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

Baijiu is popular with its long history and balanced flavor, and flavor type was the most widely used classification mode for Baijiu. However, the evolution relationship of Baijiu flavor types and the differential markers between flavor types are still unclear, which has greatly affected the development of Baijiu industry. In this study, a total of 319 trace components were identified by gas chromatography-olfactometry-mass spectrometry and gas chromatography-mass spectrometry. Among them, 91 trace components with high odor active values or taste active values were recognized as flavor components. Then random forests were conducted to screen differential markers between derived and basic flavor types, and principal component analysis was carried out to evaluate their effectiveness in distinguishing the flavor types of Baijiu. Finally, 19 differential markers were screened and proved to effectively reveal the evolution Baijiu flavor types, and were further verified as key differential markers by addition test and correlation analysis.

Glycated hemoglobin (HbA1c) is used to assess glycemic control in Type 1 diabetes (DM1) patients. Apolipoproteins play an essential role in DM1 pathophysiology and may be associated with complications, as well as HbA1c. This cross-sectional observational study consisting of 81 children and adolescents of both sexes diagnosed with DM1 investigated the relationship between body fat distribution and lean mass with HbA1C and apolipoprotein values analyzing biochemical and body composition measurements. Shapiro-Wilk test with Lilliefors correction, non-parametric Mann-Whitney test, and others were used with a significance level of 5%. The sample had a diagnosis time of 4.32 years and high blood glucose levels (mean 178.19 mg/dL) and HbA1c (mean 8.57%). Subjects also had a moderate level of adiposity, as indicated by arm and thigh fat areas. The study also found significant differences in the distribution of patients concerning levels of apolipoproteins A and B, with a smaller proportion of patients having undesirable levels. Finally, the study found a significant difference in the distribution of patients with estimated cardiovascular risk based on the ApoB/ApoA-1 ratio. Conclusively, visceral fat in children and adolescents with DM1 may increase the risk of DM1 long-term complications owing to its association with elevated HbA1C and apolipoprotein values.

This paper analyzed the main diseases of the friction high-strength bolt (FHSB) joints in order to study the characteristics of the corrosion products of the joints in steel bridge and the influence factors. Seven representative FHSB connection pairs and eight steel plate samples were selected from the Dongying Shengli Yellow River Bridge, which has been in operation for 33 years. Then Scanning Electron Microscope (SEM), Energy Dispersive Spectroscopy (EDS) and X-Ray Diffraction (XRD) were used to analyze the microscopic morphology and chemical composition of the corroded surface of the samples. Finally, this paper discussed the relationship between the corroded sample surface and the environmental corrosion. The research results showed that construction quality problems, such as non-standard hole expansion, segmental slab joint dislocation and contact surface pollution, accelerated corrosion of the contact surface. With the increase of corrosion degree of joints, the contact surface of aluminum spraying layer gradually changed from a rugged and dense state to a smooth and porous powder state. With the corrosion of the steel plate substrate, the contact surface gradually changed from a fluffy stratified state to a surface bonding state. It was inferred that the friction coefficient of the FHSB connection node on the corroded aluminum sprayed contact surface first decreased and then increased. The corroded node samples detected not only a large number of S and Cl elements, but also the oxides of Mn, Si and other elements as well as FeS. It was speculated that node corrosion was also related to atmospheric (acid rain) and industrial dust and other corrosive environments. Almost all samples detected the component SiO2 of the Yellow River soil, as well as Mg, Ca, K, Na and other elements at the same time, which is basically consistent with the component elements of the Yellow River soil. Therefore, it was inferred that it was related to the inclusion of the Yellow River soil.

Background and Aim: Cancer is a disease characterized by uncontrolled cell growth and invasion of tissues. It seems that personality differences and psychological factors are important factors that lead to different reactions to cancer. Therefore, the main purpose of the present study was to investigate the relationship between type D, stress level of life events, personality traits, and anxiety sensitivity in people with breast cancer attending to Tehran Bu-ali Hospital. Methods: The study was a correlational study in which 100 cancer patients referred to Bu-ali Hospital in Tehran, selected by the available sampling method from April to June 2018. The tools used included the Denollet DS-14 Type D Questionnaire, the Paykel Life events Questionnaire, the Eysenck Personality Questionnaire, the ASI Anxiety Scale, Floyd et al., Data analysis in this study is taken place by using SPSS software, two descriptive levels (percentage, frequency, etc.) and regression. Results: The study results showed that there is a relationship between type D personality with stress of life events, neurosis, extraversion, and psychopath dimensions of personality and anxiety sensitivity in breast cancer patients. Conclusion: Psychological factors play a role in the incidence and exacerbation of breast cancer, and ultimately patients with personality type D and personality traits such as psychosis and high anxiety sensitivity and more stress of life events show more symptoms.

Systemic lupus erythematosus (SLE) is a heterogenous autoimmune disease. While its etiology remains elusive, current understanding suggests a multifactorial process with contributions by genetic, immunologic, hormonal, and environmental factors. A hypothesis that combines several of these factors proposes that genomic elements, the L1 retrotransposons, are instrumental in SLE pathogenesis. L1 retroelements are transcriptionally activated in SLE and produce two proteins, ORF1p and ORF2p, which are immunogenic and can drive type I interferon (IFN) production by producing DNA species that activate cytosolic DNA sensors. In addition, these two proteins reside in RNA-rich macromolecular assemblies that also contain well-known SLE autoantigens like Ro60. We surmise that cells expressing L1 will exhibit all the hallmarks of cells infected by a virus, resulting in a cellular and humoral immune response similar to those in chronic viral infections. However, unlike exogenous viruses, L1 retroelements cannot be eliminated from the host genome. Hence, dysregulated L1 will cause a chronic, but perhaps episodic, challenge for the immune system. The clinical and immunological features of SLE can be largely explained by this model. Here we review the support for, and the gaps in, this hypothesis of SLE and its potential for new diagnostic, prognostic, and therapeutic options in SLE.

The purpose of this narrative review is to provide an overview of the latest literature on bariatric and metabolic surgery for diabetes mellitus type II and obesity (diabesity) and to discuss its implications for future research and clinical practice.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that acts on the pancreas to increase insulin and decrease glucagon secretion. Albuminuria is the pivotal marker for diabetic nephropathy, which is the leading microvascular complication of diabetes mellitus. Most of the previous studies mainly focused on the clinical trials of the therapeutic renal protective effect after administration of GLP-1 receptor agonists (GLP-1 RAs), not prior to administration. Therefore, this study aimed to investigate the association between fasting plasma GLP-1 levels and albuminuria before GLP-1 RA administration. A cross-sectional study was designed to evaluate the association between fasting plasma GLP-1 levels and albuminuria in patients with type 2 diabetes mellitus (T2DM). A total of 68 T2DM participants were analyzed from the data at Wonkwang University Hospital in Iksan, Korea. Logistic regression analysis was performed to evaluate the odds ratio (OR) and 95% confidence interval (CI) of the incidence of albuminuria between the GLP-1 low group (Group L) and the high group (Group H). The OR (95% CI) for the incidence of albuminuria comparing the Group L with the Group H of fasting plasma GLP-1 levels was 3.410 (1.160-10.023), p = 0.026 after adjustment for age, gender, fasting plasma glucose, HbA1c, C-peptide, the use of ACE inhibitors or ARBs, SGLT-2 inhibitors, and DPP-4 inhibitors. As a continuous variable, the OR (95% CI) for the incidence of albuminuria associated with the reduction of each 1 pmol/L in fasting plasma GLP-1 levels was 1.673 (1.173-1.870), p = 0.018, after full adjustment. This study showed the negative association between fasting plasma GLP-1 levels and the incidence of albuminuria in Korean patients with T2DM, before GLP-1 RA administration. This result suggests that endogenous GLP-1 may play a role in attenuating albuminuria.

Type 2 diabetes (T2D) has a complex pathophysiology which makes modeling the disease difficult. We aimed to develop a novel model for simulating T2D in vitro, including hyperglycemia, hyperlipidemia, and variably elevated insulin levels targeting muscle cells. We investigated insulin resistance (IR), cellular respiration, mitochondrial morphometry and the associated function in different T2D -mimicking conditions in rodent skeletal (C2C12) and cardiac (H9C2) myotubes. Physiological controls included 5mM glucose with 20mM mannitol as osmotic controls. To mimic hyperglycemia, cells were exposed to 25mM glucose. Further treatments included insulin, palmitate, or both. After short-term (24h) or long-term (96h) exposure, we performed radioactive glucose uptake and mitochondrial function assays. Mitochondrial size and relative frequencies were assessed by morphometric analyses using electron micrographs. C2C12 and H9C2 cells treated short- or long-term with insulin and/or palmitate and HG showed IR. C2C12 myotubes exposed to T2D -mimicking conditions showed significantly decreased ATP-linked respiration and spare respiratory capacity, and less cytoplasmic area occupied by mitochondria, implying mitochondrial dysfunction. In contrast, H9C2 myotubes showed elevated ATP-linked and maximal respiration and increased cytoplasmic area occupied by mitochondria, indicating better adaptation to stress and compensatory lipid oxidation in a T2D environment. Both cell lines displayed elevated fractions of swollen/vacuolated mitochondria after T2D -mimicking treatments.Our stable and reproducible in vitro model of T2D rapidly induced IR, changes in ATP-linked respiration, shifts in energetic phenotypes, and mitochondrial morphology, which are comparable to the muscles of patients suffering from T2D. Thus, our model should allow studying disease mechanisms, potential new targets, and screen candidate therapeutic compounds.

