing mechanisms in cardiac tissue could clarify this connection. To explore this, we adapted a single-compartment, in-silico model of the human atrial node's action potential. We incorporated glucose-sensing mechanisms with voltage-gated sodium ion channels using ordinary differential equations. Parameters for the model were based on existing experimental studies to mimic the impact of glucose levels on atrial node action potential firing. Simulations using voltage clamp and current clamp techniques showed that elevated glucose levels decreased sodium ion channel currents, leading to a reduction in the sinoatrial node action potential frequency. In summary, our model provides a cellular-level understanding of how high glucose levels can lead to bradycardia and sudden cardiac death.

Heat-stressed lactating dairy cattle exhibit unique metabolic symptoms; many of which are undoubtedly involved in heat-induced subfertility. Because of its known systemic effects, we hypothesized that γ-aminobutyric acid (GABA) participates in the regulation of insulin and progesterone during heat stress. Multiparous lactating Holstein cows (n=6) were studied during four experimental periods: 1) thermoneutral (TN; d 1-5), 2) TN + hyperinsulinemic-hypoglycemic clamp (d 6-10), 3) heat stress (HS; d 16-20), and 4) HS + euglycemic clamp (d 21-25). Blood samples were collected once daily via coccygeal venipuncture into heparinized evacuated tubes. Analysis of GABA concentrations from all four treatment periods yielded no differences. In direct comparison to TN concentrations, plasma GABA tended to be decreased during HS (16.57±2.64 vs 13.87±2.28 ng/ml, respectively, P = 0.06). Both milk production and plasma insulin were moderately correlated with plasma GABA (r=0.35, P<0.01; r = -0.32, P<0.01). Plasma progesterone was correlated with plasma GABA concentrations during TN but not HS. These results are the first to indicate that peripheral GABA could be involved in regulating aspects of production and reproduction during heat stress. More research is needed to determine its precise role(s).

A key response to glucose stress is an increased production of unsaturated fatty acids to balance the increase of saturated fatty acids in the membrane. The C. elegans homolog of stearoyl-CoA desaturase, FAT-7, introduces the first double bond into saturated C18 fatty acids yielding oleic acid and is a critical regulatory point for surviving cold and glucose stress. Here, we incorporated 13C stable isotopes into the diet of nematodes and quantified the 13C-labelled fatty acid by GC-MS and HPLC/MS-MS to track the metabolic response to various concentrations of glucose. Previous work has analyzed membrane composition of C. elegans when responding to mild glucose stress and showed few alterations in overall fatty acid composition in the membrane. Here, in nematodes exposed to higher concentrations of glucose, a specific reduction of oleic acid and linoleic acid was observed. Using time courses and stable isotope tracing, the response of fatty acid me-tabolism to increasing levels of glucose stress has been characterized, revealing a funneling of monounsaturated fatty acids to preserve polyunsaturated fatty acid abundance. Taken together, higher levels of glucose unveil a specific reduction of oleic and linolenic acid in the metabolic re-wiring required to survive glucose stress.

Sulfite and kraft pulping are two principal methods of industrial delignification of wood. In recent decades, those have been considered as possibilities to pretreat recalcitrant wood lignocellulosics for enzymatic hydrolysis of polysaccharides and subsequent fermentation of obtained sugars to valuable bioproducts. Current work compares chemistry and technological features of two different cooking processes in the preparation of polysaccharide substrates for deep sacchari-fication with P. verruculosum glycosyl hydrolases. Bleached kraft and sulfite pulps were subjected to hydrolysis with enzyme mixture of high xylanase, cellobiohydrolase and β-glucosidase activities at a dosage of 10 FPU/g of dry pulp and fiber concentration of 2.5, 5 and 10%. HPLC was used to analyze soluble sugars after hydrolysis and additional acid inversion of oligomers to monosaccharides. Kraft pulp demonstrated higher pulp conversion after 48 h (74-99%), mostly resulted from deep xylan hydrolysis. Sulfite-pulp hydrolysates, obtained in similar conditions, due to higher hexose concentration (more than 50 g/L), had higher fermentability for industrial strains producing alcohols, microbial protein or organic acids. Along with saccharification, enzymatic modification of non-hydrolysed residues occurred, which led to decreased degree of polymerization and composition changes in two industrial pulps. As a result, crystallinity of kraft pulp increased by 1.3%, which opens possibilities for obtaining new types of cellulosic products in pulp and paper industry. The high adaptability and controllability of enzymatic and fermentation processes creates prospects for the modernization of existing factories.

Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia associated with impaired carbohydrate, lipid and protein metabolism, with concomitant absence of insulin secretion or reduced sensitivity to its metabolic effects. Patients with diabetes mellitus have 30% more risk of developing heart failure and cardiovascular disease with respect to healthy people. Heart and cardiovascular problems are the first cause of death worldwide and the main complications which lead to high healthcare costs. Such complications can be delayed or avoided by taking prescribed medications in conjunction with a healthy lifestyle (i.e. diet and physical activity). The American College of Sports Medicine and the American Diabetes Association recommend that diabetic people reduce total sedentary time by incorporating physical activity in their weekly routine. This narrative literature review has the aim to summarize and present the main guidelines, pre-exercise cardiovascular screening recommendations, and considerations for patients with diabetes and comorbidities who are planning to participate in regular exercise regimens.

Mitochondria are involved in the regulation of cellular energy metabolism, calcium homeostasis, and apoptosis. For mitochondrial quality control, dynamic processes, such as mitochondrial fission and fusion, are necessary to maintain shape and function. Disturbances of mitochondrial dynamics lead to dysfunctional mitochondria which contribute to the development and progression of numerous diseases, including Type 2 Diabetes (T2D). Compelling evidence put forward that mitochondrial dynamics play a significant role in the metabolism-secretion coupling of pancreatic β cells. The disruption of mitochondrial dynamics is linked with defects in energy production and increased apoptosis, ultimately impairing insulin secretion and β cell death. This review provides an overview of altered mitochondrial dynamics in pancreatic β cells using ge-netic/pharmacologic approaches, and how these affect insulin secretion.

Canine mammary tumors (CMTs) are among the most common disease in female dogs and share similarities with human breast cancer, which have placed these animals as a model of study in comparative oncology. Metabolic reprogramming is one of them and is known as a hallmark of carcinogenesis whereby cells undergo adjustments to supply the high bioenergetic and biosynthetic demands of rapidly proliferating cells. However, such alterations are also vulnerabilities that may serve as therapeutic strategies which have been tested mostly in human clinical trials, but poorly explored in CMTs. In this dedicated review, we compilated the metabolic changes described for CMTs emphasizing the metabolism of carbohydrates, amino acids, lipids, and mitochondrial function. We observed here key factors associated with the presence and aggressiveness of CMTs, such as the increase in glucose uptake followed by enhanced anaerobic glycolysis via upregulation of glycolytic enzymes, changes in glutamine catabolism due to overexpression of glutaminases, raise in fatty acid oxidation and distinct effects depending on the lipid saturation, in addition to mitochondrial DNA which is a hotspot for mutations. Therefore, more attention should be paid to this topic given that targeting metabolic fragilities could improve the outcome of CMTs.

