In spite of its incidence on pistachio trees, the chemical ecology of Labidostomis lusitanica (Germar) (Coleoptera: Chrysomelidae) has been neglected so far. In this work we provide the first evidence of a biologically active male-specific compound that may be promoting field aggregation. Headspace collections by solid-phase microextraction from feral males and females reported the presence of 2-isobutyl-3-methoxypyrazine exclusively on males. Electroantennographic recordings revealed that males and females responded in a dose-dependent manner to increasing stimuli of 2-isobutyl-3-methoxypyrazine, with females overall displaying a higher response than males. In dual-choice tests, both males and females showed a significant preference for the compound in comparison to a pure air stimulus. In the light of these results, the possible role of 2-isobutyl-3-methoxypyrazine as an aggregation cue in L. lusitanica is discussed.

We conducted a retrospective observational study to assess the hospitalization rates for acute exacerbations of asthma and/or COPD during the first imposed lockdown in Athens, Greece. Patient characteristics and the concentration of eight air pollutants (namely, CO, NO, NO2, O3 PM2.5, PM10, SO2 and benzene) were considered. A total of 153 consecutive hospital admissions were studied. Reduced admissions occurred in the lockdown period when compared to the Pre-lockdown 2020 (p<0.001) or the Control 2019 (p=0.007) period. Furthermore, the concentration of 6/8 air pollutants positively correlated with weekly hospital admissions in 2020 and significantly decreased during the lockdown. Finally, admitted patients for asthma exacerbation during the lockdown were younger (p=0.046) and less frequently presented respiratory failure (p=0.038), whereas patients with COPD presented higher blood eosinophil percentage (p=0.017) and count (p=0.012). Overall, admissions for asthma and COPD exacerbations decreased during the lockdown. This might partially explained by reduction of air pollution during this period while medical care avoidance behavior, especially among elderly patients cannot be excluded. Our findings aid in understanding the untold impact of the pandemic on diseases beyond COVID-19, focusing on patients with obstructive diseases..

With the onset of the COVID19 pandemic, information technology has played a critical role in healthcare. A broad spectrum of information technology tools and applications played an essential role to create awareness of the COVID19 vaccination drive and its health benefits. We use the COVID-19 Global Beliefs, Behaviors, and Norms Survey for analysis of prevalence and factors associated with vaccination drives among men and women aged 20-80 years in 60 countries worldwide. Our analysis of the global survey offers a unique perspective about the role of information technology associated with vaccination drives involving social norms and human behavior among 437,236 respondents. The international survey was organized using a pre-registered randomized experiment demonstrating the role of technology in reaching out to people based in diverse communities and evaluating their beliefs, behavior, and social norms. The study shows that vaccine acceptance can vary due to descriptive norms. Our analysis shows 65.06% of people all over the globe are willing to get vaccinated and a large proportion of the population thinks that the COVID19 pandemic is a viable threat to the community and preventive measures need to be taken including vaccination drives.

The Hunga Tonga-Hunga Ha’apai underwater volcano (20.57°S, 175.38°W) violently erupted on 15 January 2022. The volcanic plume evolution during its initial stages is delineated by using Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC)-2 radio occultation (RO) measurements. The bending angle (BA) anomaly over the Tonga volcanic plume (within 200 km from the eruption center) at 5:17 UTC on 15 January shows a prominent peak at higher stratospheric heights. The top of the BA anomaly revealed that negative to positive change occurred at ~38 km indicating the first height where the RO line-of-sight encounters the volcanic plume. The BA anomaly further revealed an increase of ~50% at ~36 km and confirms the volcanic plume reached above ~36 km. Further, the evolution of BA perturbations within 24 hours after the initial explosion is also discussed. From collocated RO profiles with the volcanic plume, we find a clear descending of the peak altitude of the BA perturbation from ~36 km to ~30 km within 24 hours after the initial eruption. The results from the study will provide some insights into advancing our understanding of volcanic cloud dynamics and their implementation in volcanic plume modeling.

Typical 2-Cys peroxiredoxins (2-Cys Prdxs) are proteins with antioxidant properties belonging to the thioredoxin peroxidase family. With their peroxidase activity, they contribute to the homeostatic control of reactive oxygen species (ROS) and, therefore, participate in various physiological functions such as cell proliferation, differentiation, and apoptosis. Although Prdxs have been shown to be potential biomarkers for monitoring the aquatic environments, minimal scientific attention has been devoted to describing their molecular architecture and function in marine invertebrates. Our study aims to clarify the protective role against stress induced by exposure to metals (Cu, Zn, and Cd) of three Prdxs (Prdx2, Prdx3, and Prdx4) in the solitary ascidian Ciona robusta, an invertebrate chordate. Here we report a detailed pre- and post-translational regulation of the three Prdx isoforms. Data on intestinal mRNA expression, provided by qRT-PCR analyses, show a generalized increase for Prdx2, 3, and 4, which is correlated to metal accumulation. Furthermore, the increase in tissue enzyme activity observed after Zn exposure is slower than that observed with Cu and Cd. The obtained results increase our knowledge of the evolution of anti-stress proteins in invertebrates and emphasize the importance of the synthesis of Prdxs as an efficient way to face adverse environmental conditions.

The C-type lectin-like receptor 2 (CLEC-2) is expressed on platelets and mediates binding to podoplanin (PDPN) on various cell types. The binding to circulating tumor cells (CTCs) leads to platelet activation and promote metastatic spread. The increased level of soluble CLEC-2 (sCLEC-2), presumably, released from activated platelets was shown in patients with thromboinflammatory and malignant disease. However, the functional role of sCLEC-2 and the mechanism of sCLEC-2 release is not known. In this study, we focused on the effect of platelet activation on CLEC-2 expression and the sCLEC-2 plasma level in cancer patients. First, citrated blood from healthy volunteer donors (n=20) was used to measure the effect of platelet stimulation by classical agonists and PDPN on aggregation, CLEC-2 expression on platelets by flow cytometry, sCLEC-2 release to the plasma by ELISA and total CLEC-2 expression by Western blot analysis. Second, sCLEC-2 was determined in plasma samples from healthy donors (285) and patients with colorectal carcinoma (CRC; 194), melanoma (160), breast cancer (BC; 99) or glioblastoma (49). PDPN caused a significant increase of the aggregation response induced by classical agonists. ADP or PDPN stimulation of platelets caused a significant decrease of CLEC-2 on platelets and sCLEC-2 in the plasma, whereas, total CLEC-2 in platelet lysates remained the same. Thus, the increased plasma level of sCLEC-2 is not a suitable biomarker of platelet activation. In patients with CRC (median 0.9 ng/mL), melanoma (0.9 ng/mL) or BC (0.7 ng/mL) we found significantly lower sCLEC-2 levels (p<0.0001), whereas, glioblastoma patients displayed higher levels (2.6 ng/mL; p=0.0233) compared to healthy controls (2.1 ng/mL). The low sCLEC-2 plasma level observed in most of the tumor entities of our study, presumably, results from the internalization of sCLEC-2 by activated platelets or binding of sCLEC-2 to CTC.

Reservoirs created by damming rivers significantly modify the environment and problems may arise: the storage of nutrients and organic matter in reservoirs often leads to decreased water quality due to eutrophication. Reservoirs built on lowland rivers are exposed to significant nutrient loads, often leading to eutrophication. In this article, the Sulejów Reservoir, in Central Poland, was the subject of the research, which focused on the use of Sentinel-2 remote sensing data to detect phytoplankton blooms, and on understanding the pattern of wind-driven surface currents using the CCHE2D model (a depth-averaged hydrodynamic model). The calculation of the total phosphorus load has shown that the reservoir mainly acts as nutrient storage. Still, during the low flow and intensive phytoplankton bloom, it can be a source of nutrients. The distribution of phytoplankton bloom on the Sulejów Reservoir was documented using eight Sentinel-2 satellite images from the vegetation season of 2020 and the Normalized Difference Chlorophyll Index (NDCl). Coupling remote sensing data and numerical modelling helps to interpret the hydrodynamic model results and understand nutrients and sediment dynamics within the reservoir. Hydrodynamic modelling combined with remote sensing data can be a valuable tool for selecting appropriate locations for water quality measurements at monitoring stations.

In order to comprehensively evaluate the employee satisfaction of mine occupational health and safety management system, an analytic method based on fuzzy analytic hierarchy process and 2- tuple linguistic model was established. Firstly, based on the establishment of 5 first- grade indicators and 20 second- grade ones, the weight of each indicator is calculated and validated by method of FAHP and root mean square model. Secondly, a path based on the time-ordered Weighted Averaging Operator (T-OWA) model is constructed. Finally, the model is validated by empirical analysis. The results demonstrate that the employee satisfaction of the mine occupational health and safety management system is of the “general” rank. The method including the comprehensive evaluation of employee satisfaction and the quantitative analysis of language evaluation information ensures the authenticity of the language evaluation information.

Byers Peninsula is considered one of the largest ice-free areas in Maritime Antarctica. Since 2006, the Spanish Polar Program has taken part in a large number of environmental studies involving effects of climate changes in lives cycles, limnology and microbiology. Soils from maritime Antarctica are generally weakly developed and have chemical, physical and morphological characteristics strongly influenced by the parent material. However, biological activity during the short Antarctic summer promotes intense transference of nutrients and organic matter in areas occupied by different species of birds and marine mammals. To mapping and monitoring those areas with high biological occupation, could be very useful to have models of edaphic properties prepared from satellite images. In this approach, Deep Learning and Linear Regression models of soil properties and spectral indexes as explicative variables were performed. We training models of soil properties closely related to biological activity such as Dissolved Organic Carbon (DOC) and the iron fraction associated with organic matter (Fe). We tested the best approach to model the spatial distribution of DOC, Fe and pH by training models of Linear Regression and Deep Learning over Sentinel2 and WorldView2 images. The most robust models were used to track possible areas with ornithogenic soils as well as areas of the Byers Peninsula that could support the highest biological development.

Developing nanomaterials with the capacity to restrict the growth of bacteria and fungus is of current interest. In this study, nanocomposites of poly(2-hydroxyethyl methacrylate) (PHEMA) and carbon nanotubes (CNTs) functionalized with primary amine, hydroxyl, and carboxyl groups were prepared, and characterized. An analysis by Fourier transform infrared (FT-IR) spectroscopy and X-ray photoelectron spectroscopy showed that PHEMA chains were grafted to the functionalized CNTs. The morphology of the prepared nanocomposites studied by field emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM) shows significant changes with respect to the observed for pure PHEMA. The thermal behavior of the nanocomposites studied by differential scanning calorimetry (DSC) revels that the functionalized CNTs affects strongly the mobility of the PHEMA chains. Tests carried out by thermogravimetric analysis (TGA) were used to calculate the degree of grafting of the PHEMA chains. The ability of prepared nanocomposites to inhibit the growth of the fungus Candida albicans, and the bacteria Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli was evaluated. A moderated antifungal and antibacterial capacity of the prepared nanocomposites was determined.

A human case of dengue virus 2 was detected from a febrile patient living in the Sare yoba, Kolda region (Southern Senegal). Phylogenetic analysis based on the partial sequence of the NS5 gene reveals that the virus belongs to the DENV2 Sylvatic genotype and is closely related to a strain (JF260983/ 98.98% identity) detected in Spain from a tourist who travelled to Guinee Bissau (bordering Kolda region) in 2009. This highlights a potential recent underreported circulation of sylvatic Dengue in the southern part of Senegal and calls for re-enforced integrated surveillance among humans, non-human primates and arboreal mosquitoes throughout a one-health approach.

Revealing the time structure of physical or biological objects is usually performed thanks to the tools of signal processing like the fast Fourier transform, Ramanujan sum signal processing and many other techniques. For space-time topological objects in physics and biology, we propose a type of algebraic processing based on schemes in which the discrimination of singularities within objects is based on the space-time-spin group SL(2,C). Such topological objects possess an homotopy structure encoded in their fundamental group and the related SL(2,C) multivariate polynomial character variety contains a plethora of singularities somehow analogous to the frequency spectrum in time structures. Our approach is applied to an Akbulut cork in exotic R4, to an hyperbolic model of topological quantum computing based on algebraic surfaces and to microRNAs in genetics. Such diverse topics reveal the manifold of possibilities of using the concept of a scheme spectrum.

Type 2 diabetes mellitus (T2DM) poses a significant economic and clinical burden. Clinical inertia is defined as the failure of healthcare providers to modify therapy in the presence of clear indications. This study aimed to identify patient opinions on insulin to understand the barriers preventing type 2 diabetes patients from initiating insulin treatment when recommended by their physician. This cross-sectional observational study included 671 individuals with poorly controlled T2DM and HbA1c levels exceeding 10%. These patients required either the initiation or escalation of their existing insulin therapy. The participants were referred to Thi-Qar Specialized Diabetes Endocrine and Metabolism Center (TDEMC) for consultation between January 2022 and July 2022.Results: During discussions between the researcher (clinician) and the inadequately controlled T2DM patients, the primary reasons for refusing insulin therapy were identified. These reasons included fear of injections, the belief that insulin induces dependence and is a last resort, concerns about hypoglycemia and complications, cost, difficulty in computing doses, social stigma, inconvenience and disruption to life and work, storage challenges, fear of weight gain, dependence on others, and lack of confidence.The study concludes that the clinical barriers faced by individuals who refuse the initiation of insulin therapy are diverse. The most common belief among the patients was that insulin leads to dependence (38%), while the smallest percentage cited a lack of confidence in insulin as an effective treatment for lowering hyperglycemia.