Oral vaccines are highly envisaged for veterinary applications due to their convenience and ability to induce protective mucosal immunity as the first line of defense. The present investigation harnessed live-attenuated Salmonella Typhimurium to orally deliver novel expression vector systems containing the Cap and Rep genes from porcine circovirus type 2 (PCV2), a significant swine pathogen. The antigen expression by the vaccine candidates JOL2885 and JOL2886, comprising eukaryotic pJHL204 and pro-eukaryotic expression pJHL270 plasmids respectively, was confirmed by western blot and IFA. We evaluated their immunogenicity and protective efficacy through oral vaccination in a mouse model. This approach elicited both mucosal and systemic immunity against PCV2d. Oral administration of the candidates induced PCV2-specific sIgA, serum IgG antibodies, and neutralizing antibodies, resulting in reduced viral loads in the livers and lungs of PCV2d-challenged mice. T-lymphocyte proliferation and flow-cytometry assays confirmed enhanced cellular immune responses after oral inoculation. The synchronized elicitation of both Th1 and Th2 responses was also confirmed by enhanced expression of TNF-α, IFN-γ, IL-4, MHC-I, and MHC-II. Our findings highlight the effectiveness and safety of the constructs with an engineered-attenuated S. Typhimurium, suggesting its potential application as an oral PCV2 vaccine candidate.

High hepcidin is linked to low-grade inflammation and lower iron levels. The consequence of testosterone replacement therapy (TRT) on inflammation and risk of cardiovascular disease (CVD) is undetermined. We investigate the effect of TRT on the inflammatory cardiovascular risk markers hepcidin-iron, fibroblast growth factor 23 (FGF23)-phosphate-klotho, and calprotectin pathways. Methods: A randomized, placebo-controlled, double-blinded study at an academic tertiary-care medical center. Interventions were testosterone gel (TRT, n=20) or placebo gel (n=19) for 24 weeks. We included 39 men (50─70 years) with type 2 diabetes (T2D) on metformin monotherapy with bioavailable testosterone levels <7.3 nmol/L. Body composition was assessed by DXA- and MRI-scans; main study outcomes were serum hepcidin-iron, FGF23, phosphate, klotho, and calprotectin. Results: Hepcidin levels decreased during TRT (β=-9.5 ng/mL, P<0.001), lean body mass (β=1.9 kg, P=0.001) increased, and total fat mass (β=-1.3 kg, P=0.009) decreased compared to placebo. Delta hepcidin was not associated with changes in lean body mass or fat mass. Iron and the pathways of FGF23-phosphate-klotho and calprotectin were unchanged during TRT. Conclusions: During TRT, the reduction in hepcidin was not associated with circulating iron levels, lean body mass, or fat mass; these findings suggested a direct anti-inflammatory effect of TRT and no indirect effect mediated through these factors.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by elevated blood glucose levels. Despite the availability of pharmacological treatments, dietary plans, and exercise regimens, T2DM remains a significant global cause of mortality. Consequently, there is a growing interest in exploring lifestyle interventions, such as Intermittent Fasting (IF). This study aims to identify underlying patterns and principles for effectively improving T2DM risk parameters through IF. By analyzing data from multiple randomized clinical trials investigating various IF interventions in humans, a machine learning algorithm was employed to develop a personalized recommendation system. This system advises pre-diabetic and diabetic individuals on the most suitable IF interventions to improve T2DM risk parameters. With a success rate of 95%, this recommendation system offers highly tailored guidance, optimizing intermittent fasting's benefits for diverse population subgroups. The results of this study allow us to conclude that weight is the crucial feature for females, while age is the determining factor for males to reduce glucose levels in blood. By revealing patterns in diabetes risk parameters among individuals, this study not only provides practical guidance but also sheds light on the underlying mechanisms of T2DM, contributing to a deeper understanding of this complex metabolic disorder.

The creation of crop-type maps from satellite data has proven challenging, often impeded by a lack of accurate in-situ data. This paper aims to demonstrate a method for crop-type (ie. Maize, Wheat and Other) recognition based on Convolutional Neural Networks using a bottom-up approach. We trained the model with a highly accurate dataset of crowdsourced labelled street-level imagery. Classification results achieved an AUC of 0.87 for wheat, 0.85 for maize and 0.73 for other. Given that wheat and maize are the two most common food crops globally, combined with an ever-increasing amount of available street-level imagery, this approach could help address the need for improved crop-type monitoring globally. Challenges remain in addressing the noisy aspect of street-level imagery (ie. buildings, hedgerows, automobiles, etc.), where a variety of different objects tend to restrict the view and confound the algorithms

The odontogenic cysts can lead to a bone destruction that can hamper the dental implant place-ment in the ideal 3D position. Different biomaterials and techniques that allow bone regeneration are described in the literature, each with its advantages and disadvantages. This clinical case with 18 months of follow-up shows the enucleation of an odontogenic cyst fol-lowing the guide bone regeneration with fence technique. After 6 months 2, dental implants were placed at the region of tooth 11 and 21, being rehabilitated nine weeks after. The fence technique allowed the recovery of the bone morphology and the placement of the dental implants in the 3D ideal position.

The rising global population amidst the growing concerns of climate change will have a dire consequence on global food security and socio-economic activities. Wheat is one of the most important staple foods consumed by more than four billion people in the world, but climate change impacts account for a decline of 5.5% in wheat yield and predictions indicate that the production could further dwindle by nearly 30% in 2050, due to trends in temperature, precipitation, and carbon dioxide. An effective annual crop estimate is necessary not only to inform government the status of national food security, but also is used to determine the benchmark on which agricultural commodities are priced in the market. Thus, annual crop monitoring and yield estimate is paramount to determine the amount of wheat imports required to make up for the shortfalls in the national wheat production in South Africa, which has been a net importer of wheat since 1998. A joint project between South Africa and Poland investigated satellite based-crop growth monitoring using Sentinel 2 and determined the most distinguishable crop phenology for an accurate winter wheat classification during the growing season from August – December with Random Forest (RF) algorithm. The winter wheat crop was more accurately identified during the crop ‘heading’ stage in October yielding the highest user’s (75.56%) and producer’s (92.52%) accuracies, despite the relatively lower overall accuracy (78.14%) compared to that of December with OA of 83.58% obtained during the maturity stage. This study, therefore, confirms the suitability of sentinel 2 for an effective phenology-based winter wheat crop classification during the heading stage, reducing the ambiguity of spectral confusion created with surrounding grass and maize crops.

This paper presents a novel DQ-based multicarrier Pulse Width Modulation PWM for a single-phase, three-level PV-powered grid-connected F-type inverter. The main control objective in the proposed inverter is to regulate the grid current with low total harmonic distortion and load power components compensation. Despite the F-type inverter’s advanced advantages, there are only a few works addressing the control issue in the literature yet. The proposed control and switching methods aim to achieve both DC side voltage balance and lowest switching losses. The proposed scheme has been designed based on a modified multi-carrier PWM switching algorithm. Consequently, the proposed control method able to satisfy the requirements of DC side voltage balance and achieve lower switching losses. A further advantage of the proposed control and switching methods is that they retain the main advantage of the F-Type inverter, which is that only 25% of the power switches are exposed to full DC voltage. This is an important advantage since it reduces the overall cost of the inverter and improves its reliability. Overall, the proposed modified multi-carrier PWM switching algorithm appears to be a promising approach for controlling the F-Type inverter, offering improved performance and efficiency compared to other control methods. The theoretical model was verified through simulation using MATLAB/Simulink. According to the simulation results, the grid current and dc capacitor voltages are successfully managed in all operational situations.

Since the discovery of mitochondrial-derived peptides (MDP), their participation in cellular metabolism is no longer considered as the sole function of the mitochondria, but importance was also attached to its role as a source of protective factors of metabolic stress. These peptides are encoded in the mitochondrial genome and translated into the mitochondria or cytoplasm, to signal within the cell or be released and bind to membrane receptors. The objective of this work was explored and compare the frequency of MT-RNR1 and MT-RNR2 variants in sequences obtained from T2D individuals and control population. 213 different mitochondrial polymorphisms previously reported in the literature associated with T2D and cardiovascular diseases were analyzed. We can found three variants in the MT-RNR1 not related with MOTS-c coding sequence: m.1189T>C (rs28358571), m.1420T>C (rs111033356), and m.1438A>G (rs2001030); and secondly, three polymorphisms associated to MT-RNR2 m.2667T>C (rs878870626) related to humanin, m.1811A>G (rs28358576) in SHPL3 and m.3027T>C (rs199838004) in SHPL6 associated with statistical differences between the T2D and control group. All these findings were previously related to cardiovascular complications in literature and, as far as we know, relating for the first time in diabetic patients.

Abstract Objectives: The purpose of this study was to determine whether breast cancer and diabetes status are related in adult Americans. Methods: We conducted a cross-sectional study of 7,599 individuals from the National Health and Nutrition Examination Survey (NHANES). Diabetes was classified as type 2 diabetes and pre-diabetes. Both prediabetes and diabetes were diagnosed according to ADA 2014 guidelines. Multiple logistic regression analysis was used to explore the relationship between diabetes status and breast cancer. Results: We found that prediabetes (OR = 0. 60, 95% CI:(0. 40, 0. 88), P= 0. 009613) and non-diabetes (OR = 0.05.3,95% CI: (0.34, 0.83), P = 0. 006014) were associated with a reduced risk of breast cancer in comparison to Type 2 diabetes (literature). Prediabetes in non-Hispanic blacks was associated with a reduced risk of breast cancer (OR=0. 55,95%CI:0. 40-0. 75, P<0. 001). Using two segmented linear regression models to fit the relationship between BMI and breast cancer, we found that the relationship between BMI and breast cancer was nonlinear, but there was a threshold effect. The threshold effect analysis found that BMI affcted breast cancer at an inflection point 26. 3 Kg/m2. Adjusted OR (95% CI) on both sides of the turning point was 1. 0799 ( 1. 0029, 1. 1629 ) and 0. 9873 ( 0. 9638, 1. 0115 ), respectively. Conclusions: Diabetes status is associated with the risk of breast cancer development. Moreover, the risk of developing breast cancer steadily increased from nondiabetes to prediabetes and type 2 diabetes. In addition, the prevalence of breast cancer showed a gradual increase withincreasing BMI up to 26. 3 Kg/m2 with the highest prevalence of breast cancer. There was an inverse U-shaped relationship between BMI and the breast cancer prevalence.