Alzheimer’s disease (AD) is characterized by the formation of senile plaques consisting fibrillated amyloid-β (Aβ), dystrophic neurites, and the neurofibrillary tangles of tau. The oligomers/fibrillar Aβ damages the neurons or initiate an intracellular signaling cascade for neuronal cell death leading to Aβ toxicity. The Aβ is a 4 kDa molecular weight peptide originating from the C-terminal region of the amyloid precursor protein via proteolytic cleavage. Apart from the typical AD hallmarks, certain deficits in metabolic alterations have been identified. This study describes the emerging features of AD from the aspect of alternation in the main pathway of carbohydrate metabolism in the human brain. Particularly, the neurons in patients with AD favor glycolysis despite a normal mitochondrial function indicating a Warburg-like effect. In addition, certain dietary patterns are well known for their properties in preventing AD. Among those, a ketogenic diet may substantially improve the symptoms of AD. An effective therapeutic method in the treatment, mitigation, and prevention of AD has not yet been established. Therefore, the researchers pursue the development and establishment of novel therapies effective in suppressing AD symptoms and the elucidation of their underlying protective mechanisms against neurodegeneration aiming for AD therapy in near future.

Nanocomposite hydrogels offer remarkable potential for applications in bone tissue engineering. They are synthesized through the chemical or physical crosslinking of polymers and nanomaterials, allowing for the enhancement of their behaviour by modifying the properties and compositions of the nanomaterials involved. However, their mechanical properties require further enhancement to meet the demands of bone tissue engineering. Here, we present an approach to improve the mechanical properties of nanocomposite hydrogels by incorporating polymer grafted silica nanoparticles into a double network inspired hydrogel (gSNP Gels). The gSNP Gels were synthesised via a graft polymerization process using a redox initiator. gSNP Gels were formed by grafting 2-acrylamido-2-methylpropanesulfonic acid (AMPS) as the first network gel followed by a sequential second network acrylamide (AAm) onto amine functionalized silica nanoparticles (ASNPs). We utilized glucose oxidase (GOx), to create an oxygen-free atmosphere during polymerization resulting in higher polymer conversion compared to argon degassing. The gSNP Gels showed excellent compressive strengths of 13.9 ± 5.5 MPa, a strain of 69.6 ± 6.4%, and a water content of 63.4% ± 1.8. The synthesis technique demonstrates a promising approach to enhance the mechanical properties of hydrogels, which can have significant implications for bone tissue engineering and other soft tissue applications.

Accumulation of extra fats in the body results in disturbance in homeostasis causing obesity. The pathophysiology of obesity has been associated with various genetic, epigenetic factors and the disturbed lifestyles of an individual. One of the outcomes is disturbance in the sleep cycle which leads to sleep disorders. The evolutionary significance of sleep lies in the fact that it saves energy and is crucial for adjustment of an individual to ecological and environmental factors, and thus maintains homeostasis. Sleep has an anabolic function and replenishes the wakefulness-associated loss of glycogen stores. However, the modern lifestyle is well known to disrupt sleep behavior and patterns affecting human health negatively. Alteration in homeostasis leads to several acute and chronic pathophysiological conditions like obesity and related metabolic morbidities being one amongst them. Shorter sleep duration and poor sleep quality are important risk factors associated with the development of obesity and have more adverse effects on energy homeostasis. Consequently, it is crucial to comprehend the obesity and sleep relationship and its therapeutic strategies, given that strong crosstalk exists between energy balance that favors obesity and sleep apnea. It is therefore highly recommended to the people with a high risk of obesity to maintain sleep discipline and good sleep hygiene in our daily life. Interventions are required to improve both sleep quality and quantity, and associated obesity. More focused research is needed for uncovering the pieces of evidence that determine whether such interventions can improve obesity-related health consequences. The present review discusses the important findings on the therapeutic and neuroendocrine mechanisms regulating sleep and obesity.

Keywords: Obesity; hypothalamus; appetite; glucose homeostasis; weight-loss drugs; AGRP; POMC; NTS; incretins.