Background: Mounting evidence supports the role of the endocannabinoid system in neurophysiology, includ-ing blood-brain barrier (BBB) function. Recent work has demonstrated that activation of endocannabinoid re-ceptors can mitigate insults to the BBB during neurological disorders, like traumatic brain injury, cortical spreading depression and stroke. As alterations to the BBB are associated with worsening clinical outcomes in these conditions, studies herein sought to examine the impact of endocannabinoid depletion on BBB integrity. Methods: Barrier integrity was investigated in vitro via bEnd.3 cell monolayers to assess endocannabinoid syn-thesis, barrier function, calcium influx, junctional protein expression, and proteome-wide changes. Results: In-hibition of 2-AG synthesis using DAGLα inhibition and siRNA inhibition of DAGLα led to loss of barrier in-tegrity via altered expression of VE-cadherin, which could be partially rescued by exogenous application of 2-AG. Moreover, the deleterious effects of DAGLα inhibition on BBB integrity showed both calcium and PKC (protein kinase C)-dependency. Conclusions: These data indicate that disruption of 2-AG homeostasis in brain endothelial cells, in the absence of insult, is sufficient to disrupt BBB integrity thus supporting the role of the endocannabinoid system in neurovascular disorders.

Various optically active 2-hydroxyamide derivatives are produced based on the kinetic resolution of racemic 2-hydroxyamides with a diphenylacetyl component and (R)-benzotetramisole [(R)-BTM], a chiral acyl-transfer catalyst, via asymmetric esterification and acylation. It was revealed that a tertiary amide can be used with this novel protocol to achieve high selectivity [22 examples; s-value reaching over 250]. The resulting chiral compounds could be transformed into other useful structures while maintaining their chirality.

The increasing concern regarding climate change continues to motivate research in the Arctic. Within the delicate cycle of the cryosphere, leads are an important kinematic feature that regulate heat balances in the Arctic. Therefore, it is necessary to quantify the genesis of leads over time to identify when and where changes are occurring. The use of a principal component analysis (PCA) is one such tool that is used to identify the characteristics of seasonal ice variability. The PCA not only identifies “normal” or “dominant” conditions or features, but also extract anomalous spatial features from an archive of long-term sequence of images.

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.

This research intended to report amine-functionalized multiwall carbon nanotubes (MWCNTs) prepared by a simple method for efficient and rapid removal of Reactive Yellow 2 (RY2) from water. EDS analysis showed that the N content increased from 0 to 2.42% and from 2.42 to 8.66% after modification by APTES and PEI, respectively. BET analysis displayed that the specific surface area, average pore size, and total pore volume were reduced from 405.22 to 176.16 m2/g, 39.67 to 6.30 nm, and 4.02 to 0.28 cm3/g, respectively. These results proved that the PEI/APTES-MWCNTs were successfully prepared. pH edge experiment indicated that pH 2 was optimal for RY2 removal. At pH 2 and 25 °C, the time required for adsorption equilibrium was 10, 15, and 180 min at initial concentrations of 50, 100, and 200 mg/L, respectively; and the maximum RY2 uptake calculated by the Langmuir model was 714.29 mg/g. Thermodynamic studies revealed that the adsorption process was spontaneous and endothermic. 0-0.1 mol/L of NaCl showed negligible effect on RY2 removal by PEI/APTES-MWCNTs. Five adsorption/desorption cycles confirmed the good reusability of PEI/APTES-MWCNTs in RY2 removal. Overall, the PEI/APTES-MWCNTs are a potential and efficient adsorbent for reactive dye wastewater treatment.

Proper satellite-based crop monitoring applications at the farm-level often require near-daily imagery at medium to high spatial resolution. The synthesizing of ongoing satellite missions by ESA (Sentinel 2) and NASA (Landsat7/8) provides this unprecedented opportunity at a global scale; nonetheless, this is rarely implemented because these procedures are data demanding and computationally intensive. This study developed a complete stream processing in the Google Earth Engine cloud platform to generate harmonized surface reflectance images of Landsat7,8 and Sentinel 2 missions. The harmonized images were generated for two agriculture schemes in Bekaa (Lebanon) and Ninh Thuan (Vietnam) during the period 2018-2019. We evaluated the performance of several pre-processing steps needed for the harmonization including image co-registration, brdf correction, topographic correction, and band adjustment. This study found that the miss-registration between Landsat 8 and Sentinel 2 images, varied from 10 meters in Ninh Thuan, Vietnam to 32 meters in Bekaa, Lebanon, and if not treated, posed a great impact on the quality of the harmonized dataset. Analysis of a pair overlapped L8-S2 images over the Bekaa region showed that after the harmonization, all band-to-band spatial correlations were greatly improved from (0.57, 0.64, 0.67, 0.75, 0.76, 0.75, 0.79) to (0.87, 0.91, 0.92, 0.94, 0.97, 0.97, 0.96) in bands (blue, green, red, nir,swir1,swir2, ndvi) respectively. We demonstrated that dense observation of the harmonized dataset can be very helpful for characterizing cropland in highly dynamic areas. We detected unimodal, bimodal and trimodal shapes in the temporal NDVI patterns (likely cycles of paddy rice) in Ninh Thuan province only during the year 2018. We fitted the temporal signatures of the NDVI time series using harmonic (Fourier) analysis. Derived phase (angle from the starting point to the cycle's peak) and amplitude (the cycle's height) were combined with max-NDVI to generate an R-G-B image. This image highlighted croplands as colored pixels (high phase and amplitude) and other types of land as grey/dark pixels (low phase/amplitude). Generated harmonized datasets that contain surface reflectance images (bands blue, green, red, nir, swir1, swir2, and ndvi at 30 meters) over the two studied sites are provided for public usage and testing.

This paper presents a new method for the design of separable denominators 2-D IIR filters with nearly linear phase in the passband. The design method is based on a balanced-realization model reduction technique. The nearly linear-phase 2-D IIR filter is designed using 2-D model reduction from a linear-phase 2-D FIR filter, which serves as the initial filter. The structured controllability and observability Gramians $P^s$ and $Q^s$ serve as the foundation for this technique. These Gramians are block diagonal positive-definite matrices that satisfy 2-D Lyapunov equations. An efficient method is used to compute these Gramians by minimizing the traces of $P^s$ and $Q^s$ under linear matrix inequalities (LMI) constraints. The use of these Gramians ensures that the resulting 2-D IIR filter preserves stability and can be implemented using a separable denominator 2-D filter with fewer coefficients than the original 2-D FIR filter. Numerical examples show that the proposed method compares favorably with existing techniques.

The uneven immunogenicity of the attenuated tetravalent dengue vaccine has created the diffi-culty to achieve a balanced protection against all four serotypes of dengue virus (DENV). To overcome this problem, non-replicative-based vaccines have come into focus as their immuno-genicity is adjustable. This approach is excellent for multivalent vaccines but commonly faces the issue of low immunogenicity. In this present study, we developed a non-replicating dengue vaccine composing of UV-inactivated dengue-2 virus (UV-DENV2) and DENV-2 NS1-279 protein encapsidated within nanoparticles. This vaccine candidate was administered in the presence of BCG cell wall cytoskeleton (BCG-CWS) as an adjuvant. We revealed, here, that encapsidated immunogens with BCG-CWS exerted potent activities on both B and T cells and elicited Th-1/Th-2 responses in mice. This was evidenced by strong neutralizing antibody activity with an unde-tectable antibody enhancing activity in a group of mice receiving encapsidated immunogens with BCG-CWS. Importantly, BCG-CWS significantly augmented antibody-mediated comple-ment-fixing activity, strongly stimulated the antigen-specific polyfunctional T cell responses as well as activated mixed Th-1/Th-2 responses specific to DENV2- and NS1-279 antigens. In conclu-sion, BCG-CWS potently adjuvanted the inactivated DENV-2 and subunit DENV immunogens. The mechanism of adjuvanticity remains unclear. This study revealed the potential use of BCG-CWS in vaccine development.

Escherichia coli and Shigella are common diarrhea-causing pathogens in children and adults. Enteroinvasive Escherichia coli (EIEC) shares a similar pathogenic mechanism with Shigella. However, EIEC are less virulent than Shigella. The aim of this work was to get a better understanding of the virulence differences between EIEC and S. flexneri. We investigated i) the bacterial gene co-expression networks (GCNs) and ii) the the transcriptional modules (WGCNA) of Caco-2 cells infected with EIEC or with S. flexneri during a three-hour period of bacterial infection. The GCN analysis showed that EIEC and S. flexneri networks presented different topologies. Additionally, the EIEC network revealed that pINV genes are not connected with chromosomal genes. WGCNA and eigengene analysis showed enterocyte gene expression variation along the three-hour bacterial post-infection period. Additionally, at one-hour post-infection EIEC induced a higher number of gene expression changes in Caco-2 cells than S. flexneri. Several of these genes are involved in autophagy. This study showed that the lower virulence of EIEC is associated with a lack of functional cooperation between pINV and chromosomal genes, differently from what was observed in S. flexneri. Consequently, EIEC becomes less efficient in subverting host-cell bacterial recognition as well as defense mechanisms such as autophagy.

Supplier selection is one of the most important multi criteria decision making (MCDM) problems for decision makers in competitive market. Organizations of today’s world are seeking new ways to reduce negative effects of their organizations to the environment and to reach a greener system. At this point, green supplier selection concept has gained great importance with its ability on incorporating environmental or green criteria into the classical supplier selection practices. Therefore, in this study, it is aimed at proposing a multi-phase MCDM model based on Best-Worst Method (BWM) and interval type-2 fuzzy technique for order preference by similarity to ideal solution (TOPSIS). A case study in a plastic injection molding facility in Turkey is performed to show the applicability of the proposed integrated methodology. The paper ensures insights into the decision making, methodology, and managerial implications. Results of the case study are examined and suggestions for future research are provided.

For more than ten years, Central Chile faces drought conditions, which impact crop production and quality, increasing food security risk. Under this scenario, implementing management practices that allow increasing water use efficiency is urgent. The study was carried out in kiwifruit trees, located in the O’Higgins region, Chile; for season 2018-2019 and 2019-2020. We evaluate nine vegetation indices in the VNIR and SWIR regions derived from Sentinel-2 (A/B) satellites to know how much variability in the canopy water status could explain. Over the study's site were installed sensors that continuously measure the leaf's turgor pressure (Yara Water-Sensor). A strong correlation between turgor pressure and vegetation indices was obtained with the Spearman's rho coefficient ($\rho$). However, the NIR range's indices were influenced by the vegetative development of the crop rather than its water status. Red-edge showed better performance as the vegetative growth did not affect it. It is necessary to expand the study to consider higher variability in kiwifruit's water conditions and incorporate the sensitivity of different wavelengths.

We describe the innate and adaptive immune system trajectory in Multi-system inflammatory syndrome of childhood (MIS-C), at acute(within 72 hours of hospitalization), resolution (at clinical improvement) and convalescent phase. In our cohort, in the acute phase, 68% of the children were SARS-CoV-2 seropositive, with hypercytokinenemia (high interleukin(IL)-1beta,IL-6,IL-8,IL-10,IL-17, interferon gamma), procoagulant state, myocardial dysfunction, activated neutrophils and monocytes; differential T and B cell subset lymphopenia; activated chemokine receptor type-7 positive and gamma-delta T cell subsets; antigen presenting cells had reduced HLA-DR expression; and B-cell class-switch responses occurred with illness resolution. MIS-C is an immunopathogenic illness associated with SARS-CoV-2 infections in children.

Diabetes mellitus – type 2 (DM2) is a hypercoaguable state with enhanced platelets (PLTs) activation and increased clotting factor production. Simultaneously, the fibrinolytic cell system is inhibited due to formation of clots with high resistance to fibrinolysis. The stages of PLTs "activation" have been well-characterized microscopically, morphometrically and nanomechanically (by light microscope, transmisiion electron microscope - TEM, scanning electron microscope - SEM and atomic force microscope - AFM). Thrombocytes in "acivated" (pro-coagulant) state play central role in two main biological processes: hemostasis and repair of vascular vessels. Pro-coagulant PLTs participate in generation of thrombin and in development of fibrin fibers in the clot matrix. Enhanced PLTs reactivity in dibetic- (diabetes mellitus - DM2) patients is considered as a "pro-thrombotic" state. In the retrospective- and prospective- studies on the topic, the higher are the PLTs' hematometrical indices: PLTs (count), MPV (mean platelet volume), PDW (platelet distribution width), PCR (plateletcrit), as well as PLTs/Ly ratio. The PLТs parameters/indices are usefull biomarkers in early diagnosis and prognosis of DM2. The precise studies of PLTs' state of activation during DM2 might be useful for creation of new diabetes (DM2) treatment strategies and effective medicines. Using the amount of blood glucose, attached to hemoglobin (HbA1c values) as markers of glycemic control in diabetic patients, researchers have observed association between MPV and medications as Insulin, Metformin, sulphonyl ureas. Computational modellng of PLTs' activation in DM2 is also a controlling factor for thrombocyte distribution and margination in bood vessels, associated with micro- and macrovascular disease in DM2. PLTs-derived miRNAs are novel molecular biomarkers for diagnosis and prognosis of DM2, insulin resistance and diabetes complications. We have proposed (2010) oleic acid (OA) as a substance suppressing "PLT hyperactivation" and inhibiting “thrombocyte aggregation”. Antiplatelet agents, natural plant products including, could be effective in the prevention and the secondary treatment of micro- and macrovascular complications in the type 2 Diabetes mellitus. Our proposal on following up of a combination of hematological-, hemorheological- and hemostatic parameters (indices) as a new way in diagnosis, treatment, predicting and management of DM2 and its related vascular complications, probably could be more explored in future studies.

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.