Objective: Type I interferon receptor (IFNAR) signaling contributes to several autoimmune and vascular diseases such as atherosclerosis and stroke. The purpose of this study was to assess the influence of IFNAR1 deficiency on the formation and progression of experimental abdominal aortic aneurysms (AAAs). Methods: AAAs were induced in type I interferon receptor subunit 1 (IFNAR1) deficient and wild type control male mice via intra-infrarenal aortic infusion of porcine pancreatic elastase. Immunostaining for IFNAR1 was evaluated in experimental and clinical aneurysms. The initiation and progression of experimental AAAs was assessed via ultrasound imaging prior to (day 0) and 3-, 7-, and 14-days following elastase infusion. Aneurysmal histopathology was analyzed at sacrifice. Results: Increased aortic medial and adventitial IFNAR1 expression was present in both clinical AAAs harvested at surgery and experimental AAAs. Following AAA initiation, wild type mice experienced progressive, time-dependent infrarenal aortic enlargement. This progression was substantially attenuated in IFNAR1 deficient mice. On histological analyses, medial elastin degradation, smooth muscle cell depletion, leukocyte accumulation and neoangiogenesis were markedly diminished in IFNAR1 deficient as compared to wild type mice. Conclusion: IFNAR1 deficiency limited experimental AAA progression in response to intra-aortic elastase infusion. Combined with clinical observations, these results suggest a regulatory role for IFNAR1 activity in AAA pathogenesis.

The wind industry is looking for ways to accurately predict the reliability and availability of newly installed wind turbines. Failure modes, effects and criticality analysis (FMECA) is a technique utilized for determining the critical subsystems of wind turbines. There are several studies which applied FMECA for wind turbines in the literature, but no studies so far have considered different weather conditions or climatic regions. Furthermore, various design types of wind turbines have been analyzed applying FMECA but no study so far has applied FMECA to compare the reliability of geared and direct-drive wind turbines. We propose to fill these gaps by using Koppen-Geiger climatic regions and two different turbine models of direct-drive and geared-drive concepts. A case study is applied on German wind farms utilizing the WMEP database which contains wind turbine failure data from 1989 to 2008. This proposed methodology increases the accuracy of reliability and availability predictions and compares different wind turbine design types and eliminates underestimation of impacts of different weather conditions.

Lifestyle is the primary prevention of diabetes, especially type-2 diabetes (T2D). Nutritional intake of olive oil (OO), the key Mediterranean diet component has been associated with the prevention and management of many chronic diseases including T2D. Several OO bioactive compounds such as monounsaturated fatty acids, and key polyphenols including hydroxytyrosol and oleuropein, have been associated with preventing inflammation and cytokine-induced oxidative damage, glucose lowering, reducing carbohydrate absorption and increasing insulin sensitivity and related gene expression. However, research into the interaction of OO nutraceuticals with lifestyle components, especially physical activity is lacking. Promising postprandial effects have been reported when OO or other similar monounsaturated fatty acids was the main dietary fat compared with other diets. Animal studies have shown a potential anabolic effect of oleuropein. Such effects could be further potentiated via exercise, especially strength training, which is an essential exercise prescription for individuals with T2D. There is also an evidence from in vitro, animal and limited human studies for a dual preventative role of OO polyphenols in diabetes and cancer, especially that they share similar risk factors. Putative anti-oxidative and anti-inflammatory mechanisms and associated gene expressions resulting from OO phenolics, have produced paradoxical results making suggested inferences from dual prevention T2D and cancer outcomes difficult. Well-designed human interventions and clinical trials are needed to decipher such a potential dual anti-cancer and anti-diabetic effects of OO nutraceuticals. Exercise combined with OO consumption, individually or as part of a healthy diet is likely to induce reciprocal action for T2D prevention outcomes.

Rapid urbanization, increasing population and increased industrialization to cater to demands of the growing population has imposed upon us a huge environmental cost. The significantly deteriorated air quality across the globe is associated with a direct and indirect impact on public health. While associated disorders such as chronic obstructive pulmonary diseases, heart failures are well documented, less is known about the biological basis of the process. We hypothesize that the worsening air quality may likely impact common systemic inflammatory processes, thus driving communicable and non-communicable diseases alike.Receptor mediated entry of particulate matter (PM2.5) results in activation of signaling cascades which culminate in production of inflammatory chemokine and cytokine responses, traversing through the blood mediating impacting not only on other organs but also dysbiosis of microflora. For the purpose of the review we choose tuberculosis (TB) as a model for communicable infectious disease and type 2 diabetes mellitus (T2DM) as a marker for non-communicable disorder. The increasing prevalence of these co-morbidities and the burdening of public health systems justifies this example. However the hypothesis may be applicable to other inflammation driven disorders also.

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

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

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

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

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

Despite effective vaccines, yellow fever outbreaks persist, increasing the urgency to find antivirals for patient treatment. This study aimed to discover compounds with potential antiviral properties against the wild-type yellow fever virus (wt-YFV) in Hippeastrum puniceum, of the Amaryllidaceae family, through bioassay-guided fractionation of the crude bulb extract using ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution ESI-QTOF mass spectrometry and subsequent analysis of the pharmacokinetic and toxicological properties (ADMET) of the annotated compounds. In the active fractions against wt-YFV, six alkaloids were proposed such as bulbisine, cathinone, trigonelline, tetrahydroharman-3-carboxylic acid, and 2,7-dimethoxyhomolycorine (or 3-O-acetylnarcissidine). Co-occurring in these fractions were the amino acids arginine, asparagine, tryptophan, and glutamic acid. In silico ADMET analysis of the alkaloids predicted good absorption, distribution, excretion, favorable metabolization profiles, and non-mutagenic toxicity, indicating their potential for drug development. These findings justify further in vitro assessment of the compounds against YFV and in vivo testing in animal models. This strategy seems to be an efficient approach for discovering antiviral compounds against YFV. Such discoveries hold promise not only in combating YFV but also in addressing a spectrum of other flaviviruses.

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

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

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

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

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

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

Background: Comorbidities have been frequently reported in COVID-19 patients, which often lead to more severe outcomes. The underlying molecular mechanisms behind these clinical observations have not yet been explained. Herein, we investigated the disease-specific gene expression signatures that may induce susceptibility to SARS-CoV-2 infection. Methods: We studied 30 frequently occurring acute, chronic, or infectious diseases of recent times that have shown comorbidity in one or another respiratory disease(s) caused by pathogenic human infecting coronaviruses, especially SARS-CoV-2. We retrieved array-based gene expression data for each disease and control from relevant datasets. Subsequently, all the datasets were quantile normalized, and log-2 transformed data was used for analysis. Results The expression of ACE2 receptor and host proteases, namely FURIN and TMPRSS2 that are essential for cellular entry of SARS-CoV-2, was upregulated in all six studied subtypes of leukemia (hereafter, referred as leukemia). The expression of ACE2 was also increased in psoriasis, lung cancer, Non-alcoholic fatty liver disease (NAFLD), breast cancer, and pulmonary arterial hypertension patients. The expression of FURIN was higher in psoriasis, NAFLD, lung cancer, and in type II diabetic liver, whereas it was lowered in breast cancer. Similarly, the expression of TMPRSS2 was increased during lung cancer and type II diabetes; it was decreased during psoriasis, NAFLD, lung cancer, breast cancer, and cervical cancer.Furthermore, a heightened expression of genes that are involved in immune response was observed in leukemia patients, as shown by the higher expression of IFNA2, IFNA8, IFNA10, IFNA14, IFNA16, IFNA21, IFNB1, CXCL10, and IL6. The expression of JAK1, STAT1, IL6, and CXCL10 was higher in NAFLD. Besides, JAK1 and STAT1 were upregulated in type II diabetic muscles. In addition, most of the upregulated genes in COVID-19 patients showed a similar trend in leukemia, NAFLD, and psoriasis. Furthermore, SARS-CoV-2, SARS-CoV and MERS CoV, were found to commonly alter two genes, namely, CARBONIC ANHYDRASE 11 and CLUSTERIN.Conclusions: The genes that may confer susceptibility to SARS-CoV-2 infection are mostly upregulated in leukemia patients; hence, leukemia patients are relatively more susceptible to develop COVID-19, followed by other chronic disorders, such as, NAFLD, type II diabetes, psoriasis, and hypertension. This study identifies key genes that are altered in the studied diseases types, which may aid in the infection of SARS-CoV-2 and underlie COVID-19 associated comorbidities.

This study describes, through a retrospective analysis, the epidemiological and clinicopathological findings of gas gangrene in horses in the Amazon biome. The study includes observations made in 20 animals from 2018 to 2023 by reviewing the clinical records of horses with muscle and mobility injuries treated at proprieties in the Amazon biome. The affected horses exhibited a sudden onset of severe lameness, swelling, and crepitus in the affected limb. The rapid progression of symptoms, including intense pain, fever, and toxemia, led to the clinical suspicion of gas gangrene. Immediate treatment was crucial, involving aggressive surgical debridement to remove necrotic tissue and high doses of broad-spectrum antibiotics to combat the infection. Despite these efforts, the condition of the horses deteriorated rapidly due to the aggressive nature of the disease and the challenging environment of the Amazon, which complicates timely veterinary intervention. The age range of the affected horses was from four months to 12 years, with a greater frequency in those over 12 months (80%, 16/20). Necropsy revealed histopathological lesions characterized by intense muscle necrosis, liquefaction, and gas formation, suggestive of Clostridium infection. The diagnosis was confirmed by multiplex PCR.