Beyond plasma glucose-lowering in patients with type 2 diabetes, sodium- glucose cotransporter 2 inhibitors (SGLT2i) significantly reduced the hospitalization for heart failure (HF) and retarded the progression of chronic kidney disease (CKD). Endothelial dysfunction is not only involved in the development and progression of cardiovascular disease (CVD), and is also associated with the progression of CKD. In patients with type 2 diabetes, hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia induce the development of endothelial dysfunction. SGLT2i have shown an improvement in endothelial dysfunction, as assessed by flow-mediated vasodila-tion, in individuals at high risk for CVD. Along with an improvement of endothelial dysfunction, SGLT2i showed improvements in oxidative stress, inflammation, mitochondrial dysfunction, glucotoxicity such as advanced glycation end products signaling and nitric oxide bioavailability. The improvements in endothelial dysfunc-tion and such endothelium-derived factors may play an important role in preventing the development of coronary artery disease, coronary microvascular dysfunction and diabetic cardiomyopathy which cause HF and in retarding CKD. The suppression of the development of HF and the progression of CKD achieved by SGLT2i might have been largely induced by the improvement of vascular endothelial function by SGLT2i.

In humans and animal models, intermittent fasting (IF) interventions promote body weight loss, improve metabolic health, and are thought to lower cardiovascular disease risk. However, there is a paucity of reports on the relevancy of such nutritional interventions in the context of dyslipidemia and atherosclerotic cardiovascular diseases. The present study assessed the metabolic and atheroprotective effects of intermittent fasting intervention (IF) in atherosclerosis-prone apolipoprotein E-deficient (Apoe-/-) mice. Groups of male and female Apoe-/- mice were fed a regular (chow) or atherogenic (high-fat, high-cholesterol, HFCD) diet for 4 months, either ad libitum or in an alternate-day fasting manner. The results show that IF intervention improved glucose and lipid metabolism independently of sex. However, IF only decreased body weight gain in males fed chow diet and differentially modulated adipose tissue parameters and liver steatosis in a diet composition-dependent manner. Finally, IF prevented spontaneous aortic atherosclerotic lesions formation in mice fed chow diet, irrespective of sex but failed to reduce HFCD-diet-induced atherosclerosis. Overall, the current work indicates that IF interventions can efficiently improve glucose homeostasis and treat atherogenic dyslipidemia, but a degree of caution is warranted with regard to the individual sex and the composition of the dietary regimen.

Background: Nonalcoholic fatty liver disease (NAFLD) is regarded as a component of metabolic syndrome, which has insulin resistance (IR) as the primary physiopathological event. The aim of study was to establish the association between IR, assessed using triglyceride and glucose index (TyG), and histopathological features of NAFLD lesions. Methods: The study included patients with metabolic syndrome. Fasting plasma glucose (FPG), fasting lipid profiles and liver enzymes were measured. IR was assessed by TyG index. Liver biopsy was performed for assessment steatosis and fibrosis. Results: TyG index had a mean value of 8.93 ± 1.45, with a higher value in the patients with overweight (p=0.002) and obesity (p=0.004) than in the patients with normal weight. TyG index mean value of 8.78 ± 0.65 in subjects without NASH, 8.91 ± 0.57 in patients with borderline NASH and 9.13 ± 0.55 in patients with definite NASH. Significant difference was found between subjects without NASH and the ones with definite NASH (p=0.004). The analysis of the area under the ROC curve proved that TyG index is a predictor for NASH (p=0.043). Conclusion: TyG index is a facile tool used to identify individuals at risk for NAFLD, but not for the progression of liver lesions.

Sugar-sweetened beverages are associated with metabolic dysfunction, particularly in those with increased risk factors. Artificial sweeteners (AS) are often promoted as a healthier alternative, yet findings remain conflicting as to their effects on metabolic function. Further, there is a lack of data exploring the interaction between AS and high-fat diets (HFD). We therefore examined the effects of HFD and the AS Acesulfame-potassium (Ace-K) on glucose intolerance and adipose tissue physiology in male and female C57BL/6 mice. 40 mice were randomised to receive either a) a control diet (CDCon; standard control diet/water), b) control diet and Ace-k (CDAS; CD/7.5mM AS in drinking water), c) HFD (HFCon; HFD (45%kcal from fat)/water), or d) HF and AS (HFAS; HFD/7.5mM AS in drinking water) for 6 weeks. A HFD increased body weight in male and female mice independently of AS supplementation. AS induced sex-specific effects protecting against HFD-induced hyperglycaemia and adipocyte hypertrophy in male mice and reducing inflammatory gene expression in the adipose tissue. Conversely in females, AS induced hyperinsulinemia in HFD mice and increased expression of immune-related genes. These findings suggest that supplementation of HFD with AS exacerbates metabolic dysfunction in female mice. This work supports the importance of studying sexually dimorphic responses to an altered nutritional environment and highlights the need for further investigation into the intake of AS, particularly in those already at risk of metabolic disease such as the obese or overweight.