Background: Green synthesis of silver (Ag) nanoparticle was performed with the fruit extract of Scindapsus officinalis and test against HepG-2, MCF-7 cancer cell lines. These biosynthesized metal nanoparticles have a potential of therapeutic use as an alternative medicine for the treatment of hepatic & breast cancer cases. Results : AgNPs were identified by change of color & their absobtion at 340 nm measured by UV-visible spectroscopy, FTIR spectral analysis confirmed phenolic compounds presence, morphology & size visualized in SEM, TEM used for determination of size, shape & light scattering analysis. Synthesized silver nanoparticles were spherical in shape and size less than 50 nm. XRD analysis was affirmed the crystalline nature of metal particles. In-vitro cytotoxic result showed an excellent IC50 value of 155.81μg/ml and 114.74 μg/ml against HepG-2 & MCF-7 cell lines. Conclusion: The current study reveals green synthesized AgNPs possess high cytotoxic action against HepG-2 & MCF-7 cell lines which suggested the use of silver nanoparticles as a medicine to treat hepatic & breast cancer.

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

Fusarium culmorum is a major pathogen of grain crops. Infected plants accumulate deoxynivalenol (DON), 3-acetyl-deoxynivalenol (3-ADON), or nivalenol (NIV), which are mycotoxins of the trichothecene B group. These toxins are also produced by F. graminearum species complex. New trichothecenes structurally similar to trichothecenes B but lacking the carbonyl group on C-8, designated NX toxins, were recently discovered in atypical isolates of F. graminearum from North America. Only these isolates and a few strains of a yet to be characterized Fusarium species from South Africa are known to produce NX-2 and other NX toxins. Here we report that among 20 F. culmorum strains isolated from maize, wheat, and oat in Europe and Asia over a period of 70 years, 18 strains produced NX-2 simultaneously with 3-ADON and DON or NIV. Rice cultures of strains producing 3-ADON accumulated NX-2 in amounts corresponding to 2-8% of 3-ADON (1.2 - 36 mg/kg). A strain producing NIV accumulated NX-2 and NIV at comparable amounts (13.6 and 10.3 mg/kg, respectively). In F. graminearum, producers of NX-2 possess a special variant of cytochrome P450 monooxygenase encoded by TRI1 that is unable to oxidize C-8. In F. culmorum, producers and nonproducers of NX-2 possess identical TRI1; the reason for the production of NX-2 is unknown. Our results indicate that production of NX-2 simultaneously with trichothecenes B is a common feature of F. culmorum.

Conventional methods of crop mapping need ground truth information to train the classifier. Thanks to the frequent acquisition allowed by recent satellite missions (Sentinel 2), we can identify temporal patterns that depend on both phenology and crop management. Some of these patterns are specific to a given crop and thus can be used to map it. Thus, we can substitute ground truth information used in conventional methods with agronomic knowledge. This approach was applied to identify irrigated permanent grasslands (IPG) in the Crau area (Southern France) which play a crucial role in groundwater recharge. The grassland is managed by making three mows during the May-October period which leads to a specific temporal pattern of leaf area index (LAI). The mowing detection algorithm was designed using the temporal LAI signal derived from Sentinel 2 observations. The algorithm includes some filtering to remove noise in the signal that might lead to false mowing detection. A pixel is considered a grassland if the number of detected mows is greater than 1. A data set covering five years (2016-2020) was used. The detection mowing number was done at the pixel level and then results are aggregated at the plot level. A validation data set including 780 plots was used to assess the performances of the classification. We obtained a Kappa index ranging between 0.94-0.99 according to the year. These results were better than other supervised classification methods that include training data sets. The analysis of land-use changes shows that misclassified plots concern grasslands managed less intensively with strong intra-parcel heterogeneity due to irrigation defects or year-round grazing. Time series analysis, therefore, allows us to understand different management practices. Real land-use change in use can be observed, but long time series are needed to confirm the change and remove ambiguities with heterogeneous grasslands.

Background/Objectives: The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing at an alarming rate. Cardiovascular disease (CVD) is the leading cause of mortality in MASLD patients, therefore, the therapeutic interventions for MASLD should improve coronary risk factors such as obesity, diabetes and dyslipidemia, in addition to improving liver function. The evidence on effect of sodium-glucose cotransporter 2 inhibitors (SGLT2is) which have beneficial pharmacological properties for MASLD, especially the long-term effects, on the progression of MASLD in Asian population is very limited. Methods: The retrospective longitudinal study was performed by using the medical records at the National Center for Global Health and Medicine, Kohnodai Hospital, Japan. We picked up patients with type 2 diabetes who had taken SGLT2is for at least 3 years or longer between April 1, 2014 and March 31, 2018. We collected the data on metabolic parameters, including blood tests and anthropometric parameters, and compared the data before and after the initiation of SGLT2is treatment. Results: During the observation period, 324 patients had taken SGLT2is for 3 years. The 3-year-SGLT2is treatment significantly reduced body weight, hemoglobin A1c, low-density lipoprotein-cholesterol, triglyceride and non-high-density lipoprotein-cholesterol (HDL-C) and significantly increased HDL-C. Furthermore, this treatment significantly improved liver function and the markers for hepatic steatosis and hepatic fibrosis. Conclusions: Considering that the development of CVD determines the prognosis of MASLD patients, the long-term SGLT2is treatment may be an ideal therapy for MASLD patients.

The global prevalence of type 2 diabetes mellitus (T2DM) has surged in recent decades and the identification of differential glycemic responders can aid tailored treatment for prevention of pre-diabetes and T2DM. A mixed meal tolerance test (MMTT) based on regular foods offers potential to uncover differential responders in dynamical postprandial events. We aimed to fit a simple mathematical model on dynamic postprandial glucose data from repeated MMTTs among partic-ipants with elevated T2DM risk, to identify response clusters and investigate their association with T2DM risk factors and gut microbiota. Data were used from a 12-week multi-center dietary inter-vention trial involving high-risk T2DM adults, comparing high- versus low-glycemic index foods within a Mediterranean diet context (MEDGICarb). Model-based analysis of MMTTs from 155 participants (81 females, 74 males) revealed two distinct plasma glucose response clusters that were associated with baseline gut microbiota. Cluster A, inversely associated with HbA1c and waist circumference and directly with insulin sensitivity, exhibited a contrasting profile to cluster B. Findings imply that a standardized breakfast MMTT using regular foods could effectively distin-guish non-diabetic individuals at varying risk levels for T2DM using a simple mechanistic model.

Rapid and continuing advances in biomarker testing are not being matched by take-up in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. The potential that genomics has brought to biomarker testing in diagnosis, prediction and research is being realised, pre-eminently in many cancers, but also in an ever-wider range of conditions. One of the paradigmatic examples is BRCA1/2 testing in ovarian, breast, pancreatic and prostate cancers. Nevertheless, development is impeded by data deficiencies, and lack of policy alignment on standards, approval – and the role of real-world evidence in the process - and reimbursement. The acute nature of the problem is compellingly illustrated by the particular challenges facing the development and use of tumour agnostic therapies, where the gaps in preparedness for taking advantage of this innovative approach to cancer therapy are sharply exposed. Europe should already have in place a guarantee of universal access to a minimum suite of biomarker tests and should be planning for an optimum testing scenario with a wider range of biomarker tests integrated into a more sophisticated health system articulated around personalised medicine. Improving healthcare and winning advantages for Europe's industrial competitiveness and innovation require an appropriate policy framework – starting with an update to outdated recommendations.

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.

Introduction: Type 2 Diabetes mellitus (T2DM) is a common disease burdened with significant morbidity and mortality. Despite the substantial number of new available drug treatments, adherence to therapy and adverse drug reactions (ADRs) are the major constrain in the management of this disease. We evaluated the use, the adherence and the dsaftey of antidiabetic drugs in patients with T2DM. Methods: we performed an observational, retrospective, multicenter study on medical records of outpatients referred to general practitioners. Drug adherence was measured in agreement to the European Society for Patient Adherence, Compliance and Persistence Medication Adherence Reporting Guideline. ADRs were evaluated using the Naranjo probability scale. Collected data were analyzed using the Statistical Package for the Social Sciences. Results: During the study we evaluated 12,170 medical records of 7 general practitioners. The most prescribed drug was metformin alone (28.4%) or with other oral antidiabetics (19.6%) and then insulin (n: 354; men 190, women 164). Enrolled patients were stratified as high (35%), medium (41%) and low (24%) adherence. Logistic regression showed an association between T2DM less than or equal to 5 years and low adherence (P = 0.023). During the study we recorded 26 ADRs that was correlated with sex (women) and insulin treatment. Conclusion: this real-life study shows that patients with T2DM have high adherence probably related dto a low number of ADRs

Gelephu, located in the Himalayan region, has experienced one of the strongest development activities due to the suitable topography and geographic location, which has led to rapid urbanization. The main objective of the study is to perform land use land cover (LULC) mapping for Gelephu for 2016 and 2023 by a Random Forest (RF) classifier, using the Semi-automatic Classification Plugin (SCP) in QGIS and identify LULC changes. Furthermore, the study assessed the vegetation change dynamics within the study area by analysing the Normalized Difference Vegetation Index (NDVI) for 2016 and 2023. Additionally, the study characterized the resulting LULC change for Gelephu Thromde, a sub-administrative municipal entity, as a result of the notable intensity of the infrastructure development activities. The current study used a framework to collect Sentiniel-2 satellite data, which was then used for pre- and post-processing to create LULC and NDVI maps. The classification model achieved high accuracy, with an area under the curve (AUC) of up to 0.89. The corresponding LULC and NDVI statistics were analysed to determine the current status of the LULC and vegetation indices, respectively. The LULC change analysis reveals urban growth of 5.65% and 15.05% for Gelephu and Gelephu Thromde, respectively. The NDVI assessment shows significant deterioration in vegetation health with a 75.11% loss of healthy vegetation in Gelephu between 2016 and 2023. This research provides the first version of LULC and NDVI maps of Gelephu. The analysis results indicate possible future implications on sustainable development management in Gelephu Bhutan.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a serious health problem, and recent evidence indicates that gut microbiota plays a key role in its development. It is known that 2-oleoyl glycerol (2-OG) produced by the gut microbiota is associated with hepatic fibrosis, but it is not known whether this metabolite is involved in the development of hepatic steatosis. The aim of this study was to evaluate how a high-fat sucrose diet (HFS) increases 2-OG production through gut microbiota dysbiosis and to identify whether this metabolite modifies hepatic lipogenesis and mitochondrial activity for the development of hepatic steatosis as well as whether a combination of functional foods can reverse this process. Wistar rats were fed HFS diet for 7 mo. At the end of the study, body composition, biochemical parameters, gut microbiota, protein abundance of lipogenic and antioxidant enzymes, measurement of liver 2-OG, and mitochondrial function were assessed in rats and we studied the effect of HFS with functional foods. In humans with MASLD, we analyzed gut microbiota and serum 2-OG. Consumption of HFS diet in Wistar rats caused oxidative stress, hepatic steatosis and gut microbiota dysbiosis, decreasing α-diversity and increased Blautia producta abundance, which increased 2-OG. This metabolite increased de novo lipogenesis through ChREBP and SREBP-1. 2-OG significantly increased mitochondrial dysfunction. Addition of functional foods to the diet modified the gut microbiota, reducing B. producta and 2-OG levels, leading to a decrease in body weight gain, body fat mass, serum glucose, insulin, cholesterol, triglycerides, fatty liver formation, and increased mitochondrial function. In order to use 2-OG as biomarker, this metabolite was measured in healthy subjects or with MASLD and it was observed that subjects with hepatic steatosis II and III had significantly higher 2-OG than healthy subjects, suggesting that the abundance of this circulating metabolite could be a predictor marker of hepatic steatosis.

The regioselectivity in non-polar [3+2] cycloaddition (32CA) reactions has been studied within the Molecular Electron Density Theory (MEDT) at the B3LYP/6-311G(d,p) level. To this end, the 32CA reactions of nine simplest three-atom-components (TACs) with 2-methylpropane were selected. The electronic structure of the reagents has been characterised through the Electron Localisation Function (ELF) and the Conceptual DFT. The energy profiles of the two regioisomeric reaction paths and ELF of the transition state structures are studied to understand the origin of the regioselectivity in these 32CA reactions. This MEDT study permits to conclude that the least electronegative ends X1 atom of these TACs controls the asynchronicity in the C-X (X = C,N,O) single bond formation, and consequently, the regioselectivity. This behaviour is a consequence of the fact that the creation of the non-bonding electron density required for the formation of the new CX single bonds has a lesser energetic cost at the least electronegative X1 atom than that at the Z3 one.

In the recent past about 40 botulinum neurotoxin (BoNT) subtypes belonging to serotypes A, B, E, and F pathogenic to humans were identified among hundreds of independent isolates. BoNTs are the etiological factors of botulism and represent potential bioweapons, but are also recognized pharmaceuticals for efficient counteraction of hyperactive nerve terminals in a variety of human diseases. The detailed biochemical characterization of subtypes as the basis for development of suitable countermeasures and possible novel therapeutic applications is lagging behind the increase in new subtypes. Here we report the primary structure of a ninth subtype of BoNT/F. Its amino acid sequence diverges by at least 8.4% at the holotoxin and 13.4% on the enzymatic domain level from all other known BoNT/F subtypes. We found that BoNT/F9 shares the scissile Q⁵⁸/K⁵⁹ bond in its substrate vesicle associated membrane protein 2 with the prototype BoNT/F1. Comparative biochemical analyses of four BoNT/F enzymatic domains showed that the catalytic efficiencies decrease in the order F1 > F7 > F9 > F6 and vary by up to factor eight. K_M values increase in the order F1 > F9 > F6 ≈ F7, whereas k_cat decreases in the order F7 > F1 > F9 > F6. Comparative substrate scanning mutagenesis studies revealed a unique pattern of crucial substrate residues for each subtype. Based upon structural coordinates of F1 bound to an inhibitor polypeptide the mutational analyses suggest different substrate interactions in the substrate binding channel of each subtype.