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

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

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

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

Background: Cardiovascular comparisons between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and Sodium-glucose co-transporter-2 (SGLT-2) inhibitors in type 2 diabetes(T2D) remain an area of interest. Thus, the purpose of this meta-analysis is to compare the impact of these two drug classes on major CV outcomes, such as heart failure hospitalization(HHF), major adverse cardiovascular events (MACE), CV mortality, myocardial infarction, stroke, and all-cause mortality, with an emphasis on heart failure hospitalizations. Methods: PubMed (including MEDLINE), Google Scholar, Cochrane Central Library, PLOSONE, and Science Direct databases were searched for studies that compared GLP-1 RAs and SGLT-2 inhibitors in patients with type 2 diabetes. Six cohort studies were selected for the analysis. Odds ratios (OR) with 95% CI were calculated and a random-effects model was used to estimate the hazard ratios (HR) of the studies. The quality of the studies was evaluated using the Newcastle-Ottawa Scale (NOS), and publication bias was assessed using funnel plots and Egger’s test. Results: Pooled analysis demonstrated a significant reduction in heart failure hospitalizations with SGLT-2 inhibitors compared to GLP-1 RAs (HR: 0.78 [0.62–0.98], I² = 87%, p < 0.01). Cardiovascular mortality was also significantly reduced by SGLT-2 inhibitors (HR: 0.74 [0.31–1.67], I² = 87%, p < 0.01), and a modest reduction was observed for all-cause mortality (HR: 0.85 [0.44–1.64], I² = 17%, p = 0.27). While SGLT-2 inhibitors appeared to slightly reduce the risk of myocardial infarction (HR: 0.83 [0.74–0.92], I² = 0%, p = 0.85), no significant difference was observed for MACE (HR: 0.91 [0.82–1.01], I² = 0%, p = 0.70) or stroke (HR: 0.88 [0.77–1.00], I² = 0%, p = 0.85). Conclusions: Compared to GLP-1 receptor agonists, SGLT-2 inhibitors were more effective in lowering heart failure hospitalizations and cardiovascular mortality in patients with type 2 diabetes. It was also found that all-cause mortality and myocardial infarction were moderately reduced using oral agents. However, the differences were not significant for MACE or stroke. These results imply that SGLT-2 inhibitors may potentially provide better cardiovascular benefits, especially with respect to heart failure and cardiovascular mortality, than GLP-1 RA. Further research should be conducted to determine the effects of the long-term use of these therapies on stroke and other cardiovascular events.

In the present paper, the (p,q)-Hermite based Apostol type Frobenius-Euler polynomials and numbers are firstly considered and then diverse basic identities and properties for the mentioned polynomials and numbers, including addition theorems, difference equations, integral representations, derivative properties, recurrence relations. Moreover, we provide summation formulas and relations associated with the Stirling numbers of the second kind.

Introduction: ophthalmological assessment of the retinal circulation and the level of VEGF-A is currently considered a non-invasive and safe diagnostic tool to assess the peripheral microcircu-lation Objective: to study retinal hemodynamics and VEGF-A levels in patients with type 1 diabetes mellitus after pancreas transplantation Settings and Design: A prospective, single-stage, single-center, non-randomized clinical trial Methods: 79 patients (158 eyes) with type 1 diabetes mellitus and end-stage diabetic nephropathy participated in the study. Patients were divided into 3 groups: group 1, potential recipients of pancreas and kidney transplant from the waiting list; group 2, patients after kidney transplanta-tion; and group 3, patients after simultaneous pancreas and kidney transplantation. Ophthalmo-logical examination included measuring the macular hemoperfusion density. The level of VEGF-A was examined in the patients' tear by enzyme immunoassay. Results: retinal hemoperfusion density and VEGF-A concentration were expected to correlate with the severity of diabetic changes in the fundus of patients. A lower index of retinal hemoperfusion density and a high level of VEGF-A were noted in patients with proliferative ret-inopathy and macular oedema. Group 3 showed the lowest frequency of the active phase of the proliferative retinopathy and retinal macular oedema, characterized by a higher retinal hemoperfusion density in the foveal and the parafoveal zone of the macular region, and low VEGF-A concentration in tear. Conclusion: measurement of retinal hemoperfusion density and determination of tear VEGF-A concentration are informative objective methods for diagnosing the severity of diabetic changes of the fundus.

Testicular granulosa cell tumors (TGCTs) are rare tumors of sex cord stromal origin. TGCTs can be classified into the adult type and the juvenile type. The adult type is extremely rare with only 93 known cases reported in the literature. We, herein, present a report of a case of a 30 year old male patient who presented with a testicular mass, underwent radical inguinal orchiectomy and the pathology examination revealed an adult type granulosa tumor. We additionally review the literature to summarize the scientific knowledge of an entity barely described worldwide.

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

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

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

The endoplasmic reticulum (ER) plays a multifunctional role in lipid biosynthesis, calcium storage, protein folding, and processing. Thus, maintaining ER homeostasis in insulin-secreting beta-cells is essential. Several pathophysiological conditions and pharmacological agents disrupt the ER homeostasis, thereby causing ER stress. The cells react to ER stress by initiating an adaptive signaling process called the unfolded protein response (UPR). However, the ER initiates death signaling pathways whenever the ER stress persists. ER stress has been linked to several diseases, such as cancers, obesity, and diabetes. Thus, the regulation of ER stress may provide possible therapeutic targets for many diseases. Current evidence suggests that chronic hyperglycemia and hyperlipidemia linked to type II diabetes disrupt ER homeostasis, resulting in irreversible UPR activation and cells death. Despite much progress in understanding the pathophysiology of UPR and ER stress, to date, the mechanisms of ER stress in relation to type II diabetes remain unclear. This review provided up-to-date information regarding the current status of UPR, ER stress mechanisms, insulin dysfunction, oxidative stress, and the therapeutic potential of targeting specific ER stress pathways.

Motivated by Kim-Kim [19] introduced the new type of degenerate poly- Bernoulli polynomials by means of the degenerate polylogarithm function. In this paper, we define the degenerate poly-Frobenius-Euler polynomials, called the new type of degenerate poly-Frobenius-Euler polynomials, by means of the degenerate polylogarithm function. Then, we derive explicit expressions and some identities of those numbers and polynomials.

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

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

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

This paper evaluates the feasibility of applying Massive MIMO to tackle the uplink mixed-service communication problem. Under the assumption of an available physical narrowband shared channel (PNSCH), devised to exclusively consume data traffic from Machine Type Communications (MTC) devices, the capacity (i:e:, number of connected devices) of MTC networks and, in turn, that of the whole system, can be increased by clustering such devices and letting each cluster share the same time-frequency physical resource blocks. Following this research line, we study the possibility of employing sub-optimal linear detectors to the problem and present a simple and practical channel estimator that works without previous knowledge of the large-scale channel coefficients. Our simulation results suggest that the proposed channel estimator performs asymptotically as well as the MMSE estimator with respect to the number of antennas and the uplink transmission power. Furthermore, the results also indicate that, as the number of antennas is made progressively larger, the performance of sub-optimal linear detection methods approaches the perfect interference-cancellation bound. The findings presented in this paper shed light on and motivate for new and exciting research lines towards a better understanding of the use of massive MIMO in MTC networks.

In this paper we introduce the hypo-q-operator norm and hypo-q-numerical radius on a Cartesian product of algebras of bounded linear operators on Banach spaces. A representation of these norms in terms of semi-inner products, the equivalence with the q-norms on a Cartesian product and some reverse inequalities obtained via the scalar reverses of Cauchy-Buniakowski-Schwarz inequality are also given.

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

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

Nitrogen and phosphorous support the ecosystem by supplying nutrients to algae and aquatic plants. Having them in excess results in the eutrophication of waters creating quality problems. In the past, nitrogen has been widely investigated for wells in the context of groundwater flow. However, a national-scale nitrogen assessment in rivers and streams has not received enough attention. In this research, the Wilcoxon rank sum test, as a non-parametric hypothesis testing method, has been applied to nitrogen concentration in the form of nitrate-nitrogen and nitrite-nitrogen in rivers and streams of the Contiguous United States. This approach was particularly selected because of the non-normal and positively skewed nitrogen levels occurring in the surface flow. This method was able to identify the impaired body of waters as well as quantify the confidence, significance, and errors involved. The Northern Appalachians (NAP), Northern Plains (NPL), and Xeric (XER) ecoregions were worsening in the nitrogen-nitrate condition with NAP, and XER needed immediate actions. The nitrite-nitrogen condition did not pose an immediate threat, so mitigation plans should focus more on nitrate-nitrogen remediation. It was shown that the method was superior to the two-sample t-test by yielding lower type II errors.

DKA represents an acute, severe complication of relative insulin deficiency and a common presentation of Type 1 Diabetes Mellitus (T1DM) primarily and, occasionally, T2DM in children and adolescents. It is characterized by the biochemical triad of hyperglycaemia, ketonaemia and/or ketonuria, and acidaemia. Clinical symptoms include dehydration, tachypnoea, gastrointestinal symptoms, and reduced level of consciousness, precipitated by a variably long period of polyuria, polydipsia and weight loss. The present review aims to summarize potential pitfalls in the diagnosis and management of DKA. A literature review was conducted using the Pubmed/Medline databases including articles published from 2000 onwards. Diagnostic challenges include differentiating between T1DM and T2DM, DKA and hyperosmolar hyperglycaemic state (HHS), or between DKA and alternative diagnoses presenting with overlapping symptoms, such as pneumonia, asthma exacerbation, urinary tract infection, gastroenteritis, acute abdomen and central nervous system infection. The mainstays of DKA management include careful fluid resuscitation, timely intravenous insulin administration and restoration of shifting electrolyte disorders and underlying precipitating factors. However, evidence suggests that optimal treatment remains a therapeutic challenge. Accurate and rapid diagnosis, prompt intervention and meticulous monitoring are of major importance to break the vicious cycle of life-threatening events and prevent severe complications during this potentially fatal medical emergency.