Non-enzymatic glucose sensing is a crucial field of study because of the current market demand. This study proposes a novel design of glucose sensor with enhanced selectivity and sensitivity by using graphene Schottky diodes, which is composed of Graphene/Platinum Oxide/n-Silicon heterostructure. The sensor was tested with different glucose concentrations and interfering solutions to investigate its sensitivity and selectivity. Different structures of the device were studied by adjusting the platinum oxide film thickness to investigate its catalytic activity. It was found that the film thickness plays a significant role in the efficiency of glucose oxidation and hence in overall device sensitivity. Moreover, theoretical investigations were conducted using Density Function Theory (DFT) to better understand the detection method and the origins of selectivity. The working principle of the sensors puts it in a competitive position with other non-enzymatic glucose sensors. DFT calculations provided a qualitative explanation of the charges distributed across the graphene sheet within a system of a platinum substrate with D-glucose molecules above. The proposed graphene/PtO/n-Si heterostructure has proven to satisfy these factors, which opens the door for further developments of more reliable non-enzymatic glucometers for continuous glucose monitoring systems.

Key features of glycogen metabolism in excitable tissues are not well-explained by current concepts. Glycogen stores in brain and skeletal muscle are generally considered to function as local glucose reserves, to be utilized during transient mismatches between glucose supply and demand; however, quantitative measures show that blood glucose supply is likely never rate-limiting for energy metabolism in either brain or muscle under physiological conditions. These tissues nevertheless do normally utilize glycogen during intervals of increased energy demand, despite the availability of free glucose, and despite the ATP cost of cycling glucose through glycogen polymer. This seemingly wasteful shunt can be explained by considering the effect of glycogenolysis on the amount of energy derived from ATP (ΔG’ATP). ΔG’ATP is diminished by elevations in Pi, such as occur at sites of rapid ATP hydrolysis and net phosphocreatine consumption. Glycogen utilization counters this effect by sequestering Pi in glycolytic metabolites (glycogen_n + Pi → glycogen_n-1 + glucose-1-phosphate → phosphorylated glycolytic intermediates), and thereby maintains the amount of energy obtained from ATP at sites of rapid ATP consumption. This thermodynamic effect may be particularly important in the narrow, spatially constricted astrocyte processes that ensheath neuronal synapses. This effect can also explain the co-localization of glycogen and cytosolic phosphocreatine in brain astrocytes, glycolytic super-compensation in brain when glycogen is not available, and aspects of exercise physiology in muscle glycogen phosphorylase deficiency (McArdle’s disease).