In order for the body to function properly, it needs not only food, but also nutrients and non-nutritive bioactive compounds that have an immunomodulating effect. This applies not only to healthy people, but especially to people with accompanying chronic diseases, including type 2 diabetes. Unfortunately, the current food industry and the use of highly processed food promote nutritional deficiencies. Many studies confirm their occurrence in patients with type 2 diabetes. The article presents the influence of selected nutrients on the functioning of the immune system, which ensures homeostasis of the body, with particular emphasis on type 2 diabetes. The role of macroelements, microelements, vitamins and selected substances, such as omega-3 acids, coenzyme Q10 and alpha-lipoic acid. The minimum scope of tests that should be performed in patients to directly or indirectly determine the degree of malnutrition in this group of patients is presented.

Arf-like protein 2 (ARL2) is a ubiquitously expressed small GTPase with multiple functions. In cell culture, ARL2 participates with tubulin cofactor D (TBCD) in the neogenesis of tubulin αβ-heterodimers, the building blocks of microtubules. To evaluate this function in retina, we conditionally deleted ARL2 in mouse retina at two distinct stages, either during embryonic development (retArl2-/-) or after ciliogenesis specifically in rods (rodArl2-/-). retArl2-/- retina sections displayed distorted nuclear layers and a disrupted microtubule cytoskeleton (MTC) as early as postnatal day 6 (P6). Rod and cone outer segments (OS) did not form. By contrast, rod ARL2 knockouts were stable at postnatal day 35 and revealed normal ERG responses. Cytoplasmic dynein is reduced in retArl2-/- inner segments (IS), suggesting that dynein may be unstable in the absence of a normal MTC. We investigated microtubular stability in the absence of either ARL2 (retARL2-/-) or DYNC1H1 (retDync1h1-/-), the dynein heavy chain, and found that both the retArl2-/- and retDync1h1-/- retinas exhibited reduced microtubules and nuclear layer distortion. The results suggest that ARL2 and dynein depend on each other to generate a functional MTC during early photoreceptor development.

Rapid development and deployment of vaccines greatly reduced mortality and morbidity during the COVID-19 pandemic. The most widely used COVID-19 vaccines approved by national regulatory authorities require intramuscular administration. SARS-CoV-2 initially infects the upper respiratory tract where the infection can be eliminated with little or no symptoms by an effective immune response. Failure to eliminate SARS-CoV-2 in the upper respiratory tract results in lower respiratory tract infections that can lead to severe disease and death. Presently used intramuscularly administered COVID-19 vaccines are effective in reducing severe disease and mortality but are not entirely able to prevent asymptomatic and mild infections as well as person to person transmission of the virus. Individual and population differences also influence susceptibility to infection and the propensity to develop severe disease. This article provides a perspective on the nature and the mode of delivery COVID-19 vaccines that can optimize protective immunity in the upper respiratory tract to reduce infections and virus transmission as well as severe disease.

The COVID-19 pandemic drew public attention back to the living conditions related to housing, access to green areas in close neighbourhood and nearby recreation. Several studies confirm that visiting green spaces improved the health and wellbeing in times of crisis. This representative study for the metropolitan area of Vienna, Austria’s capital, confirms the high relevance of contact with nature, particularly for citizens to cope with the negative consequences and perceived stress, anxiety, nervousness and many other negative symptoms experienced during the health crisis. It highlights the importance of nearby smaller but also medium to large scale green areas in cities for health and wellbeing of the population. Moreover, it specifically adds novel insights on age effects in use and perception of urban green spaces during COVID-19 pandemic. The online panel survey (n=1012) was conducted in summer 2021. In order to obtain a representative sample reflective of the population’s characteristics, a (stratified) random sample was selected by applying the quota method. The objective was to obtain a sample which represented gender, age and regional distribution of the population of the City of Vienna as well as the immediately surrounding local communities. Interestingly, particularly young people spent more time outside in green areas during the pandemic, discovered novel spaces for the first time and stated a high relevance of contact with nature for their wellbeing. Elderly people above sixty five, on the contrary, stayed more frequently at home. Significant differences are visible between the age groups also with regard to negative symptoms experienced in case of restricted access to green areas due to strict pandemic measures such as lockdowns and quarantine. All age groups, however, similarly acknowledged the importance of green areas for their physical, mental and emotional health in general during the pandemic.

Observing cultivated crops and other forms of land use is an important environmental and economic concern for agricultural land management and crop classification. Crop categorization offers significant crop management data, ensuring food security, and developing agricultural policies. Remote sensing data, especially publicly available Sentinel 1 and 2 data, has effectively been used in crop mapping and classification in cloudy places because of their high spatial and temporal resolution. This study aimed to improve crop type classification by combining Sentinel-1 (Synthetic Aperture Rader (SAR)) data and the Sentinel-2 Multispectral Instrument (MSI) data. In the study, Random Forest (RF) and Classification and Regression Trees (CART) classier were used to classify grain crops (Barley and Wheat). The classification results based on the combination of Sentinel-2 and Sentinel-1 data indicated an overall accuracy (OA) of 93 % and a kappa coefficient (K) of 0.896 for RF and (89.15%, 0.84) for the CART classifier. It is suggested to employ a mix of radar and optical data to attain the highest level of classification accuracy since doing so improves the likelihood that the details will be observed in comparison to the single-sensor classification technique and yields more accurate results.

DNA methylation is one of the epigenetic mechanisms which have been implicated in cellular differentiation, ageing and disease development. The effect of hypomethylating drug 5-aza-2´deoxycytidine (5-aza dC) on the biosynthetic profile of caudal region chondrocytes from chick sternum was studied in detail. The chondrocytes in culture were treated with varying doses of 5-aza dC for 48h and maintained subsequently without the treatment and harvested at selected time points for analysis of growth and differentiation status. 15µg/ml of 5-aza dC showed optimum Concentration at which there was a significant increase in DNA synthesis and RNA synthesis as per cell basis. There was also a significant increase in total protein synthesis and collagen synthesis as per cell basis at this concentration. This optimal concentration also showed to up regulate the gene expression of Type X collagen and alkaline phosphatase, which are the marker of hypertrophic chondrocyte expression. These results further support the notion that methylation is the major epigenetic factor controlling the differentiation and maturation of chondrocytes.

The objective of this study is to investigate how different therapies modulating insulin resistance, either causally or consequently, affect metabolic parameters in treatment-naive subjects with T2DM. A total of 212 subjects were assigned to receive either a tight Japanese diet (n=65), pioglitazone at doses ranging from 15-30 mg/day (n=70), or canagliflozin at doses ranging from 50-100 mg/day (n=77) for a duration of three months. Correlations and changes (Δ) in metabolic parameters relative to insulin resistance were investigated. Across these distinct therapeutic interventions, ΔHOMA-R exhibited significant correlations with ΔFBG and ΔHOMA-B, while demonstrating a negative correlation with baseline HOMA-R. However, other parameters such as ΔHbA1c, ΔBMI, ΔTC, ΔTG, Δnon-HDL-C, or ΔUA displayed varying patterns depending on the treatment regimens. Participants were stratified into two groups based on the median value of ΔHOMA-R: the lower half (X) and upper half (Y). Group X consistently demonstrated more pronounced reductions in FBG compared to Group Y across all treatments, while other parameters including HbA1c, HOMA-B, TC, TG, HDL-C, non-HDL-C, TG/HDL-C ratio, or UA exhibited distinct regulatory responses depending on the treatment administered These findings suggest that 1) regression to the mean is observed in the changes of insulin resistance across these therapies. 2) modulation of insulin resistance with these therapies, either causally or consequentially, results in differential effects on glycemic parameters, beta-cell function, specific lipids, body weight or UA.

In the Mediterranean area, vegetation dynamics and phenology analyzed over a long time can have an important role in highlighting changes in land use and cover as well as the effect of climate change. Over the last 30 years, remote sensing has played an essential role in bringing about these changes thanks to many types of observations and techniques. Satellite images are to be considered an important tool to grasp these dynamics and evaluate them in an inexpensive and multidisciplinary way thanks to Landsat and Sentinel satellite constellations. The integration of these tools holds a dual potential: on one hand, allowing to obtain longer historical series of reflectance data, while on the other hand, making data available with a higher frequency even within a specific timeframe. The study aims to conduct a comprehensive cross-comparison analysis of long-time series pixel values in the Mediterranean regions. For this scope comparisons between Landsat-7 (ETM+), Landsat-8 (OLI), and Sentinel-2 (MSI) satellite sensors were conducted based on surface reflectance products. We evaluated these differences using Ordinary Least Squares (OLS) and Major Axis linear regression (RMA) analysis on points extracted from over 15,000 images across the Mediterranean basin area from 2017 to 2020. Minor but consistent differences were noted, necessitating the formulation of suitable adjustment equations to better align Sentinel-2 reflectance values with those of Landsat-7 or Landsat-8. The results of the analysis are compared with the most used harmonization coefficients proposed in the literature, revealing significant differences. The root mean square deviation, the mean difference and the orthogonal distance regression (ODR) slope show an improvement of the parameters for both models used (OLS and RMA) in this study. The discrepancies in reflectance values lead to corresponding variations in the estimation of biophysical parameters, such as NDVI, showing an increase in the ODR slope of 0.3. Despite differences in spatial, spectral, and temporal characteristics, we demonstrate that integration of these datasets is feasible through the application of band-wise regression corrections for a sensitive and heterogeneous area like those of the Mediterranean basin area.

The worldwide prevalence of type 2 diabetes (T2D) and prediabetes is rapidly increasing, particularly in children, adolescents, and young adults. Oxidative stress (OxS) has emerged as a likely initiating factor in T2D. The role of natural antioxidant products in combating T2D is best evaluated in the context of the complex physiological processes that modulate T2D-OxS such as glycemic control and exercise. The role of natural antioxidant compounds such as vitamin E in T2D must likewise be considered beyond their roles as inhibitors of OxS. In addition to antioxidant properties, vitamin E vitamers (tocopherols and tocotrienols) also exhibit distinct abilities to regulate cellular signal transduction pathways important to T2D progression. Most research on the role of vitamin E in T2D or prediabetes has been limited to tocopherols (Ts) but emerging trials with tocotrienols (T3s) show promise. Minimizing factors that induce chronic damaging OxS and maximizing natural antioxidant protective factors may provide a means of preventing or slowing T2D progression. This “optimal redox” (OptRedox) approach also provides a framework in which to discuss the potential benefits of natural antioxidant factors such as antioxidant products. Since early, effective intervention is critical, the OptRedox strategy would be optimally effective if implemented in the pediatric population.

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

Type 2 diabetes mellitus(T2DM) is an increasingly prevalent and serious health problem. Its onset is typically associated with metabolic disorders and disturbances in the gut microbiota. Previous studies have reported the anti-T2DM effects of Pueraria thomsonii Radix as a functional food. However, the mechanism of action is still unknown. In this study, the effects of Pueraria thomsonii Radix water extract(PTR) on db/db mice were evaluated by pharmacology, metabolomics, and 16S rRNA gene sequencing. The results showed that PTR could improve the body weight of mice, reduce fasting blood glucose(FBG), urinary glucose(UGLU), homeostasis model assessment insulin resistance(HOMA-IR), urinary albumin/creatinine ratio(UACR), and reduce pancreatic tissue damage. Metabolomics showed that the Model group produced 109 differential metabolites, of which 74 could be regulated by PTR. 16S rRNA sequencing was done in fecal samples and results showed that PTR could reduce the Firmicutes/Bacteroidetes ratio(F/B) associated with obesity and regulate 3 beneficial bacteria and 1 harmful bacteria. In conclusion, the results showed that PTR could ameliorate T2DM symptoms, metabolic disorder, and gut microbiota imbalance of db/db mice, and it was superior to metformin in some aspects. We suggested for the first time that γ-aminobutyric(GABA) may be involved in the regulation of the microbiota-gut-brain axis(MGB) and thus affect the metabolic disorders associated with T2DM. This study will provide a scientific basis for the development of functional food with PTR.

Background: Nutrient supplements are widely used for type 2 diabetes (T2D) yet evidence-based guidance for clinicians is lacking. Methods: We searched the four electronic databases from November 2015–December 2021. The most recent, most comprehensive, high-ranked systematic reviews, meta-analyses and/or umbrella reviews of randomised controlled trials in adults with T2D were included. Data were extracted on study characteristics, aggregate outcome measures per group (glycemic control, measures of insulin sensitivity and secretion), adverse events, and GRADE assessments. Quality was assessed using AMSTAR-2. Results: Twelve meta-analyses and one umbrella review were included. There was very low certainty evidence that chromium, Vitamin C and omega-3 polyunsaturated fatty acids (-3 PUFAs) were superior to placebo for the primary outcome of HbA1c (MD -0.54%, -0.54% and ES -0.27 respectively). Probiotics were superior to placebo for HbA1c (WMD -0.43%). There was very low certainty evidence that Vitamin D was superior to placebo for lowering HbA1c in trials of <6 months (MD -0.17%). Magnesium, zinc, Vitamin C, probiotics and polyphenols were superior to placebo for FBG. Vitamin D was superior to placebo for insulin resistance. Data on safety was limited. Conclusions: Future research should identify who may benefit from nutrient supplementation, safety, and optimal regimens and formulations.