Misuse of measurement units and orientations leads to errors in scientific applications, Cyber Physical Systems (CPS), and IoT C/C++ programs. Standard type system are inadequate in preventing such errors. Although dimensional and orientational analysis in physics can manually detect these errors in equations, analyzing complex code with intricate physical computations is impractical. To overcome this challenge, we propose an advanced type system that incorporates units and orientations as integral components within a specialized type library. Our enhanced type system automatically detects potential errors during compile time by representing physical quantities as types and utilizing dimensional analysis, orientational analysis, and metaprogramming techniques. Our improved type system enables formal verification of C++ software, successfully verifying programs with extensive codebases. We also employ it for runtime verification of dynamic linking and pointer operations in C++ programs. The integration of compile-time verification, dimensional analysis, orientational analysis, and advanced type system enhances the robustness and accuracy of scientific applications, CPS, and IoT C/C++ programs. By leveraging these approaches, we ensure precise calculations and prevent errors related to measurement units and orientations, resulting in substantial improvements in reliability and accuracy.

Dyslipidemia is a disorder where abnormally lipid concentrations circulate in the bloodstream. The disorder is common in type 2 diabetics (T2D) and is linked with T2D comorbidities, particularly cardiovascular disease. Dyslipidemia in T2D is typically characterized by elevated plasma triglyceride and low high-density lipoprotein cholesterol (HDL-C) levels. There is a significant gap in the literature regarding dyslipidemia in rural parts of Africa, where lipid profiles may not be routinely captured through standard surveillance activities. This study aimed to characterize the prevalence and demographic profile of dyslipidemia in T2D patients in the rural community of Ganadougou, Mali. We performed a cross-sectional study of 104 subjects with T2D in Ganadougou between November 2021 and March 2022. Demographic and lipid profiles were collected through cross-sectional surveys and blood tests. The overall prevalence of dyslipidemia in T2D patients was 87.5% (91/104), which did not differ by sex (p = .368). High low-density lipoprotein cholesterol (LDL-C) was the most common lipid abnormality (78.9%, [82/104]). Dyslipidemia was associated with age and hypertension status (p = .013 and p = .036, respectively). High total and high LDL-C parameters were significantly associated with hypertension (p = .029 and p = .006, respectively). In low-resource settings such as rural Mali, there is a critical need to improve infrastructure for routine dyslipidemia screening to guide its prevention and intervention approaches. The high rates of dyslipidemia observed in Gandadougou, consistent with concomitant increases in cardiovascular diseases in Africa suggest that lipid profile assessments should be incorporated into routine medical care for T2D patients in African rural settings.

Background: Dynapenia and non-alcoholic fatty liver disease (NAFLD) are common, especially in the middle and advanced-age diabetic male population. We aimed to examine the clinical features, NAFLD severity, and parameters associated with the presence of dynapenia in type 2 diabetes mellitus (T2DM) cases. Material and Methods: One hundred thirty-five male patients diagnosed with T2DM between 45 and 65 years of age were included. Patients were staged by ultrasonography according to NAFLD status. Results: There were significant differences in muscle strength, upper arm circumference, calf circumference, and up-and-go test scores between the NAFLD groups (p<0.001 for all). The frequency of dynapenia was lower, and arm and calf circumferences were higher in patients without NAFLD. The muscle strength, upper arm circumference, calf circumference, and up-and-go test scores were significantly lower in the dynapenic group compared to the non-dynapenic group (p<0.005 for all). The prevalence of dynapenia increased along with the increase in NAFLD stages (p<0.001). Conclusions: We detected a significant association between NAFLD and dynapenia in middle-aged men with T2DM. As muscle strength decreases, the amount of fat in the liver increases, and as the fat in the liver increases, muscle strength decreases.

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.

Type 2 diabetes has been linked to the expression of Human Leukocyte Antigens, principally to the major Histocompatibility Complex Class II and only scarce reports to Major Histocompatibility Complex class I in specific populations. The objective of the present work was to explore the presence of polymorphisms in the MHC class I related to Type 2 diabetes in the Mexican population using the GWAS SIGMA database. This database contains information of 3,848 Mexican individuals with type 2 diabetes and 4,366 control individuals from the same population without clinical or hereditary history of the disease. The searching criteria considered a P value < 0.005 and odds ratio, OR > 1.0. Ten novel statistically significant nucleotide variants were identified: four polymorphisms associated with HLA-A (A*03:01:01:01), and six with HLA-C (C*01:02:01:01). These alleles have a high prevalence in Latin American populations and could potentially be associated with autoimmunity mechanisms related with the development of Type 2 diabetes complications.

Type 2 diabetes (T2D) is characterized by hyperglycemia and insulin resistance. Cocoa may slow T2D development and progression. This study employed male and female BTBR.Cg-Lepob/ob/WiscJ and wild type (WT) controls to assess the potential for cocoa to ameliorate progressive T2D and compare responses between sexes. Mice received diet without (WT, ob/ob) or with cocoa extract (ob/ob + c) for 10 weeks. Glucose and insulin tolerance tests (GTT/ITT) were conducted at weeks 1, 5 and 2, 6, respectively. Cocoa provided mild non-significant protection against weight gain vs. ob/ob control in males but not females. Male ob/ob + c had increasing fasting glucose at weeks 1 and 5 GTTs, with significantly higher levels of fasting glucose than ob/ob control at week 5. This was not seen in females. Cocoa protected against elevated 4-hour fasting glucose in week 2, but not week 6, ITTs. Cocoa partly suppressed hyperinsulinemia in males but significantly amplified it in females and protected against loss of beta cell area in females only. The mechanisms of these sex-specific effects remain to be elucidated. This study informs additional experiments with larger sample sizes and demonstrates that sex differences must be considered when designing dietary interventions for T2D.

Acid fracturing simulation is used widely to optimize carbonate reservoirs and improve acid fracturing treatment performance. In this study, a method was used to minimize the risk of the acid fracturing treatment. First, optimal fracture geometry parameters with UFD methods are calculated. After that, design components change as long as fracture geometry parameters reach their optimal values. The results showed a high flow rate needed to achieve optimal fracture geometry parameters with increasing acid volume. Sensitivity analysis was performed on controllable and reservoir parameters. It observed that a high flow rate should be applied for a low fluid viscosity to achieve the optimization goals. Straight acid reaches optimal conditions at a high flow rate and low volume. These conditions for retarded acids appear only at a low flow rate and high volume. The study of the acid concentration for gelled acid showed that as it increased, the flow rate and volume increased. Besides, for low permeability formation, a large fracture half-length and small fracture width are desirable. In this case, a higher flow rate will be required. The sensitivity analysis showed that the optimum flow rate and acid volume increase and decrease for the high Young's modulus. The effect of closure stress was also investigated and observed for a sample with high closure stress, low flow rate, and high acid volume are required.

The Corona Virus Disease 2019 (COVID-19) outbreak is becoming pandemic with the highest mortality in people with associated comorbidities. These RNA viruses containing four structural proteins usually use spike protein to enter the host cell. It has been demonstrated that Angiotensin Converting Enzyme 2 (ACE2) ,as a part of renin-angiotensin-aldosterone system (RAAS), acts as a host receptor for the virus which is the main target of therapeutic approaches. However, medications acting on RAAS can lead to serious complications especially in people with diabetes and hypertension. To avoid this, other potential treatment modalities should be used in COVID-19 patients with associated comorbidities.

Aim: To perform a descriptive analysis of eating patterns and biophysical conditions of previously diagnosed and currently under treatment individuals from a semi-urban Mayan community of Yucatan, and to contrast them with T2DM therapeutic guidelines. Methods: The present study is derived from a randomized clinical trial conducted at Komchen, Yucatan. Participants’ diagnosed with T2DM were included. A 24-hour dietary recall, anthropometric parameters (weight, visceral fat, height, and waist circumference), biochemical (HbA1c) and clinical (blood pressure) variables were evaluated and compared via hypothesis test with T2DM treatment cut-off points (based on World Health Organization criteria). Results: Anthropometric characteristics differ significantly from the ideal criteria. Obesity prevalence within women with T2DM was 92.9%. Only 21% of the participants were under T2DM control (≤7%). Energy and carbohydrates consumption, significantly exceed therapeutic guidelines, whereas protein, fat, and fiber intake were lower than the recommendations. Conclusions: Komchen’s diet, concomitantly with food characteristics, could be related to glycemic decontrol. There is a disproportion in macronutrients consumption in favor of carbohydrates, probably associated with socioeconomic limitations, food availability, and price. Developing nutritional assistance programs which contemplate cultural and economic factors in this Mayan population must be taken into consideration.

Bianchi type III string cosmological models (massive and geometric) in presence of magnetic field with vacuum energy density following the techniques used by Letelier (1979) and Stachel (1980) are obtained. We find that the energy conditions (dominant as well as weak) given by Hawking and Ellis (1974) are satisfied for the models. Also the solutions obtained satisfy conservation equation for massive string with magnetic field and vacuum energy density. The models in general, represent anisotropic phase of space-time due to the presence of string. However, the models isotropize at late time and in special case. It has also been shown that the magnetic field is directly linked with the matter. For string dust model, the state finder parameters {r,s} are in excellent agreement with Planck results (Sahni et al. (2003)). The physical and geometrical aspects of the models with special cases are also discussed.