Introduction. The use of probiotics demonstrate efficacy against obesity and metabolic syndrome (MetS). Detection effective probiotic strains for hyperglycemia and immunity associated with is important task. The aim of the study was to evaluate an influence of Lactobacillus casei IMV B-7280 separately and composition L. casei IMV B-7280 / Bifidobacterium animalis VKB / B. animalis VKL on the levels of blood glucose and immunity in obese mice. Meterials and methods. Obesity was induced by fat-enriched diet (FED) in male BALB/c mice. Obese mice were transferred to standard diet and received per os probiotic strains daily during 10 days. We measured tumor necrosis factor-a (TNF-a) in blood serum using enzyme-linked immunosorbent assay and functional activity of peritoneal exudate macrophages (PEMs). Glucose levels in blood was defined with glucometer. Results. We ascertained that all probiotic strains induced reducing mice weight and visceral fat, normalization of TNF-a production and functional activity of PEMs. Treatment with L. casei IMV B-7280 was associated with decreasing blood glucose levels. No normalization of glucose and TNF-a levels in obese mice, transferred to standard diet without probiotic treatment, although we revealed decreasing their weight and visceral fat and partial recover of functional activity of PEMs. Conclusions. Probiotic strain L. casei IMV B-7280 (separately) and composition L. casei IMV B-7280 / B. animalis VKB / B. animalis VKL can re-equilibrate metabolic and inflammation indices in mouse obesity model. L. casei IMV B-7280 alone was more efficient in decreasing glucose levels than composition of strains.

The performance of modified electrode of nanocomposite film consisting of polypyrrole-chitosan-titanium dioxide (Ppy-CS-TiO2) has been explored as non-enzymatic glucose biosensors. The synergy effect of TiO2 nanoparticles and conducting polymer on the current response of electrode resulted in higher sensitivity for nanocomposite modified electrode. The incorporation of TiO2 nanoparticles in the nanocomposite films were confirmed by XPS spectra. The FESEM and HR-TEM provided more evidences for the presence of TiO2 in Ppy-CS structure. Glucose biosensing properties were determined by amperommetry and cyclic voltammetry (CV) methods. The interfacial properties of nanocomposite electrodes were studied by electrochemical impedance spectroscopy (EIS). The developed biosensors showed a good sensitivity over the liner range of 1-14 mM with a detection limit of 614 μM for glucose. It also exhibited good selectivity and long term stability with no interference effect. The Ppy-CS-TiO2 nanocomposites film presented high electron transfer kinetics.

Pituitary adenylate cyclase-activating polypeptide receptor 1 (PAC1-R) has a higher affinity for pituitary adenylate cyclase- activating polypeptide (PACAP) than for vasoactive intestinal peptide (VIP). PACAP exerts its neuroprotective effects through PAC1-R. PAC1-R has become a target for drug development, and we targeted PAC1-R to screen small positive allosteric modulator 1 (SPAM1). SPAM1 has a neuroprotective effects, and in the D-galactose (D-gal) mouse model, SPAM1 improved the structure of the hippocampal dentate gyrus and restored the number of neurons. Compared with D-gal model mice, SPAM1 treatment upregulated the expression of Sirtuin 6 (SIRT6) and Lamin B1, and downregulated the expression of YinYang 1 (YY1) and p16. Consistent with this, the same results were obtained in senescent RGC-5 cells. Meanwhile, SPAM1 was also found to up-regulate SIRT6 and down-regulate YY1 expression in normal RGC-5 cells. Then, we further explored the mechanism of SPAM1 neuroprotection by whole transcriptome sequencing and proteomic analysis, and found that SPAM is involved in the longevity regulating pathway, and confirmed the up-regulation of neurofilament light polypeptide and neurofilament medium polypeptide by western blot, thus laying a pharmacological foundation for SPAM1 as a therapeutic agent for neurodegenerative diseases. polypeptide and neurofilament medium polypeptide. Thus, it lays a pharmacological foundation for SPAM1 as a therapeutic drug for neurodegenerative diseases.

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.