In dentistry, maxillofacial surgery, traumatology, and orthopedics, there is a need to use osteoplastic materials that have not only osteoinductive and osteoconductive properties but are also convenient for use. In the study, compositions based on collagen hydrogel were developed. Polylactide granules (PLA) or a traditional bone graft, a mixture of hydroxyapatite and β-tricalcium phosphate (HAP/β-TCP), were used for gel filling to improve mechanical osteoconductive properties of compositions. The mechanical tests showed that collagen hydrogels filled with 12 wt% highly porous PLA granules (elastic modulus 373 ± 55 kPa) or 35 wt% HAP/β-TCP granules (elastic modulus 451 ± 32 kPa) had optimal manipulative properties. All composite components were cytocompatible. The cell’s viability was above 90%, and the components’ structure facilitated the cell’s surface adhesion. The bone morphogenetic protein-2 (BMP-2) provided osteoinductive composition properties. It was impregnated directly into the collagen hydrogel with the addition of fibronectin or inside porous PLA granules. The implantation of a collagen hydrogel with BMP-2 and PLA granules into a critical-size calvarial defect in rats led to the formation of the most significant volume of bone tissue: 61 ± 15%. It was almost 2.5 times more than in the groups where a collagen-fibronectin hydrogel with a mixture of HAP/β-TCP (25 ± 7%) or a fibronectin-free composition with porous PLA granules impregnated with BMP-2 (23 ± 8%) were used. Subcutaneous implantation of the compositions also showed their high biocompatibility and osteogenic potential in the absence of a bone environment. Thus, the collagen-fibronectin hydrogel with BMP-2 and PLA granules has optimal biocompatibility, osteogenic, and manipulative properties.

Obesity causes insulin resistance (IR) through systemic low-grade inflammation and can lead to type 2 diabetes mellitus (T2DM). However, the mechanisms that cause IR and T2DM in non-obese individuals are unclear. The Goto-Kakizaki (GK) rat develops IR spontaneously and is a model of non-obese T2DM. These rats exhibit hyperglycemia beginning at weaning and exhibit lower body mass than control Wistar rats. Herein, we tested the hypothesis that macrophages of GK rats are permanently in a pro-inflammatory state, which may be associated with a systemic inflammation condition that mimics the pathogenesis of obesity-induced T2DM. Using eighteen-week-old GK and control Wistar rats, we investigated the proportions of M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages isolated from the peritoneal cavity. Additionally, the production of inflammatory cytokine and reactive oxygen species (ROS) in cultured macrophages under basal and stimulated conditions was assessed. It was found that phorbol myristate acetate (PMA) stimulation increased GK rat macrophage ROS production by 90-fold compared to basal levels. This response was also three times more pronounced than in control cells (36-fold). The production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), tended to be upregulated in cultured macrophages from GK rats under basal conditions. Macrophages from GK rats produced 1.6 times more granulocyte-macrophage colony-stimulating factor (GM-CSF), 1.5 times more monocyte chemoattractant protein-1 (MCP-1) and 3.3 times more TNF-α than control cells when stimulated with lipopolysaccharide (LPS) (p = 0.0033; p = 0.049; p = 0.002, respectively). Moreover, compared to control cells, GK rats had 60% more M1 (p = 0.0008) and 23% less M2 (p = 0.038) macrophages. This study is the first to report macrophage inflammatory reprogramming towards a pro-inflammatory state in GK rats.

This paper focuses on evaluating airline service quality from the perspective of passengers view. Until now a lot of researches has performed in airline service quality evaluation in the world but a little research has been conducted in Iran, yet. In this research a framework for measuring airline service quality in Iran is proposed. After reviewing airline service quality criteria, SSQAI model was selected because of its comprehensiveness in covering airline service quality dimensions. SSQAI questionnaire items were redesigned to adopt with Iranian airlines requirements and environmental circumstances in the Iran's economic and cultural context. This study includes fuzzy decision-making theory, considering the possible fuzzy subjective judgment of the evaluators during airline service quality evaluation. Fuzzy TOPSIS have been applied for ranking airlines service quality performances. Three major Iranian airlines which have the most passenger transfer volumes in domestic and foreign flights, were chosen for evaluation in this research. Results demonstrated Mahan airline has got the best service quality performance rank in gaining passengers' satisfaction with delivery of high quality services to its passengers, among the three major Iranian airlines. IranAir and Aseman airlines placed in the second and third rank, respectively, according to passenger's evaluation.Statistical analysis have been used in analyzing passenger responses. Due to abnormality of data, Non-parametric tests were applied. To demonstrate airline ranks in every criterion separately, Friedman test was performed. Variance analysis and Tukey test were applied to study the influence of increasing in age and educational level of passengers' on degree of their satisfaction from airline's service quality. Results showed that age has not significant relation with passenger satisfaction of airlines, however increasing in educational level demonstrated a negative impact on passengers' satisfaction from airline's service quality.

In this study, we aimed to reveal the proinflammatory effects of serum 25-hydroxyvitamin D3 (Vit D) deficiency and insufficiency in new-onset type 2 diabetes mellitus (T2DM) and prediabe-tes. We recruited 84 prediabetes patients, 94 new-onset T2DM patients and 113 healthy partici-pants. Levels of C-reactive protein (CRP), fibrinogen, ferritin, interleukin-1β (IL-1β), interleu-kin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) were measured in the serum of the par-ticipants. The ANOVA Bonferonni and Kruskal Wallis Dunn tests were used for the comparison of the inflammation markers and vitamin D levels between the groups. Upon covariance analy-sis with age, gender and BMI; Vit D levels of T2DM group were found to be significantly lower (p<0.003). Proinflammatory markers and CRP were found to be significantly higher in predia-betic and diabetic subjects. In the prediabetes group, IL-1β, IL-6, IL-8, TNF-α and MAPK were significantly higher in those with Vit D insufficiency and deficiency groups. In T2DM group, IL-1β, IL-6, IL-8, TNF-α, NF-κB, MAPK and CRP were significantly higher in those with Vit D insufficiency and deficiency. Our study emphasizes the proinflammatory effects of Vit D on the initiation of inflammation in both prediabetes and diabetes mellitus.

Forest damage has become more frequent in Europe in the last decades, and remote sensing offers a powerful tool for monitoring them rapidly and cost-effectively. A novel approach was developed to utilize high-resolution ESA Sentinel-2 satellite imagery and Google Earth Engine cloud computing. The processing, analysing, and visualization of vegetation and water index (NDVI, NDVIch, Z NDVI, EVI, NDWI) maps and charts derived from satellite images took place in the cloud to ensure the detection of forest disturbances in the Hungarian study site for the period 2017-2020. The index maps were classified to reveal forest disturbances, and the cloud-based method successfully showed drought and frost damage in the oak-dominated Nagyerdő forest of Debrecen. Differences in the reaction to damage between tree species were visible in the index values, therefore a Random Forest Machine Learning classifier was applied to show the spatial distribution of dominant species. Accuracy assessment was accomplished with confusion matrices that compared classified index maps to field-surveyed data, demonstrating 71% Total Accuracy for forest damage and 76% for tree species. Based on the results of this study and the resilience of Google Earth Engine, the presented method has the potential to be extended to monitor the entire Hungary.

NASA’s ICESat-2space-borne photon-counting lidar mission is providing global elevation measurements that will provide significant benefits to a variety of bio-geoscience research applications. Given the novelty of elevation and the derived data products from the ICESat-2 mission, the research community needs software tools that can facilitate photon-level analyses to support product validation and development new analysis methods. Here, we describe PhotonLabeler, a free graphic user interface (GUI) for manual labeling and visualization of ICESat-2 Geolocated Photon data (ATL03). Developed in MATLAB, the GUI facilitates the reading and display of ATL03 Hierarchical Data Format (HDF) files, the manual labeling of individual photons into target classes of choice using a number of point selections tools and enables eventual saving of labeled data in ASCII format. Other capabilities include saving and loading of labeling sessions to manage labeling tasks over time. We expect labeled data generated using the application to serve two main purposes. First, serve as ground truth for validating various products from ICESat-2 mission, especially for study sites around the world that do not have existing reference datasets such as airborne lidar. Second, serve as training and validation data in the development of new algorithms for generating various ICESat-2 data products. We demonstrate the first use case through a validation case study for the land and vegetation product (ATL08), which provides canopy and terrain height estimates, over two sites. For the first site, located in northwestern Zambia, we used ICESat-2 ATL03 data acquired at night and for our second site in Texas, US, we used ATL03 data acquired during the day. The PhotonLabeler application is freely available as a compiled MATLAB binary to enable free access and utilization by interested researchers.

Rapid Visual Screening (RVS) is a procedure that estimates structural scores for buildings and prioritize their retrofit and upgrade requirements. Despite the speed and simplicity of RVS, many of the collected parameters are non-commensurable and include subjectivity due to visual observations. It might cause uncertainties in the evaluation, which emphasizes the use of a fuzzy-based method. This study aims to propose a novel RVS methodology based on the interval type-2 fuzzy logic system (IT2FLS) to set the priority of vulnerable building to undergo detailed assessment while covering uncertainties and minimizing their effects during evaluation. The proposed method estimates the vulnerability of a building, in terms of Visual Damage Index, considering the number of stories, age of building, plan irregularity, vertical irregularity, building quality, and peak ground velocity, as inputs with a single output variable. Applicability of the proposed method has been investigated using a post-earthquake damage database of 28 reinforced concrete buildings from the Bingöl earthquake in Turkey.

Glacier dynamics play an important role in the mass balance of many glaciers, ice caps and ice sheets. In this study we exploit Radarsat-2 (RS-2) Wide Fine (WF) data to determine the surface speed of Svalbard glaciers in the winters of 2012/2013 and 2013/2014 using Synthetic Aperture RADAR (SAR) offset and speckle tracking. The RS-2 WF mode combines the advantages of the large spatial coverage of the Wide mode (150 x 150 km) and the high pixel resolution (9m) of the Fine mode and thus has a major potential for glacier velocity monitoring from space through offset and speckle tracking. Faster flowing glaciers (1.95 m d^-1 - 2.55 m d^-1) which are studied in detail are Nathorstbreen, Kronebreen, Kongsbreen and Monacobreen. Using our Radarsat-2 WF dataset, we compare the performance of two SAR tracking algorithms, namely the GAMMA Remote Sensing Software and a custom written MATLAB script (GRAY method) that has primarily been used in the Canadian Arctic. Both algorithms provide comparable results, especially for the faster flowing glaciers and the termini of slower tidewater glaciers. A comparison of the WF data to RS-2 Ultrafine and Wide mode data reveals the superiority of RS-2 WF data over the Wide mode data.

Multispectral and 3D LiDAR remote sensing data sources are valuable tools for characterizing the 3D vegetation structure and thus understanding the relationship between forest structure, biodiversity and microclimate. This study focuses on mapping riparian forest species in the canopy strata using a fusion of Airborne LiDAR data and multispectral multi-sources and multi-resolution satellite imagery; Sentinel-2 and Pleiades at tree level. The idea is to assess the contribution of each data source in the tree species classification at the considered level. The data fusion was processed at feature-level and decision level. At feature level, LiDAR 2D attributes were derived and combined with vegetation indices. At decision level, LiDAR data was used for 3D tree crown delimitation providing unique trees or groups of trees that are used as a support for the species classification. Data augmentation techniques were used to improve the training process. Best results were obtained by the fusion of Sentinel-2 time series and LiDAR data with a Kappa of 0.66 thanks to red-edge based indices that better discriminate vegetation species and the temporal resolution of Sentinel-2 images that allows monitoring the phenological stages helping to discriminate the species.

A novel synthetic strategy is disclosed to prepare a new class of metalorganic copolymers which contain iron(II) clathrochelate building blocks by employing a mild and cost-effective copper-catalyzed [4 + 2] cyclobenzannulation reaction, using three specially designed diethynyl iron(II) clathrochelate synthons. The target copolymers CBP1-3 were isolated in high purity and excellent yields as proven by their structural and photophysical characterization, namely, Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS) and UV-vis absorption and emission spectroscopies. Thermogravimetric analysis (TGA) of CBP1-3 reveals excellent chemical stability. Investigation of the adsorption properties of the target copolymers towards the carcinogenic methyl red dye from aqueous solution reveals a quantitative uptake in 30 minutes. Isothermal adsorption studies disclose that methyl red uptake from aqueous solution follows Langmuir model for all the target copolymers reaching a maximum adsorption capacity (qm) of 431 mg g‒1, whereas kinetic investigation reveals that the adsorption follows pseudo first-order with an equilibrium adsorption capacity (qe,cal) of 79.35 mg g‒1 and whose sorption property was sustained even after its reuse several times.

Short stature has been associated with increased various disease and all-cause death, but no reliable data exist the association between height and end-stage renal disease (ESRD) in diabetic patients. We investigated the relationship between short stature, development of ESRD, and mortality in type 2 diabetes. This study analyzed clinical data using the National Health Insurance Database in Korea. Height was stratified by five groups according to age and sex. Risk of ESRD and all-cause mortality was analyzed with Cox proportional hazards models. During a 6.9-year follow-up period, 220,457 subjects (8.4%) died and 28,704 subjects (1.1%) started dialysis. Short stature significantly increased the incidence of ESRD and all-cause mortality in the overall cohort analysis. In multivariable analysis, hazard ratios (HR) for development of ESRD comparing the highest versus lowest quartiles of adult height were 0.86 (95% confidence interval (CI), 0.83–0.89). All-cause mortality also decreased with highest height compared to patients with lowest height after fully adjusting for confounding variables (HR 0.79, 95% CI, 0.78–0.81). Adult height had an inverse relationship with newly diagnosed ESRD and all-cause in both males and females. Short stature is strongly associated with an increased risk of ESRD and all-cause mortality in type 2 diabetes.