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

Introduction: When analyzing the current situation in Spain, derived from our current lifestyles far from following a Mediterranean lifestyle, there is an alarming prevalence of diabesity, which increases the global risk of suffering from cardiovascular disease (CVD) and decreases the quality of life related to health (QLRH). In order to guarantee, beyond glycemic control of patients with type 2 diabetes (DM2), adequate control of cardiovascular risk factors (CVRF) in DM2, it will be necessary to carry out a community intervention focused on the application of education programs focused on promoting the acquisition of healthy eating habits through the Mediterranean diet (DMED). This dietary pattern, together with physical exercise, has been shown to contribute to improving the QLRH of patients. Objective: To analyze the quality of life related to health, present in patients with poorly controlled type 2 diabetes, to determine the possible relationship between this and the degree of adherence to the Mediterranean diet and to examine whether there are differences between the sexes. Material and methods: Observational descriptive study in 93 patients diagnosed with DM2 with poor glycemic control (1Ac ≥ 7%), carried out in various health centers in Albacete and Cuenca, in which the baseline relationship between adherence to DMed and the HRQoL. They were administered a data collection sheet that included a survey of the degree of adherence to the DMed (MEDAS-14) and QLRH (SF-12v2) in the Primary Care (PC) medical and nursing consultations. The variables were analyzed: age groups, sex, years of evolution of DM2, body mass index (BMI), as well as basal glycemia (GB) and glycosylated hemoglobin (HbA1c). The “MEDAS-14” (adherence to DMED) was the main variable and the “SF-12v2” (QLRH) was the secondary variable. Material and methods: Observational descriptive study in 93 patients diagnosed with DM2 with poor glycemic control (1Ac ≥ 7%), carried out in various health centers in Albacete and Cuenca, in which the baseline relationship between adherence to DMed and the HRQoL. They were administered a data collection sheet that included a survey of the degree of adherence to the DMed (MEDAS-14) and QLRH (SF-12v2) in the Primary Care (PC) medical and nursing consultations. The variables were analyzed: age groups, sex, years of evolution of DM2, body mass index (BMI), as well as basal glycemia (GB) and glycosylated hemoglobin (HbA1c). The “MEDAS-14” (adherence to DMED) was the main variable and the “SF-12v2” (QLRH) was the secondary variable. Results: Patients with poorly controlled DM2 and with low adherence to the MedDM show a non-significantly greater affectation in the physical sphere: fair general state of health, physical function I (limitation to make moderate efforts such as moving a table, vacuuming or walk more than an hour), physical function II (limitation to climb several flights of stairs), physical role (problems at work or daily activities doing less than loved ones), physical role II (they had to stop performing some tasks at work or activities of daily living) and regular body pain. Presenting less affectation in the mental field: emotional role I, emotional role II, mental health I, vitality and mental health II. Without affectation in the social function since they consider that rarely the emotional or physical problems have hindered their social activities. Conclusions: Diabetic patients with poor glycemic control have low adherence to the MedMD (<9 points) and have poor QLRH. Low adherence to the DMed and obesity are related to a greater affectation in the physical dimension and less affectation in the mental dimension without affectation in the "social function".

The interference-fit size has a significant effect on CFRP/Al-alloy laminates riveted lap joints, the requirements for the interference-fit size are different because of the strengthening of heterogeneous materials. However, in the process of the riveted CFRP/Al-alloy, the heterogeneous laminates lead to poor structural strength because of the different requirements of interference-fit size. Therefore, the different assembly types of riveting mold are designed to acquire a novel interference-fit size, and the tensile test is adopted to evaluate the tensile property. In addition, the fracture failure of CFRP/Al-alloy laminates riveted lap joint is observed by the ultra-depth of field microscope. Finally, the best assembly type is the trapezoid riveting mold combined with an arc riveting die, and the sidewall intersection angle of the trapezoid riveting mold is 66° which could achieve a suitable interference-fit size and a better mechanical performance.

Diabetes is a group of diseases characterized by loss of β cell mass and/or -function, resulting in hyperglycemia. Approx. 537 million people worldwide suffer from diabetes – a number which is expected to increase. Diabetes is primarily treated by exogenous insulin, which comes with the challenges of maintaining glycemic control to prevent ketoacidosis and severe complications. The need for a curative treatment has initiated the research in β cell regeneration. Several studies in mice have identified essential genes for β cell fate, which can be manipulated in other cells to induce generation of new β cells. Zebrafish, a regeneration-positive animal model, has shown several different sources of new β cells, including regeneration by self-replication, neogenesis by duct-associated progenitor cells, and transdifferentiation of other endocrine islet cells. The animal models used in this research area are either limited by their low regenerative ability (mice), or their small size and remoteness from humans (zebrafish). There is a need for new animal models of diabetes, in which the molecular pathways of endogenous regeneration can be studied. This study proposes the axolotl salamander (Ambystoma mexicanum) as a model for studying the regeneration of β cells. The axolotl has shown great regenerative capability, as they have proven capable of regenerating amputated limbs, and hearts with myocardial infarction, among other organs. This study aims to establish a diabetic axolotl model, investigate their regenerative ability in the pancreas, and examine the potential systemic effects of the induced disease. In a pilot study, five different protocols using STZ (streptozotocin) were tested, and the most optimal protocol was found. Furthermore, the glucose tolerance test was optimized to characterize the glycemic state of the animals. The effect of the treatment on blood glucose levels was measured to characterize the development and decline of the disease. The histological changes in the pancreas were examined. Moreover, the systemic effects of the STZ treatment were investigated in blood and urine. The study indicated that it is possible to induce diabetes in the axolotl, but variations between the animals should be minimized, or the sample size should be increased to conduct a satisfying experiment, as it was not possible to induce diabetes in all animals. Regeneration was not observed histologically, but a restoration of blood glucose levels was seen over the span of the experiment. Lastly, edema formation was observed in some of the STZ-treated animals, but the cause of edema remains undetermined.

Bacterial nitroreductase enzymes that convert prodrugs to cytotoxins are valuable tools for creating transgenic targeted ablation models to study cellular function and cell-specific regeneration paradigms. We recently engineered a nitroreductase (“NTR 2.0”) for substantially enhanced reduction of the prodrug metronidazole, which permits faster cell ablation kinetics, cleaner interrogations of cell function, ablation of previously recalcitrant cell types, and extended ablation paradigms useful for modelling chronic diseases. To provide insight into the enhanced enzymatic mechanism of NTR 2.0, we have solved the X-ray crystal structure at 1.85 Angstroms resolution and compared it to the parental enzyme, NfsB from Vibrio vulnificus. We additionally present a survey of reductive activity with eight alternative nitroaromatic substrates, to provide access to alternative ablation prodrugs, and explore applications such as remediation of dinitrotoluene pollutants. The predicted binding modes of four key substrates were investigated using molecular modelling.

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.

Type 1 Diabetes mellitus (T1DM) occurs when insulin is not produced in the Pancreas due to the autoimmune destruction of the beta cells. The patients may be diagnosed after 80-90% of the beta cells are destroyed. Insulin remains the essential medicine in T1DM management, under continuous monitoring of glucose levels. T1DM management consists of a complex and precise set of self-care measures for the entire life; during this continuous process, the patients could become overwhelmed, angry, anxious, frustrated, and/or discouraged. Therefore, to be widely used and provide general benefits, new technologies for DM management must provide clinical advantages without compromising safety. The compliance of T1DM patients is also essential, thus improving their quality of life (QoL). Moreover, the accessibility of the new system for patients through healthcare coverage is critical; they must be able to buy the new devices and accessories and pay for their maintenance. In this context, our work aims to describe the most recent technologies regarding continuous glucose monitors (CGMs) and continuous subcutaneous insulin infusion (CSII) systems, correlated with psychosocial impact and capacity to improve T1DM patients' life quality.

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.

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

In this study we summarized our work on various aspects of colorectal adenocarcinomas, 1 focusing on tumor distribution (left- sided, right- sided, and rectal cancers), histologycal type, patient 2 age, gender and several factors affecting prognosis. These predictive and prognostic factors include 3 peritumoral budding, lymphovascular ant perineural invasion, lymph node metastasis, mismatch 4 repair status, and corellations with some frequently known mutations in colorectal adenocarcinomas, 5 detected using Next- Generation Sequencing (NGS) platform. This comprehensive approach allowed 6 us to explore how these factors interplay and influence the clinical outcome of patients with colorectal 7 adenocarcinoma. Additionaly, our findings contribute to the understanding of how genetic mutations 8 may correlate with histological features and prognostic markers, potentially guiding personalized 9 treatment strategies in the future. In our study, we do not claim to have exhausted the research on 10 the topic, and we fully recognized the need for more extensive and in-depth studies in this area of 11 tumor pathology.

There are no theorems (proven theories) in the biological sciences. We propose that the 3 31 nt minihelix tRNA evolution theorem be universally accepted as one. The 3 31 nt minihelix theorem completely describes evolution of type I and type II tRNAs from ordered precursors (RNA repeats and inverted repeats). Despite diversification of tRNAome sequences, statistical tests overwhelmingly support the theorem. Furthermore, the theorem relates the dominant pathway for the origin of life on Earth, specifically, how tRNAomes and the genetic code may have coevolved. Alternate models for tRNA evolution (i.e., 2 minihelix, convergent and accretion models) are falsified. In the context of the pre-life world, tRNA was a molecule that via mutation could modify anticodon sequences and teach itself to code. We relate the clearest history to date of the chemical evolution of life on Earth. From analysis of tRNA evolution, ribozyme-mediated RNA ligation was a primary driving force in evolution of complexity during the pre-life to life transition on Earth.

This study presents structural analysis and optimization for the lightweight design of a buoyant rotor-type permanent magnet (BRPM) generator, which was first presented in Bang (2010), and compares its structural performances to a conventional generator with a spoke arm-type rotor and stator. The main benefit of a BRPM is that it can be realized as a bearing-less drive system, free from the mechanical failure of rotor bearings, by using a buoyant rotor. Also, the deformation of a generator by blade vibration can be effectively suppressed using joint couplings between the blades and the rotor. For the design optimization, the objective is set as the mass of the rotor and the stator, and the maximum deformation of the airgap clearance between the rotor and the stator by external forces is constrained below 10% of the gap width. The commercial software Optistruct is used for the analysis and optimization. In this investigation, the analysis and optimization are conducted for a 10 MW wind turbine generator. However, the proposed methods can be extended to larger generator designs without requiring considerable modification. The mass of the opti-mized 10MW BRPM generator is 160.7 tons (19.3 tons for the rotor and 141.4 tons for the stator) while that of an optimized conventional spoke arm-type generator is obtained as 325.6 tons.