Background. The type-2 sodium-glucose cotransporters inhibitors (SGLT2i) are a new relevant therapeutic option for patients affected by chronic heart failure with reduced ejection fraction (HFrEF). The aim of this study was to evaluate, in a real-world population from a single center, the feasibility of introducing SGLT2i and their interaction with other recommended drug classes. Methods. We evaluated the consecutive patients affected by chronic heart failure (CHF) since January 2022. At baseline clinical visit the therapy taken by the patients as well as that prescribed were accurately collected. During a 6-12 month follow-up the the changes in concomitant therapy were analyzed. Results. At baseline, among 350 patients evaluated, only 17 (5%) were already taking SGLT2i, 13 with HFrEF, 2 with CHF with mild reduced (HFmrEF) and 2 with preserved ejection fraction (HFpEF). After baseline evaluation, SGLT2i were prescribed to 220 (63%) of all the patients enrolled, among whom 178 (84%) of HFrEF patients, 25 (42%) of HFmrEF and 17 (22%) of HFpEF. After follow-up, SGLT2i therapy was highly tolerated and it was associated with a significant increased prescription of sacubitril/valsartan and a reduced use of diuretics. Finally, a significant improvement in functional status and left ventricular systolic function after SGLT2i therapy was observed. Conclusions. In this single center “real world” study, SGLT2i were prescribed in HFrEF patients most of all already in therapy with the other classes of drugs currently recommended for their treatment. Moreover, a further optimization in prescribed ther-apy was observed during a short term follow-up. These data further support the use of this thera-peutic approach in routine clinical practice.

Gossypol is a complex plant polyphenol reported to be cytotoxic and anti-inflammatory, but little was known about its effect on gene expression in macrophages. The objective was to explore gossypol’s toxicity and its effect on gene expression involved in inflammatory responses, glucose transport and insulin signaling pathway in mouse macrophages. Mouse RAW264.7 macrophages were treated with multiple concentrations of gossypol for 2-24 h. Gossypol toxicity was estimated by MTT assay and soluble protein content. qPCR analyzed the expression of anti-inflammatory tristetraprolin family (TTP/ZFP36), proinflammatory cytokine, glucose transporter (GLUT) and insulin signaling genes. Cell viability was greatly reduced by gossypol, accompanied with dra-matic reduction of soluble protein content in the cells. Gossypol treatment resulted in an increase of TTP mRNA level 6-20 fold and increased ZFP36L1, ZFP36L2 and ZFP36L3 mRNA levels by 26-69 fold. Gossypol increased proinflammatory cytokine TNF, COX2, GM-CSF, INFγ and IL12b mRNA levels up to 39-458 fold. Gossypol treatment upregulated mRNA levels of GLUT1, GLUT3 and GLUT4 genes as well as INSR, AKT1, PIK3R1 and LEPR but not APP genes. This study demonstrated that gossypol induced macrophage death and reduced soluble protein content that was accom-panied with massive stimulation of anti-inflammatory TTP family and proinflammatory cytokine gene expression as well as elevation of gene expression involved in glucose transport and insulin signaling pathway in mouse macrophages.

Olfactory Receptors (ORs) are a large family of G protein coupled receptors predominantly expressed by the main olfactory epithelium at nasal level and are responsible for the generation of smelling sense. Microarray and deep sequencing analyses, however, have demonstrated that ORs are ectopically expressed in various human tissues including testis, kidneys, adipose tissue and liver and their biological functions become to be unrevealed. Molecular and pharmacological approaches have shown that some of these ORs modulate glucose and lipid metabolism at multiple interfaces, suggesting that ORs might be part of the large family of nutrient sensors. i.e. molecular/ cellular machines that respond to a specific nutrient component. By using nutrients- derived agonists it has been shown that ORs effectively modulates glucose and lipid metabolism raising interest on their possible therapeutic application in the treatment of metabolic disorders including dyslipidemia, obesity and metabolic syndrome.