3,4-Dihydroquinolin-2(1H)-ones represent a class of valuable bioactive compounds with six-membered nitrogen-containing heterocyclic structures. The development of simple, mild and efficient synthetic methods has been widely concerned by synthetic chemists. In this review, we have summarized a series of different synthetic strategies for the synthesis of dihydroquinoline-2(1H)-ones via catalytic annulation of α,β-unsaturated N-arylamides in the past decade, including covering electrophilic cyclization, radical initiated cyclization and photochemical cyclization reactions. Besides, the substrate scope and mechanistic details are also discussed. This paper will provide a useful reference for the development of diverse synthesis methodologies of 3,4-dihydroquinolin-2(1H)-ones.

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.

The effects of morphine (MOR) and dexmedetomidine (DEX) on the MAC of isoflurane were measured in rats chronically treated with the synthetic cannabinoid WIN 55,212-2 (WIN55). Methods: The MAC of isoflurane was determined in 32 male rats from expiratory samples at the time of tail clamping. The effects of morphine (MAC(ISO+MOR)) and dexmedetomidine (MAC(ISO+DEX)) on the MAC of isoflurane in untreated rats and rats treated for 21 days with WIN 55,212-2 (MAC(ISO+WIN55+MOR)) and (MAC(ISO+WIN55+DEX)) were measured. Prior to the administration of morphine and dexmedetomidine, the MAC of the isoflurane was measured in both untreated rats (MAC(ISO)) and those treated with WIN 55,212-2 (MAC(ISO+WIN55)). Results: The minimum alveolar concentration was measured as 1.32 ± 0.06 in the MAC(ISO) group and 1.69 ± 0.09 in the MAC(ISO+WIN55) group. The MAC of the MAC(ISO+MOR) group was 0.97 ± 0.02 (26% less than the control group, MAC(ISO)). MAC was measured as 1.55 ± 0.08 in the MAC(ISO+WIN55+MOR) group (8% less than the MAC(ISO+WIN55) group), 0.68 ± 0.10 in the MAC(ISO+DEX) group (48% less than the control group, MAC(ISO)), and 0.67 ± 0.08 in the MAC(ISO+WIN55+DEX) group (60% less than the MAC(ISO+WIN55) group). Conclusions: The administration of WIN 55,212-2 for 21 days increases the MAC of isoflurane in rats. The sparing effect on isoflurane of morphine decreases in rats chronically treated with the synthetic cannabinoid, WIN 55,212-2. Dexmedetomidine increases its sparing effect on the minimum alveolar concentration of isoflurane in rats chronically treated with WIN 55,212-2.

Background: The course of obesity and type 2 diabetes (T2D) development is highly dependent on adipose tissue (AT) angiogenesis. Moreover, angiogenic microRNAs (miRNAs) play pivotal role in AT functionality. The aim of this study was to analyze the relationship of the human AT miR-221-3p/222-3p cluster and their regulatory network with obesity and T2D. Methods: miR-221-3p/222-3p and their target genes (TG) expression levels were measured in visceral and subcutaneous ATs from patients classified according to their BMI and to their glycemic status with a high degree of insulin resistance (IR) and T2D. In silico analyses of miR-221-3p/222-3p and their TGs were performed to identify relevant signaling pathways. Results: A multivariate analysis, including the simultaneous expression of miR-221-3p and miR-222-3p as dependent variables, showed significant differences considering the variables; tissue depot, obesity, IR and T2D altogether as independent variables. In addition, miRNAs and their TGs were differentially expressed according to obesity degree, glycemic status, and AT depot type. Our in silico analysis showed that miR-221-3p/222-3p cluster TGs are mostly involved in angiogenesis, WNT signaling pathway and apoptosis. Conclusion: These findings suggest that the miR-221-3p/222-3p cluster and their related regulatory networks could represent tangible targets for the management of obesity and associated metabolic disorders

Satellite Crop Detection technologies are focused on detection of different types of crops on the field in the early stage before harvesting. Crop detection is usually done on a time series of satellite data by classification of the desired fields. Currently, data obtained from Remote Sensing (RS) are used to solve tasks related to the identification of the type of agricultural crops, also modern technologies using AI methods are desired in the postprocessing part. In this challenge Sentinel-1 and Sentinel-2 time series data were used due to their periodic availability. Our focus was to develop methodology for classification of time series of Sentinel 2 and Sentinel 1 data and compare how accuracy of classification can be increased, but also how to guarantee availability of data. We analyse phenology of single crops and on the basis of this analysis we started to provide crop classification. Original crop classifications were made from Enhanced Vegetation Index (EVI) layers made from Sentinel-2 time-series data and then we added also . To increase accuracy we also integrate into the process parcel borders and provide classification of fields..

As humans age, aberrancies in several signaling pathways occur. In the aging population, some patients display abnormal bone morphogenetic protein (BMP) signaling. This can lead to osteoporosis (OP), a debilitating bone disorder caused by an imbalance between osteoblasts and osteoclasts. In 2002, the Food and Drug Administration (FDA) approved usage of recombinant human BMP-2 (rhBMP-2) during spinal fusion surgery as it is crucial for bone formation. However, complications have been reported with rhBMP-2 and primary osteoblasts isolated from OP patients are unresponsive to BMP-2. While patient samples are available, previous medical history may alter results. Therefore, C57BL/6 mice, an aging model that displays aberrant BMP-signaling, can be utilized to investigate OP and aging. We show that BMP receptor type Ia (BMPRIa) is upregulated in the bone marrow stromal cells (BMSCs) of 15-month mice similar to previous data. We show that a conjugation between BMP-2 and Quantum Dots (QDot®s) effectively binds to BMPRIa and can investigate BMP-2 activity. After incubating BMSCs with methyl-β-cyclodextrin (MβCD), BMP-signaling is restored in 15-month mice as shown by western blotting and the von Kossa assay. MβCD may be used to rescue BMPRIa and the BMP-signaling pathway can be utilized by future therapeutics to treat OP.

Water reuse for irrigation is increasingly recognized as an essential and economical strategy in areas with water scarcity. A simple, low-cost, low-maintenance, and highly efficient Pond-In-Pond (PIP) treatment system can be used for wastewater reuse. PIP is a treatment technology in which two types of ponds -- anaerobic and aerobic -- are combined into a single pond and consist of a deeper inner section entirely submerged within the outer pond. Previous studies on PIPs and PIP-like systems have reinforced the potential for reuse through promising performance results with BOD removal over 80% and a reduction in land area requirements by approximately 40%. Yet, no prior efforts have been made to understand the performance mechanism of such systems. This study makes use of two, 2-D modeling tools in developing a fundamental understanding of PIP flow dynamics and the expected performance. The modeling results showed that the PIP configuration offers improved flow diversion along with reduced flow velocity. Additionally, the PIP retained approximately 17% more (p<0.05) particles than the traditional pond with most of the particles concentrated within the inner pond. Lower velocity and the higher solids retention in the PIP thus allowed for better treatment performance compared to traditional ponds. The findings from this study can be used as preliminary data for future in-depth investigations of the PIP system leading toward effective and optimal designs. This will help address the major societal concern of water scarcity with low-cost and effective wastewater treatment.

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 new compound containing a triene, a tetrahydropyran ring and glycine ester functionalities, restricticin B (1), together with four known compounds (2-5) were obtained from the EtOAc extract of the marine fungus Penicillium janthinellum. The planar structure of 1 was determined by detailed analyses of MS, 1D and 2D NMR data. The relative and absolute configurations of 1 were established via analyses of NOESY spectroscopy data, comparison of optical rotation values with those of restricticin derivatives reported and electronic circular dichroism (ECD). All the compounds were screened for their anti-neuroinflammatory effects in lipopolysaccharide (LPS)-induced BV-2 microglia cells. Restricticin B (1) and N-acetyl restricticin (2) exhibited anti-neuroinflammatory effects by suppressing the production of pro-inflammatory mediators in activated microglial cells.

This study continued the analysis of immunization with the receptor binding domain (RBD) associated with the adjuvants Dimethyldioctadecylammonium bromide (DDA) and Saponin (Sap) (RBD+DDA/Sap) or Aluminum hydroxide (AH) and outer membrane vesicles (OMVs) of Neisseria meningitidis (RBD+AH/OMV); from adult to old age and assessed maternal-fetal transference of antibodies. Outbred Swiss mice were immunized with 2 intramuscular (IM) doses with the antigenic preparations RBD+DDA/Sap, RBD+AH/OMV or RBD alone. The humoral immune response was evaluated using ELISA, avidity-ELISA, Immunoblotting and a Omicron-surrogate-neutralization assay (BA.1), while the cellular immune response was analyzed by ELISpot. Our previous work studied the IgG response; here, we verified that IgM levels were higher right after the immunization doses, but, as IgG, it persisted until 368 days after the immunization. The avidity of IgM increased from low to intermediate-to-high after the booster dose. RBD+DDA/Sap presented neutralizing indexes against Omicron at days 47 and 176, while RBD+AH/OMV showed neutralization on days 21, 47 and 176. Cellular response, measured 465 days after immunization, revealed IFN-Y and IL-4 secretion. The offspring of RBD+DDA/Sap had detectable antibodies, which decreased around 45 days after birth, the last point we analyzed. The results suggested that DDA/Sap is a promising adjuvant mixture to enhance humoral and cellular immune response against SARS-CoV-2, improving maternal-fetal transference of antibodies; cross-reactivity with Omicron variant; and the maintenance of antibodies for a long period.

Abstract: An efficient and environmentally Pumice as a new catalyst for designing of 3,4- dihydropyrimidin-2(1H) ones / thiones via one-pot multi component condensation of aromatic aldehydes, urea/ thiourea and ethyl acetoacetate or acetyl acetone in excellent yields (96-99 %). The advantages using of this new catalyst is very cheap, available, non-toxic, stable under thermal conditions, easy work-up, improved yields, the product of reaction is very pure without using chromatographic methods and solvent free conditions.

The main functions of the automated systems rely on the advanced sensors for detection and perception of the environment around the vehicle. Radars and cameras are commonly utilized to detect the potential obstacles and vehicles ahead on the road. Nevertheless, cameras can generate spurious detections in the extreme weather conditions such as fog, rain, dust, snow, dark, and heavy sunlight in the sky. Due to limitations in vertical field view of the radars, single radars are not reliable to detect the height of the targets precisely. In this paper, a triple radar arrangement (long-range, medium-range, and short-range radars) based on sensor fusion technique is proposed to detect objects with different size in level 2 Advanced Driver-Assistance (ADAS) system. The typical objects including truck, pedestrians, and animals are detected in different scenarios. The developed model considered ISO 26262 and ISO/PAS 21448 to reasonably address insufficient robustness and inability of the sensors. The models of sensor and level 2 ADAS systems are developed using MATLAB toolbox and Simulink. Sensor detection performance is determined by running simulations with triple radar setup. Obtained results demonstrate that the proposed approach generates accurate detections of targets in all tested scenarios.

How hematopoietic stem and progenitor cell (HSPC) fate decisions are affected by genetic alterations acquired during AML leukemogenesis is poorly understood and mainly explored in animal models. Here, we studied isocitrate dehydrogenases (IDH) genes mutations in the human model of HSPC and provide a review of the literature on this topic. IDH1/2 mutations occur in ~20% of AML, are recognized among the mutations earliest acquired during leukemogenesis, and are target of specific inhibitors (ivosidenib and enasidenib, respectively). In order to investigate the direct effects of these mutations on the HSPC we expressed by lentiviral transduction either IDH1-R132H or IDH2-R140Q mutants into human CD34+ healthy donor cells and analyzed the colony-forming unit (CFU) ability. CFU ability was dramatically compromised with a complete trilineage block of differentiation. Strikingly, the block was reversed by the specific inhibitors, confirming it was a specific effect induced by the mutants. In line with this observation, the CD34+ leukemic precursors isolated from a patient with IDH2-mutated AML at baseline and during enasidenib treatment showed over time a progressive and marked improvement of their fitness in terms of CFU ability and propensity to differentiate, attaining clonal trilinear reconstitution of hematopoiesis and complete hematological remission.

A timely inventory of agricultural areas and crop types is an essential requirement for ensuring global food security. Satellite remote sensing has proven to be an increasingly more reliable tool to identify crop types. With the Copernicus program and its Sentinel satellites, a growing source of satellite remote sensing data is publicly available at no charge. Here we use joint Sentinel-1 radar and Sentinel-2 optical imagery to create a crop map for Belgium. To ensure homogenous radar and optical input across the country, Sentinel-1 12-day backscatter composites were created after incidence angle normalization, and Sentinel-2 NDVI images were smoothed to yield dekadal cloud-free composites. An optimized random forest classifier predicted the 8 crop types with a maximum accuracy of 82% and a kappa coefficient of 0.77. We found that a combination of radar and optical imagery always outperformed a classification based on single-sensor inputs, and that classification performance increased throughout the season until July, when differences between crop types are largest. Furthermore we showed that the concept of classification confidence derived from the random forest classifier provided insight in the reliability of the predicted class for each pixel, clearly showing that parcel borders have a lower classification confidence. We concluded that the synergistic use of radar and optical data for crop classification led to richer information increasing classification accuracies compared to optical-only classification. Further work should focus on object-level classification and crop monitoring to exploit the rich potential of combined radar and optical observations.