Type 2 diabetes mellitus may be complicated with chronic complications including diabetic neuropathy (DN). Timely diagnosis is crucial in treatment and maybe reversal of this complication. C reactive protein to albumin ratio (CAR) is considered as a marker of inflammation in various diseases that characterized with acute or chronic inflammation. Since diabetic neuropathy and type 2 diabetes mellitus are also associated with chronic, low grade inflammation, we aimed to study CAR levels of type 2 diabetic subjects with diabetic neuropathy and to compare to those in patients without diabetic neuropathy. Type 2 diabetic patients presented to our institutional outpatient clinics were divided into two according to the presence of DN. Subjects with DN were listed as DN group and others were as non-DN group. Characteristics and laboratory data, including CAR, in DN and non-DN groups were compared. Median CAR of the DN and non-DN groups were 2,19 (0,2-49)% and 0,56 (0,02-5,8)%, respectively (p&lt;0.001). CAR was significantly and positively correlated with age (r=0.15, p&lt;0.001), weight (r=0.19, p=0.01), BMI (r=0.11, p=0.03), waist circumference (r=0.10, p=0.046), fasting plasma glucose (r=0.14, p=0.004), serum creatinine (r=0.25, p&lt;0.001), triglyceride (r=0.17, p&lt;0.001), and LDL-cholesterol (r=0.13, p=0.001) levels. Moreover, CAR was inversely correlated with eGFR levels (r=-0.16, p&lt;0.001). The sensitivity and specificity of CAR (when higher than 1,02%) in predicting diabetic neuropathy were 78% and 73%, respectively (AUC: 0.84, p&lt;0.001, 95% CI: 0,82-0,87). Moreover, high CAR level was an independent risk factor of diabetic neuropathy (p&lt;0.001, OR: 1.34, 95% CI: 0.48-1.62). In conclusion, elevated CAR levels could be considered as a marker of diabetic neuropathy.

p-type Ag-N dual acceptor doped ZnO thin films with long electrical stability were deposited by DC magnetron reactive co-sputtering technique. After deposition, the films were annealed at 400 °C for one hour in a nitrogen-controlled atmosphere. The deposited films were amorphous. However, after annealing they crystallize in the typical hexagonal wurtzite structure of ZnO. The Ag-N dual acceptors were incorporated substitutionally in the structure of zinc oxide and achieving that the three samples presented the p-type conductivity in the ZnO. Initial electrical properties showed a low resistivity of from 1 to10^{−3} Ω.cm, Hall mobility of tens cm2/V.s and a hole concentration from 10^{17} to 10^{19} cm^{−3}. The electrical stability analysis reveals that the p-type conductivity of the ZnO:Ag,N films is very stable and does not revert to n-type, even after 36 months of aging. These results reveal the feasibility of using these films for applications in short-wavelength or transparent optoelectronic devices.

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.

Not only does this paper present a novel type-2 fuzzy system for identification and behavior prognostication of an experimental solar cell set and a wind turbine, but also it brings forward an exquisite technique to acquire an optimal number of membership functions and the corresponding rules. It proposes a seven-layered NCPRT2FS. For fuzzification in the first two layers, Gaussian type-2 fuzzy membership functions with uncertainty in the mean, are exploited. The third layer comprises rule definition and the forth one embeds fulfillment of type reduction. The three last remained layers are the ones in which resultant left–right firing points, two end-points and output all get assessed correspondingly. It should not be neglected off the nutshell that recurrent feedback at the fifth layer exerts delayed outputs ameliorating efficiency of the suggested NCPRT2FS. Later in the paper, a modern structural learning, established on type-2 fuzzy clustering, is held forth. An adaptively rated learning back-propagation algorithm is extended to adjust the parameters ensuring the convergence as well. Eventually, solar cell photo-voltaic and wind turbine are deemed as case studies. The experimental data are exploited and the consequent yields emerge so persuasive.

Manganosalen complexes are coordination compounds that possess a chelating salen-type ligand, a class of bis-Schiff bases obtained by condensation of salicylaldehyde and a diamine. They may act as catalytic antioxidants mimicking both the structure and the reactivity of the native antioxidant enzymes active site. Thus, manganosalen complexes have shown to exhibit superoxide dismutase, catalase, and glutathione peroxidase activities, and they could potentially facilitate the scavenging of excess ROS, thereby restoring the redox balance in the damaged cells and organs. Initial catalytic studies compared the potency of these compounds as antioxidants in terms of rate constants of the chemical reactivity against ROS, giving catalytic values approaching and even exceeding that of the native antioxidative enzymes. Although most of these catalytic studies lack of biological relevance, subsequent in vitro studies have confirmed the efficiency of many manganosalen complexes in oxidative stress models. These synthetic catalytic scavengers, cheaper than natural antioxidants, have accordingly attracted intensive attention for the therapy of ROS-mediated injuries. The aim of this review is to focus on in vivo studies performed on manganosalen complexes and their activity on the treatment of several pathological disorders associated with oxidative damage. This disorders, ranging from the prevention of fetal malformations to the extension of lifespan, include neurodegenerative, inflammatory and cardiovascular diseases, tissue injury, and other damages related to liver, kidney or lungs.

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

Human endogenous retroviruses (HERV) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV promoting pathological conditions including the development of autoimmunity, neurodegenerative disease and cancer. What infections then trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases Crohn’s, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis and autoimmune thyroiditis. MAP is also associated with Parkinson’s disease. Autoimmune diabetes, multiple sclerosis and rheumatoid arthritis are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via unsilencing of HERV. We examine the link between the ever-increasing number of MAP- associated diseases, the MAP/HERV intersection with these diverse medical conditions and propose treatment opportunities based upon this association.

This paper proposes an analytical model of the double-stator spoke-type permanent-magnet vernier machine (DSSTVM) using the subdomain model (SDM), which can be used to calculate the mag-netic field distribution and corresponding electromagnetic parameters of the DSSTVM. The whole field domain is divided into several subdomains according to the magnetic characteristics of each region, within which Laplace's and Poisson's equations are solved accordingly in terms of magnetic vector potential (MVP). Then, the magnetic flux density distribution, back electromotive force (EMF), and electromagnetic torque of the DSSTVM can be obtained correspondingly. Ultimately, finite element analysis (FEA) is adopted to validate the proposed analytical model's effectiveness for quickly predicting the no-load and on-load performances of the DSSTVM.

Rising child obesity rate creates a need for tools quantifying metabolic changes in obese children and adolescents for purposes of comorbidities early detection or prevention. A candidate for such role seem to be miRNAs – in vivo serving as the suppressing factors of the gene expression. The aim of this study was to review the recent discoveries in this field and to conclude directions of research or application of studied molecules. Repeated browsing of databases, followed by screening for eligibility of results, led to final approval of 9 articles. Filtered studies examined the differences in miRNA (miR) expression levels of obese subjects and children suffering from obesity comorbidities. Studies concerning the endothelial dysfunction (ED) identified miR-630 as a possible treatment option. Search for the alternative markers in diagnosis of non-alcoholic fatty liver disease (NAFLD) suggested value of miR-199a-5p and miR-122. MiR-486, miR-146b and miR-15b may serve as a panel of markers grading the development of type 2 diabetes mellitus (T2DM) in children, although further research raised doubts in that matter. Another panel of miRNA molecules was indicated as useful in early detection of alterations leading to metabolic syndrome (MetS). No valid link between studied miRNAs and atherosclerosis (AS) was found. MiRNAs seem to be promising prognostic markers for the diagnosis of NAFLD, T2DM and MetS in children. Further studies are required to support these findings.

The study aimed to estimate the prevalence and association between sarcopenia and blood biochemical parameters, nutritional intake, anthropometric measurements, physical performance, and physical activity in patients with Type 2 Diabetes Mellitus (T2DM). According to the diagnosis criteria of the Asian Working Group for Sarcopenia (AWGS) in 2019, 110 patients with T2DM (aged: 50–80 years) were divided into three groups: Non-sarcopenia (n = 38), Possible Sarcopenia (n = 31, 28.2%), and Sarcopenia (n = 41, 37.3%). Blood samples were collected and nutritional intake was evaluated by a registered dietitian. A food frequency questionnaire and Godin leisure-time exercise questionnaire were used to assess their daily vitamin D intake and physical activity. There were significant differences in age, serum vitamin D3 levels, nutritional intake, anthropometric measurements, and physical performance between the three groups. In elderly patients with T2DM, there was a significant association between sarcopenia with BMI, body fat percentage (BF%), and dietary energy and protein intake. Low serum vitamin D3 is a significant risk factor for possible sarcopenia.

Crimean-Congo hemorrhagic fever virus (CCHFV) is the causative agent of a tick-borne infection with significant mortality rate of up to 40% in the endemic areas, with evidence for geographical expansion. Lacking effective therapeutics and control measures, the development of protective CCHFV vaccine remains a crucial public health task. This manuscript describes, for the first time, a Bovine herpesvirus type 4 (BoHV-4) based viral vector (BoHV4-∆TK-CCHFV-N) and its immunogenicity and protection potential in BALB/c and IFNAR^-/- mice models in comparison with Adenovirus type 5 (Ad5-N) and pCDNA3.1 myc/His A (pCD-N1), two widely used vaccine platforms. All constructs expressing viral nucleocapsid (N) protein successfully elicited cytokine and total/specific antibody responses in BALB/c mice. BoHV4-∆TK-CCHFV-N and Ad5-N constructs further produced 100% protection in IFNAR^-/- mice during CCHFV Ank-2 strain lethal challenge. Despite elevated specific antibody responses in both animal models, the produced antibodies were unable to neutralize the virus in vitro. A comparison of delivery platforms was not possible, due to similar protection rates in IFNAR^-/- mice. In conclusion, vector-based CCHFV N protein expression proved to constitute an effective approach for the vaccine development pipeline and BoHV-4 emerged as a strong alternative to previously-used virus vectors.