Currently, old-style personal medicare techniques rely mostly on traditional methods, such as cumbersome tools and complicated processes, which can be time-consuming and inconvenient in some circumstances. Furthermore, such old methods need the use of heavy equipment, blood draws, and traditional bench-top testing procedures. Invasive ways of acquiring test samples can potentially cause patients discomfort and anguish. Wearable sensors, on the other hand, may be attached to numerous body areas to capture diverse biochemical and physiological characteristics as a developing analytical tool. Physical, chemical, and biological data transferred via the skin is used to monitor health in various circumstances. Wearable sensors can assess the aberrant conditions of the physical or chemical components of the human body in real-time, exposing the body state in time, thanks to unintrusive sampling and high accuracy. Most commercially available wearable gadgets are mechanically hard components attached to bands and worn on the wrist, with form factors ultimately constrained by the size and weight of the batteries required for the power supply. Wearable gadgets with “skin-like” qualities are a new type of automation that is only starting to make its way out of research labs and into pre-commercial prototypes. In this paper, we studied the recent advancement in battery-powered wearable sensors established on optical phenomena and skin-like battery-free sensors which brings a breakthrough in wearable sensing automation.

A human organism depends on stable glucose blood levels in order to maintain the metabolic needs. Glucose is considered as the most important energy source and glycolysis is postulated as a backbone pathway. However, when glucose supply is limited, ketone bodies and amino acids can be used to produce enough ATP. In contrast, for the functioning of pentose phosphate pathway (PPP) glucose is essential and cannot be substituted by other metabolites. PPP generates and maintains levels of NADPH needed for reduction of oxidized glutathione and protein thiols, synthesis of lipids and DNA as well as for xenobiotic detoxification, regulatory redox signaling and counteracting infections. Flux of glucose into a PPP, particularly under extreme oxidative and toxic challenges is critical for survival, whereas the glycolytic pathway is primarily activated when glucose is abundant, and there is lack of NADP⁺ that is required for activation of glucose-6 phosphate dehydrogenase. An important role of glycogen stores in resistance to oxidative challenges is discussed. Current evidences explain disruptive metabolic effects and detrimental health consequences of chronic nutritional carbohydrate overload and provides new insights into positive metabolic effects of intermittent fasting, caloric restriction, exercise, and ketogenic diet through modulation of redox homeostasis.

Glucose-sensitive films were prepared by the layer-by-layer (LbL) deposition of poly(ethyleneimine) (H-PEI) solution and DNA solution (containing glucose oxidase (GOx)). H-PEI/DNA+GOx multilayer films were constructed using electrostatic interactions. The (H-PEI/DNA+GOx)5 film was then partially decomposed by hydrogen peroxide (H2O2). The mechanism for the decomposition of the LbL film was considered to involve a more reactive oxygen species (ROS) that was formed by the reaction of hemin and H2O2, which then caused nonspecific DNA cleavage. GOx present in the LbL films reacts with glucose to generate hydrogen peroxide. Therefore, decomposition of the H-PEI/DNA+GOx)5 film was observed when the thin film was immersed in a glucose solution. A (H-PEI/DNA+GOx)5 film exposed to a glucose solution for periods of 24, 48 72, and 96 h indicated decomposition of the film increased with the time. The rate of LbL film decomposition increased with the glucose concentration. At pH and ionic strength close to physiological conditions, it was possible to slowly decompose the LbL film at a sub-millimolar glucose concentration.

Graphene-based composites have been widely explored for electrode and electrocatalyst materials for electrochemical energy systems. In this paper, a novel composite material of the reduced graphene oxide nanosheets (rGON) with gold nanoparticles (NPs) (rGON-AuNP) is synthesized, and its morphology, structure and composition are characterized by SEM, HRTEM, XRD, EDX, FTIR, Raman, and UV-Vis techniques. To confirm this material’s electrochemical activity, a glucose oxidase (GOD) is chosen as the target reagent to modify the rGON-AuNP layer to form GOD/rGON-AuNP/glassy carbon (GC) electrode. Two pairs of distinguishable redox peaks, corresponding to the redox processes of two different conformational GOD on AuNP, are observed on the cyclic voltammograms of GOD/rGON-AuNP/GC electrode. Both cyclic voltammetry and electrochemical impedance spectroscopy are employed to study the mechanism of direct electron transfer from GOD to GC electrode on the rGON-AuNP layer. In addition, this GOD/rGON-AuNP/GC electrode shows catalytic activity toward glucose oxidation reaction.