We explored the outcomes of germline BRCA1/2 pathogenic/likely pathogenic variants (PVs/LPVs) in the endocrine-sensitive disease treated with first line standard of care cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Three studies retrospectively showed a reduction in overall survival (OS) and progression free survival (PFS) in gBRCA1/2m patients compared to both germinal BRCA1/2 wild type (gBRCA1/2wt) and to the untested population. Regarding the efficacy of PI3K inhibitors, there are no subgroup or biomarker analyses in which germinal BRCA status was explored. However, the biological interactions between the PIK3CA/AKT/mTOR pathway and BRCA1/2 at a molecular level could help us to understand the activity of these drugs when used to treat BC in BRCA1/2 PVs/LPVs carriers. The efficacy of trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate (ADC) targeting HER2 for HER2-low and HER2-positive (HER2+) BC, has been increasingly described. Unfortunately, data on T-DXd in HER2+ or HER2-low metastatic BC harboring germinal BRCA1/2 PVs/LPVs is lacking. Including germinal BRCA1/2 status in the subgroup analysis of the registration trials of this ADC would be of great interest, especially in the phase III trial DESTINY-breast04. This trial enrolled patients with HER2-negative (HER2-) and both HR+ and HR- metastatic disease, which can now be categorized as HER2-low. The HER2-low subgroup includes tumors that were previously classified as triple negative, so it is highly likely that some women were germline BRCA1/2 PVs/LPVs carriers and this data was not reported. Germline BRCA1/2 status will be available for a higher number of individuals with BC in the near future and data on the prognostic and predictive role of these PVs/LPVs is needed in order to choose the best treatment options.

A B S T R A C T Genital herpes disease is caused mainly by herpes simplex virus type 2 (HSV-2), which is sexually transmitted with a high prevalence in both developed and developing countries. No vaccine is currently available against genital herpes. In this study, we introduced and expressed two genes encoding HSV-2 glycoprotein D (gD) and VP16 protein and a GFP marker gene (control) in tobacco seedlings. Positive plant infection was assessed through characteristic tobacco mosaic virus disease symptoms on leaves and by monitoring the fluorescence emitted by the expressed GFP protein. Expression of the HSV-gD2 and VP16 antigens was verified by RT-PCR, ELISA and Western blot. As a proof of concept, the immunogenicity and the protection ability of the plant produced gD antigen was tested in a mouse model of genital herpes and compared to gD antigen produced in a mammalian expression system. This showed that the plant-gD preparation, when used in combination with a CpG oligodeoxynucleotide as adjuvant, was highly immunogenic and capable of inducing complete immunity to lethal vaginal HSV-2 challenge in mice. Thus, the data presented here may have implications for the development of a production system for highly immunogenic plant-based HSV-2 vaccine antigens.

Surface soil moisture (SSM) is a significant factor affecting crop growth. This paper presents a method for retrieving SSM over wheat-covered areas using synergy dual-polarization C-band Sentinel-1 synthetic aperture radar and Sentinel-2 optical data. Firstly, a modified water cloud model (WCM) was proposed to remove the influence of vegetation from the backscattering coefficient of the radar data. The vegetation fraction was then introduced in this WCM, and the vegetation water content (VWC) was calculated using multiple linear regression model. Subsequently, the support vector regression technique was used to retrieve the SSM. This approach was validated using in-situ measurements of the wheat field in Hebi, in the north of Henan Province. The key findings of this study are as follows: (1) Based on vegetation indices obtained from Sentinel-2; the proposed VWC estimation model can effectively eliminate the influence of vegetation; (2) compared with vertical transmit and horizontal receive polarization, vertical transmit and vertical receive polarization is better for detecting changes in SSM at different growth stages of wheat; and, (3) the validation results indicated that the proposed approach, based on Sentinel-1 and Sentinel-2 data, successfully retrieved SSM in the study area.

Abstract: Abnormal growth of oligodendrocyte precursor cells (OPCs) importantly contributes to the progression of glioblastoma tumors. Hence, molecules that block OPC growth may be of therapeutic importance in treating gliomas. 2-methoxyestradiol (2ME), an endogenous tubulin interacting metabolite of estradiol is effective against multiple proliferative disorders. Based on its anti-carcinogenic and anti-angiogenic actions it is undergoing phase II clinical trials. We hy-pothesize that 2ME may prevent glioma growth by targeting OPC growth. Here we tested this hypothesis by assessing the impact of 2ME on growth of OPC cell line “Oli-neu” and dissected the underlying mechanism(s). Treatment with 2ME inhibited OPC growth in a concentra-tion-dependent manner and accompanied with significant upregulation in expression of p21 and p27, negative cell cycle regulators. Moreover, treatment with 2ME altered OPC morphology from multi-arm processes to rounded cells. At concentrations of 1uM and greater 2ME induced apoptosis with increased expression of caspase 3, PARP and caspase-7 fragments, externalized phosphatidylserine staining / apopercentage and increased mitochondrial activity. Flow-cytometry and microscopic analysis demonstrated that 2ME triggers endoreduplication in a concentration-dependent fashion. Importantly, 2ME induced cyclin E, JNK1/2 and p53 expres-sion as well as OPC cell fusion, key mechanisms driving endoreduplication or whole-genome duplication. Importantly, inhibition of p53 with pfithrin-α rescued 2ME-induced endoreduplica-tion. The pro-apoptotic and endoreduplication actions of 2ME were accompanied with upregula-tion of survivin, cyclin A, Cyclin B, Cyclin D2, ppRB. Taken together our findings provide evi-dence that 2ME not only inhibits OPC growth and triggers apoptosis, but also activates OPCs in a survival - fight or flight mode leading to endoreduplication. This inherent survival character-istic of OPCs may, in part be responsible for drug resistance in gliomas as observed for many tubulin interacting drugs. Importantly, the fate of OPCs after 2ME treatment may depend on cell-cycle status of the individual cells. Combining tubulin-interfering molecules with drugs, such as pfithrin-α, that inhibit endoreduplication may help inhibit OPC/glioma growth and lim-it drug resistance.

The 32CA reactions of a series of pairs of bent three-atom-components (B-TACs) and linear TACs (L-TACs) towards electrophilic dicyanoethylene (DCE) have been studied within the Molecular Electron Density Theory in order to understand their different reactivity. ELF analysis indicates that while pseudodiradical B-TACs change their electronic structure to pseudoradical or carbenoid L-TACs upon dehydrogenation, zwitterionic B-TACs experience no remarkable change. Analysis of the CDFT indices indicates that five of the nine studied TACs have a strong nucleophilic character, thus participating in polar reactions towards electrophilic ethylenes. The activation energies of the 32CA reactions of the nine TACs towards electrophilic DCE range from 0.6 to 22.0 kcal·mol-1, which are by between 2.0 and 10.1 kcal·mol-1 lower than those involved in the non-polar 32CA reactions with ethylene. In general, B-TACs are more reactive than their L-TAC counterparts. A change of the regioselectivity is found in these polar 32CA reactions; in general, while B-TACs are meta regioselective, L-TACs are ortho regioselective. Analysis of the geometrical parameters indicates that at all TSs, the formation of the single bond involving the most electrophilic C4 carbon of DCE is more advanced than that involving the C5 one. A change of the asynchronicity in the reactions involving B-TACs and L-TACs is also found.

Abstract: DNA fragmentation factors 40 and 45 (DFF40 and DFF45) and B-cell lymphoma 2 (Bcl-2) expression were evaluated in the normal human endometrium and myometrium. DFF40, DFF45, and Bcl-2 expression was assessed via immunohistochemistry in the proliferative, secretory, and atrophic endometrium and myometrium collected postmenopausally and premenopausally during the proliferative and secretory phases of the menstrual cycle. The endometrium showed significantly higher DFF40 and DFF45 expression than that in the uterine myometrium; compared to the stroma, endometrial glands showed the highest expression in pre- and postmenopausal specimens. Glandular expression of DFF45 was dependent on the menstrual cycle, reaching its highest level in the secretory endometrium. The glandular expression of DFF40 and DFF45 was significantly lower in postmenopausal specimens than that in premenopausal tissue. No cycle-dependent changes were reported for stromal or myometrial DFF40 or DFF45 expression. Compared to the endometrial stroma and myometrium, Bcl-2 showed the highest expression in the glandular proliferative endometrium and the lowest expression in the stromal secretory endometrium and myometrium during the secretory phase of the cycle. DFF45 and Bcl-2 showed menstrual cycle-dependent expression, which was limited to the glandular layer of the endometrium.

Human epidermal growth factor receptor 2 (HER2) belongs to the ErbB family, a group of four transmembrane glycoproteins with tyrosine kinase activity, all structurally related to the epidermal growth factor receptor (EGFR). These tyrosine kinases are involved in the transmission of cellular signals controlling normal cell growth and differentiation. If this transmission goes awry, it can lead to dysregulated growth of the cell. HER2 specifically can be implicated in the pathogenesis of at least eight malignancies. HER2 positivity quickly became a well characterized indicator of aggressiveness and poor prognosis, with high rates of disease progression and mortality. After realizing the implication of HER2, it first became investigated as a target for treatment in breast cancer, and later expanded to areas of research in other cancers types. To this day, the most therapeutic advancements of anti-HER2 therapy have been in breast cancer, however, there have been strong advancements made in the incorporation of anti HER2 therapy in other cancer types as well. This comprehensive review dissects HER2 to its core incorporating the most up to date information. The topics touched upon are discussed in detail and up to 200 published sources from the most highly recognized journals have been integrated. The importance of knowing about HER2 is exemplified by the groundbreaking advancements that have been made, and the change in treatment plans it has brought to the oncological world in the last twenty years. Since, its ground breaking discovery there has been significant breakthroughs in knowledge regarding the actual receptor, the receptors biology, its mechanism of action, advancements in tests to detect HER2 and significant strides on how to best incorporate targeted treatment. Due to the success of this field thus far, the review concludes by discussing the future of novel anti-HER2 therapy currently in development that everyone should be aware of.

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.

This study aimed to compare three different extracts of Saco sweet cherry, namely non-coloured fraction, coloured fraction and total extract concerning phenolic composition, antioxidant and antidiabetic potential, erythrocytes’ protection and effects on Caco-2 cells. A total of 22 phenolic compounds were identified by LC-DAD. Hydroxycinnamic acids were the most predominant in both non-coloured fraction and total extract, while cyanidin-3-O-rutinoside was the main anthocyanin found in the coloured fraction. The total extract was the most effective against DPPH, nitric oxide and superoxide radicals, and in the inhibition of α-glucosidase enzyme. Finally, the protective effect of the extracts to prevent oxidative damage in human erythrocytes was assessed. The coloured fraction revealed the best activity against hemoglobin oxidation and hemolysis. Regarding to Caco-2 cells, the coloured extract exhibited the most cytotoxic effects, while the total extract was the most efficient in protecting these cells against oxidative damage induced by t-BHP.

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

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by pre-treatment of cells with the TG2 enzyme inhibitor cystamine. Further analysis revealed that, whereas the full-length TG2 isoform (TG2-L) was almost completely cytoplasmic in its distribution, the majority of the short TG2 isoform (TG2-S) was membrane-associated in both parental and chemoresistant HepG2 cells. Following induction of cisplatin toxicity in non-chemoresistant parental cells, TG2-S together with cisplatin quickly relocated to the cytosolic fraction. Conversely, no cytosolic relocalisation of TG2-S or nuclear accumulation cisplatin was observed following identical treatment of chemoresistant cells, where TG2-S remained predominantly membrane-associated. This suggests that deficient subcellular relocalisation of TG2-S from membranous structures into the cytoplasm may limit the apoptic response to cisplatin toxicity in chemoresistant cells. Structural analysis of TG2 revealed the presence of binding motifs for interaction of TG-S with the membrane scaffold protein LC3/LC3 homologue that could contribute to a novel mechanism of chemotherapeutic resistance in HepG2 cells.

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.

First, an introductory essay is carried out to build a historical, economic-productive and legal theoretical framework of the origin and formation of Secondary Technical Schools in Europe, North America and the Argentine Republic. Then a normative introduction to Technical Education is carried out at the Technical School No. 2 “Independencia” of Concordia, Entre Ríos, Argentine Republic. Its regulations and Laws that govern technical education. We continue analyzing the development of five (5) case studies generated in the E.E.T. No. 2 “Independence” of the city of Concordia, Province of Entre Ríos, Argentine Republic. Case study No. 1: Face masks for Covid-19, designed with CAD-STL software and printed in polylactic acid (PLA) with 3D printers, for protection from SARS-CoV-2 (Coronavirus) or Covid-19. Case study No. 2: TURBO: air extractor/blower for environments contaminated by COVID-19. Case study No. 3: ROBOT-T2: Educational Robot Made by Students and Teachers of the Technical School No. 2 (E.E.T. No. 2) “Independencia”, Concordia, Entre Ríos, Argentine Republic. Case study No. 4: Self-construction EcoBlock, for social housing. Case study No. 5: Relationships of all sciences with abductive thinking, creativity, design, art and the main relationships between Social Sciences (philosophy, logic, hermeneutic research methodology, etc.) with Exact and Natural Sciences (mathematics, physics, chemistry, biology, genetics), other sciences and disciplines such as engineering, medicine, etc. We obtain the conclusions of the development. Bibliography.