Introduction: The objectives of this study were to (1) investigate the association between human blood type and COVID-19 infection in both inpatient and longitudinal populations at our institution in South Florida and (2) identify the association between blood type and severity of COVID-19 infection via presence of cellular biomarkers of severe infection in hospitalized individuals. Methods: This study consists of (1) a single-center retrospective analysis of 669 of 2,741 COVID-19 positive screened patients seen from January 1, 2020 until March 31, 2021 at the University of Miami Emergency Department (ED) who tested positive for COVID-19 infection and had a documented ABO blood type and (2) a longitudinal SARS-CoV-2 immunity study (“CITY”) at the University of Miami Miller School of Medicine consisting of 185 survey participants. COVID-19 outcome rates and 95% confidence intervals were calculated for each ABO blood type and Rh group using Chi-squared tests for categorical and ANOVA for continuous variables in the inpatient cohort and Chi-squared tests for the longitudinal cohort, all executed in R studio. Results: Our inpatient cohort had a mean age of 53.6 (± 17.9) years with 48% males and 52% females. When compared to patients with other blood types, those with O- demonstrated less risk of developing COVID-19 pneumonia (26.7% for O- vs. 69.2% for type A-, 56.5% for A+, 71.4% for AB+, 53.7% for B+, 51.5% for O+, p-value= 0.003 via Chi-squared test) and decreased mortality due to COVID-19 infection (17.0% mortality for O vs. 26.3% for A, 29.2% for B, p-value= 0.012 via Chi-squared test). Blood type O- demonstrated less elevated levels of LDH than did other blood types (p-value= 0.001, ANOVA) and a higher frequency of clinically accepted baseline levels of troponin (0.04 ng/mL) (p-value= 0.026, ANOVA) (Figure 1). Most of the longitudinal cohort was ABO blood grouping type O (47% (87/185)), with 33.5% type A, 14.1% B, and 5.4% AB. Most individuals were Rh positive (85.9%). There was no significant association found between COVID status (infection vs. non-infection) and ABO (Chi-squared test (3, N = 185) = 1.8, p = 0.6) or Rh (Chi-squared test (1, N = 185) = 0.16, p = 0.7) blood typing. Nearly all participants had been vaccinated (95.1% (176/185)), with a majority reporting primary vaccination with Pfizer (57.8% (107/185)), followed by Moderna (33% (61/185)), and Johnson & Johnson (4.3% (8/185)). 8 participants (4.3%) were unvaccinated. Conclusions: In an inpatient setting, blood type O sustained less risk of COVID-19 mortality and O- demonstrated less risk of developing COVID-19 pneumonia. In a longitudinal setting, there was no association found between blood type and COVID-19 severity. As the novelty of COVID-19 infection declines with time, further studies on risk-stratification by blood type are encouraged.

The Yangtze River is cross-linked with numerous lakes within its floodplain and is a worldwide biodiversity hotspot. There is no evidence indicating when this unique river-lake system developed. The endemic East Asian cyprinid clade has evolved diverse spawning adaptations to different flow conditions. Our ancestral egg-type reconstruction showed an ancestral state of adhesive eggs and later demersal eggs origination (both stream adaptations). Semi-buoyant eggs emerged ~18 Mya as a fast-flowing river adaptation, with increased hydration via three yolk protein degradation pathways, ion transport pathways and egg envelope permeability transition pores. Adhesive eggs evolved secondarily ~14 Mya with the egg envelope increasing to four layers and an adhesive layer, along with an increase in adhesiveness via microfilament/adhesive-related protein crosslinking and enhanced glycosaminoglycan biosynthesis, improving adherence to submerged lake plants, indicating that the cross-linked river-lake system formed in the mid-Miocene. This study provides a unique biological evidence for large-scale water system evolution.

Mountain systems within the Mediterranean region, e.g. the Pyrenees, are very sensitive to climate change. In the present study, we quantified the magnitude of extreme precipitation events and the number of days with torrential precipitation (daily precipitation ≥ 100 mm) in all the rain gauges available in the Pyrenees for the 1981-2015 period, analyzing the contribution of the synoptic scale in this type of events. The easternmost (under the Mediterranean influence) and north-westernmost (under Atlantic influence) areas of the Pyrenees registered the highest number of torrential events. The heaviest events are expected in the eastern part, i.e. 400 mm day-1 for a return period of 200 years. Northerly advections over the Iberian Peninsula, which present a low zonal index, i.e. im-plying a stronger meridional component, give rise to torrential events over the western Pyrenees; and easterly advections favour extreme precipitation over the eastern Pyrenees. The air mass travels a long way, from the east coast of North America, bringing heavy rainfall to the western Pyrenees. In the case of the torrential events over the eastern Pyrenees, the air mass causing the events in these areas is very short and originates in the Mediterranean Basin. The NAO index has no influence upon the occurrence of torrential events in the Pyrenees, but these events are closely related to certain Mediterranean teleconnections such as the WeMO

This article examines experiments with elastic material, specifically the deformation of an elastic tube under hydrostatic pressure with a constant flow of fluid inside. This flow induces a pulsatile movement within the elastic tube. Preliminary results are compared with a theoretical model that combines longitudinal and transverse waves. During the experiment, images at various stages of deformation were captured and analyzed. The objective is to better understand the behavior of elastic materials under these conditions and validate the proposed theoretical model through detailed experimental observations, providing a deeper insight into the dynamics of deformation in deformable materials.

Achieving glycemic control and sustaining functional pancreatic β-cell activity remains an unmet medical need in the treatment of type 2 diabetes mellitus (T2DM). Glucokinase activators (GKAs) constitute a class of anti-diabetic drugs designed to regulate blood sugar levels and enhance β-cell function in patients with diabetes. A significant progression in GKA development is underway to address the limitations of earlier generations. Dorzagliatin, a dual-acting GKA, targets both the liver and pancreas and has successfully completed two Phase III trials, demonstrating favorable results in diabetes treatment. The hepato-selective GKA—TTP399— emerges as a strong contender, displaying clinically noteworthy outcomes with minimal adverse effects. This paper seeks to review the current literature, delve into the mechanisms of action of these new-generation GKAs, and assess their efficacy and safety in treating T2DM based on published pre-clinical studies and clinical trials.

Selenoproteins are a group of proteins containing selenium in the form of selenocysteine (Sec, U) as the 21st amino acid coded in the genetic code. Their synthesis is dependent on dietary selenium uptake and a common set of cofactors. Selenoproteins accomplish diverse roles in the body and cell processes by acting, for example, as antioxidants, modulators of the immune function, detoxification agents for heavy metals, and other xenobiotics, key compounds in thyroid hormone metabolism. Although the functions of all this protein family are still unknown, several disorders in their structure, activity or expression have been described by researchers. They concluded that selenium or cofactors deficiency, on one hand, or the polymorphism in selenoproteins genes and synthesis, on the other hand, are involved in a large variety of pathological conditions, including type 2 diabetes, cardiovascular, muscular, oncological, hepatic, endocrine, immuno-inflammatory, neurodegenerative diseases. This review is focused on specific roles in medicine only of selenoproteins that are each named after an alphabet letter, less known than the rest of them, regarding their implications in patho-logical processes of several prevalent diseases and also in disease prevention.

Background: The therapeutic benefits of fermented foods in the treatment and prevention of Type 2 diabetes mellitus have been reported. Aim: Inhibitory effect of fermented rice beverages on α-amylase, α-glucosidase and pancreatic lipase was evaluated. Method: Two fermented rice beverages-fermented rice alone (FKR) and fermented rice plus roasted peanuts (FKRG) were produced using spontaneous fermentation. Capacity of the beverages to inhibit al-pha-glucosidase, alpha-amylase and pancreatic lipase in vitro was evaluated and compared with standards (positive controls). Results: FKR exerted inhibition of α-glucosidase between 9.23-21.11% and FKRG 1.11-17.36% at the various concentrations respectively, with both samples showing the most significant inhibition (about 20%) at 125 μg/mL. FKRG exhibited greater alpha-amylase inhibition activity than FKR, but for both samples, the most significant (P < 0.05) inhibition occurred at 500 μg/mL. With pancreatic lipase, no significant inhibition was observed for both FKR and FKRG at the tested concentrations compared to Orlistat used as control; how-ever, at 31.25 μg /mL FKRG showed an inhibitory effect of approximately 15%, which was not evident at higher concentrations. Conclusion: Low to moderate inhibition of α-amylase, α-glucosidase and pancreatic lipase by both FKR and FKRG, showed that the fermented rice beverages have potential to modulate hyperglycemia in type 2 diabetes in vitro. This is an indi-cation that fermented rice beverage could prevent postprandial hyperglycemia in vivo.

The syntheses of four novel syn-type tricyclic laddersiloxanes bearing eight or six alkenyl groups are presented. These compounds possess reactive alkenyl groups on both the bridged and side silicon atoms and their structures were determined by characterization using multinuclear NMR spectroscopy, mass spectrometry, and elemental analysis techniques. To investigate their reactivity, compounds were subjected to hydrosilylation using two different silanes, and the resulting fully hydrosilylated compounds were analyzed thoroughly. Remarkably, all the synthesized laddersiloxanes displayed high thermal stability, suggesting their potential as promising precursors for the development of new hybrid materials. Additionally, preliminary findings indicate the possibility of exploiting the reactivity difference between the alkenyl groups attached to the D- and T-unit silicon atoms for the synthesis of Janus molecules. These findings highlight the potential of the reported compounds as valuable building blocks in the construction of innovative materials.

Diabetes may cause an increase blood levels of cytokines inducing a rising of C reactive protein (PCR) and fibrinogen stimulating a subclinical inflammation which lead to adhesive molecules expression and to endothelial disfunction. A comprehensive panel of type 1 diabetes mellitus (T1DM) interleukins polymorphisms is not provided yet. As chronic periodontitis (CP) is considered the sixth complication of DM, a clarification is needed about the inflammatory role managed by single nucleotides polymorphisms (SNPs). The goal of this review is to focus on the significant diversity of SNPs in T1DM patients with and without CP. After a digital search on PubMed and Scopus with reference to the last 5 years, 21 items were enrolled. Several ILs were analyzed. T1DM still needs to be thoroughly explored regarding the ILs polymorphisms panel, however the last 5 years have led to the increased independence of this condition, causing autonomous inflammatory effects which requires further investigations. CP and T1DM association in children and adolescents represents a severe gap in literature that should be filled, the scarce presence of studies also about adults serves as a motivation for ulterior clinical researches