Evaluation of drug permeability using cell monolayers is an important in vitro assay in the process of drug development, to identify compounds with favourable pharmacokinetics that may proceed to in vivo studies. When allowed to differentiate on permeable filters for at least 21 days, monolayers of Caco-2 cells develop morphological and functional properties similar to those of the intestinal epithelium. Permeability through Caco-2 monolayers is thus particularly relevant to assess drug absorption after oral administration. The major drawback of this assay is its very low throughput, with the cell monolayers being used in a single permeability assay. We have previously proposed a protocol to allow the re-use of the Caco-2 monolayer on additional permeability assays during the stable period and shown that cell monolayer integrity is maintained. In this work we evaluate the effect of re-use on the permeability of several reference compounds that permeate through passive pathways and show that the cell monolayers can be re-used twice in additional permeability assays. Preliminary results were also obtained regarding active transport pathways, and a new methodology is proposed to quantify the contribution from passive and active transport. This is a major step towards the full validation of the re-use methodology proposed, which at least triplicates the throughput of this important in vitro assay.

A land cover map of two arctic catchments, nearby the Abisko Scientific Research Station, was obtained from a classification of a Sentinel-2 satellite image and a ground survey performed in July 2022. The two contiguous catchments, Miellajokka and Stordalen, are covered by various ecotypes, from boreal forest to alpine tundra and peatland. The random forests algorithm correctly identified 88% of polygon pixels reserved for testing. The developed workflow relied solely on open source software and acquired ground observations. Space organization was directed by the altitude as demonstrated by the intersection of the land cover with the topography. Comparison between this new land cover map and previous ones based on data acquired between 2008 and 2011 shows some trends of vegetation cover evolution in response to climate change in the considered area.

Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. 2’-fucosyllactose (2’-FL), a human milk oligosaccharide, has anti-inflammatory effects and plays a protective role in arterial thrombosis, but its role in ischemic stroke remains unclear. This study aimed to investigate the neuroprotective effects of 2’-FL and its potential mechanisms in a mouse model of ischemic stroke. The administration of 2’-FL led to a reduction in the size of cerebral infarct and reactive oxygen species (ROS)-related products in the brain of MCAO mice. Further, 2’-FL promotes the recovery of neurological deficits and motor function in neurological scores and behavior tests. Biochemical studies showed that 2’-FL reduced upregulated IL-10 and downregu-lated TNF-α. Additionally,2’-FL enhanced M2-type microglial polar2’-FL upregulated IL-10 and downregulated TNF-α ization at 7 days after MCAO, with an increase in IL-4 levels and STAT6 activation at 3 days after MCAO. Our data showed that 2’-FL reduced the neurological symptoms of ischemic stroke and ROS accumulation in the brain through IL-4/STAT6-dependent M2-type mi-croglial polarization in MCAO mice. These results demonstrate that 2’-FL is a potentially effective therapeutic agent for ischemic stroke.

Employing remote sensing techniques to evaluate crop residue cover (CRC) enables rapid mapping of tillage practices over large cropland areas, which has significant practical implications for monitoring the implementation of conservation tillage practices. This research utilized Sentinel-2 MSI and Landsat-8 OLI remotely sensed data, various spectral indices were calculated and the datasets were correlated with the field-measured CRC data. Selected spectral indices, highly significantly correlated, were chosen to build a correlation model between the indices and the CRC. Considering Sentinel-2 MSI and Landsat 8 OLI remotely sensed data variations in spectral and spatial scales, the accuracy of CRC models was evaluated using R2 and RMSE values. From the results, it's evident that all six spectral indices, including STI, NDTI, SRNDR, NDI5, NDI7 and NDSVI, registered correlation coefficients with the CRC exceeded 0.3 in the study area. STI and NDTI showed a stronger correlation to CRC, with coefficients of 0.810 and 0.803, respectively. For the Landsat 8 data, the lowest correlation obtained was for NDSVI with the Landsat 8 data with a correlation coefficient of 0.358. Applying the linear regression technique, STI and NDTI obtained higher accuracy compared to other indices in the Sentinel-2 MSI data. For NDTI and STI, The R2 values were 0.650 and 0.665, respectively, while their corresponding RMSE values were 3.96% and 4.03%. The highest model accuracy was obtained for the STI and NDTI constructed from the Landsat 8 OLI data (R2 values 0.41 and 0.40; RMSE values 5.25% and 5.27%, respectively). The CRC model built using partial least squares regression (PLSR) exhibited greater precision when applied to the Sentinel-2 MSI data (R2 value 0.894; RMSE value 2.18%) in comparison to the Landsat 8 OLI data (R2 value 0.695; RMSE value 3.70%). PLSR has the potential to enhance the precision of the model. In addition, the study area shows that the estimation of the CRC is better in the one-dimensional linear regression model and the PLSR model created with the Sentinel-2 MSI optical data compared to the Landsat 8 OLI optical remotely sensed data. The validation suggests that the CRC estimation in the study area is more precise when using the model relying on Sentinel-2 satellite imagery rather than the Landsat 8 OLI imagery.

Abstract: Several publications have raised the issue that the development of diabetes is preceded by alteration of the microbiome (dysbiosis) and hence, the role of environmental factors, triggering dysbiosis, should be considered. Antibiotics are powerful agents inducing dysbiosis and the authors wanted to explore the possible relationship between the consumption of different major classes of antibiotics and the prevalence of diabetes (type-1, /T1D/, type-2 /T2D/) in thirty European countries. According to our hypothesis, if such association exists, the dominant use of certain major antibiotic classes might be reflected in the prevalence of T1D and T2D in different countries. Comparisons were performed between the prevalence of diabetes (T1D and T2D) estimated for 2019 and featured in the Diabetes Atlas with the average yearly consumption of major antibiotic classes of the previous 10 years (2010-19) extracted from the ECDC yearly reports on antibiotic consumption in Europe. Pearson correlation and variance analysis were used to estimate the possible relationship. Strong, positive (enhancer) associations were found between the prevalence of T1D and the consumption of tetracycline (J01A /p: 0.001/) and the narrow spectrum penicillin (J01CE /p: 0,006/, CF /p: 0.018/). Strong negative (inhibitor) association was observed with broad-spectrum, beta-lactamase resistant penicillin (J01CR /p: 0.003/), macrolide (J01F /p: 0.008/) and quinolone (J01M /p: 0.001/). T2D showed significant positive associations with cephalosporin (J01D /p: 0.048/) and quinolone (J01M /p: 0.025/), and a non-significant negative association was detected with broad-spectrum, beta-lactamase-sensitive penicillin (J01CA /p: 0.67/). Countries with the highest prevalence of diabetes (first 10 positions) showed concordance with the higher consumption of “enhancer” and the lower consumption of “inhibitor” antibiotics (first 10 positions) as indicated by variance analysis. Countries with high prevalence of T1D showed high consumption of tetracycline (p: 0.015), and narrow spectrum, beta-lactamase sensitive penicillin (p: 0.008), and low consumption of “inhibitor” antibiotics (broad-spectrum, beta-lactamase resistant, combination penicillin (p: 0.005), cephalosporin (p: 0.036), and quinolone (p: 0.003). Countries with a high prevalence of T2D consumed more cephalosporin (p: 0.084), quinolone (p: 0.54), and less broad-spectrum, beta-lactamase sensitive penicillin (p: 0.012) than other countries. Conclusion/Interpretation: The development of diabetes-related dysbiosis might be attached to higher consumption of specific classes of antibiotics, showing positive (enhancer) associations with the prevalence of diabetes, and the low consumption of other classes of antibiotics shoving negative (inhibitory) associations. Those groups of antibiotics are different in T1D and T2D

The purpose of current study was to investigate the expression characteristic of circular RNAs (circRNAs) in peripheral blood of type 2 diabetes mellitus (T2DM) patients and their potentials as diagnostic biomarkers for pre-diabetes and T2DM. In present study, the circRNAs in the peripheral blood from 6 healthy individuals and 6 T2DM patients were collected for microarray analysis. The results indicated that there were 489 differentially expressed circRNAs, of which 78 were upregulated and 411 were downregulated in the T2DM group. Then we selected 5 circRNAs as the candidate biomarkers under a stricter screening criteria and further verified them in another cohort (control group, n=20; pre-diabetes group, n =20; T2DM group; n=20). 3 of the 5 circRNAs presented upregulated expression in the experimental groups, including 2 circRNAs of the T2DM group that had higher expression than the pre-diabetes group. Hsa_circ_0054633 was identified to have the largest area value under the carve (AUC). In another independent cohort (control group, n=60; pre-diabetes group, n=63; T2DM group, n=64), the diagnostic capacity of hsa_circ_0054633 was tested. The results showed that the AUC for the diagnosis of pre-diabetes was 0.751(95% confidence interval=[0. 666-0.835], P＜0.001) while it was 0.793 ([0.716-0.871], P＜0.001) for the diagnosis of T2DM. After including the risk factors of T2DM, the AUC increased to 0.841 ([0.773-0.910], P <0.001) and 0.834 ([0.762-0.905], P <0.001), respectively. Hsa_circ_0054633 presented a certain diagnostic capability for pre-diabetes and T2DM.

Malignant melanoma is a lethal skin cancer containing melanoma-initiating cells (MIC), implicated in tumorigenesis, invasion, and drug resistance, and characterized by elevated expression of stem cell markers, such as CD133. We previously showed that siRNA knockdown of CD133 enhances apoptosis induced by the MEK inhibitor trametinib in melanoma cells. The current study investigates underlying mechanisms of CD133’s anti-apoptotic activity in patient-derived BAKP and POT cells, harboring difficult-to-treat NRASQ61K and NRASQ61R drivers, after CRISPR-Cas9 CD133 knockdown or Dox-inducible expression of CD133. To maintain stable expression of CD133, MACS-sorted CD133(+) positive cells were expanded by ROCK-mediated conditional reprogramming of BAKP melanoma cells (BAKR). BAKR showed increased survival via reduced apoptosis after exposure to trametinib or DTIC, compared to BAKP. CRISPR-Cas9- mediated CD133 knockdown in BAKR cells (BAKR-T3) re-sensitized the cells, while CRISPR-Cas9 knockdown of CD133 in parental BAKP and POT cells even further increased trametinib-induced apoptosis (cleaved PARP) by reducing levels of anti-apoptotic BCL-xL, p-AKT, and p-BAD, and increasing pro-apoptotic BAD and active BAX. Dox-induced CD133 overexpression had the opposite effect, and blocked trametinib-induced apoptosis in both cell lines, coincident with elevated p-AKT, p-BAD, BCL-2 and BCL-xL and decreased levels of the active form of BAX and caspases-3 and -9. The roles of CD133 in AKT and BAD phosphorylation, or in the upregulation of anti-apoptotic BCL-2 family members, was further investigated by AKT knockout with siRNA, or inhibition of BCL-2 family members with navitoclax (ABT-263). Similar to CD133 knockdown, AKT1/2 siRNA knockdown in BAKP cells also reduced p-BAD. CD133 knockdown (T3)-mediated reduction of pBAD levels was equivalent in AKT-knockdown or AKT control cells indicating that CD133 may be upstream of AKT signaling. In BAKP cells treated with trametinib and/or ABT-263, effects of ABT-263 mirrored CD133 knockdown, since levels of active BAX and cleaved-PARP in BAKP-SC (CD133-) cells increased to the same level as that exhibited by BAKP-T3 cells (CD133+). CD133 may therefore activate a survival pathway where 1) increased phosphorylation of AKT induces 2) phosphorylation and inactivation of BAD, 3) decrease in the active form of BAX, and 4) reduction in caspase-mediated PARP cleavage, indicating apoptosis suppression leading to drug resistance in melanomas. Targeting survival pathways by which CD133 may confer chemoresistance in MICs can contribute to development of more effective treatments for patients with high-risk melanoma.

Prebiotic oligosaccharides are widely used as human and animal feed additives for their beneficial effects on the gut microbiota. However, there are limited data to assess the direct effect of such functional foods on the transcriptome of intestinal epithelial cells. The purpose of this study is to describe the differential transcriptomes and cellular pathways of colonic cells directly exposed to galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS). We have examined the differential gene expression of polarized Caco-2 cells treated with GOS or FOS and their respective mock-treated cells using mRNA sequencing (RNA-seq). A total of 89 significant differentially expressed genes were identified between GOS and mock-treated groups. For FOS treatment, a reduced number of 12 significant genes were observed to be differentially expressed relative to the control group. KEGG and Gene Ontology functional analysis revealed that genes up-regulated in the presence of GOS were involved in digestion and absorption processes, fatty acids and steroids metabolism, potential antimicrobial proteins, energy-dependent and -independent transmembrane trafficking of solutes and amino acids. Using our data, we have established complementary non-prebiotic modes of action for these frequently used dietary fibers.

Metabolic surgery can promote comprehensive physiological improvements to alleviate metabolic disorders, particularly for patients with type 2 diabetes. Nevertheless, the therapeutic scope has been limited owing to unexpectedly inconsistent surgical outcomes. Therefore, this study to overcome these obstacles by determining the fundamental mechanism underlying the conflicting outcomes. The surgical anatomy, clinical course, and outcomes of various metabolic surgeries, including modified duodenal-jejunal bypass (DJB) procedures, were compared to understand the specific surgical patterns from different perspectives comprehensively. Patients in the nonobese group were exclusively included to prevent confounding effects from overweight patients with type 2 diabetes. Following intestinal anastomosis, the epithelial identity of the succeeding intestine was replaced by that of the proximal epithelium owing to altered crosstalk between the epithelium and opposing mesenchymal cells. Subsequent intestinal compensatory proliferation and rapid turnover rate accelerate the spread of the replaced epithelium. The main factors contributing to inconsistent outcomes of metabolic surgery are inadequate duodenal exclusion and inappropriate biliopancreatic limb length. Replacement of enteroendocrine cells during regeneration can lead to inconsistent outcomes in metabolic surgery. The type and density of enteroendocrine cells distributed at the terminal end of the proximal intestine play a significant role in diverse outcomes of metabolic surgery.