• Weinreich Haynes opublikował 1 rok, 8 miesięcy temu

    In this report, we present a process for the fabrication and tapering of a silicon (Si) nanopillar (NP) array on a large Si surface area wafer (2-inch diameter) to provide enhanced light harvesting for Si solar cell application. From our N,N-dimethyl-formamide (DMF) solvent-controlled spin-coating method, silica nanosphere (SNS in 310 nm diameter) coating on the Si surface was demonstrated successfully with improved monolayer coverage (>95%) and uniformity. After combining this method with a reactive ion etching (RIE) technique, a high-density Si NP array was produced, and we revealed that controlled tapering of Si NPs could be achieved after introducing a two-step RIE process using (1) CHF3/Ar gases for SNS selective etching over Si and (2) Cl2 gas for Si vertical etching. From our experimental and computational study, we show that an effectively tapered Si NP (i.e., an Si nanotip (NT)) structure could offer a highly effective omnidirectional and broadband antireflection effect for high-efficiency Si solar cell application.Hypoxic tumors overexpress membrane-bound isozymes of carbonic anhydrase (CA) CA IX and CA XII, which play key roles in tumor pH homeostasis under hypoxia. Selective inhibition of these CA isozymes has the potential to generate pH imbalances that can lead to tumor cell death. Since these isozymes are dimeric, we designed a series of bifunctional PEGylated CA inhibitors (CAIs) through the attachment of our preoptimized CAI warhead 1,3,4-thiadiazole-2-sulfonamide to polyethylene glycol (PEG) backbones with lengths ranging from 1 KDa to 20 KDa via a succinyl linker. A detailed structure-thermal properties and structure-biological activity relationship study was conducted via differential scanning calorimetry (DSC) and via viability testing in 2D and 3D (tumor spheroids) cancer cell models, either CA IX positive (HT-29 colon cancer, MDA-MB 231 breast cancer, and SKOV-3 ovarian cancer) or CA IX negative (NCI-H23 lung cancer). We identified PEGylated CAIs DTP1K 28, DTP2K 23, and DTP3.4K 29, bearing short and medium PEG backbones, as the most efficient conjugates under both normoxic and hypoxic conditions, and in the tumor spheroid models. PEGylated CAIs did not affect the cell viability of CA IX-negative NCI-H23 tumor spheroids, thus confirming a CA IX-mediated cell killing for these potential anticancer agents.Neural stem cells represent a powerful tool to study molecules involved in pathophysiology of Nervous System and to discover new drugs. Although they can be cultured and expanded in vitro as a primary culture, their use is hampered by their heterogeneity and by the cost and time needed for their preparation. Here we report that mes-c-myc A1 cells (A1), a neural cell line, is endowed with staminal properties. Undifferentiated/proliferating and differentiated/non-proliferating A1 cells are able to generate neurospheres (Ns) in which gene expression parallels the original differentiation status. In fact, Ns derived from undifferentiated A1 cells express higher levels of Nestin, Kruppel-like factor 4 (Klf4) and glial fibrillary protein (GFAP), markers of stemness, while those obtained from differentiated A1 cells show higher levels of the neuronal marker beta III tubulin. Interestingly, Ns differentiation, by Epidermal Growth Factors (EGF) and Fibroblast Growth Factor 2 (bFGF) withdrawal, generates oligodendrocytes at high-yield as shown by the expression of markers, Galactosylceramidase (Gal-C) Neuron-Glial antigen 2 (NG2), Receptor-Interacting Protein (RIP) and Myelin Basic Protein (MBP). Finally, upon co-culture, Ns-A1-derived oligodendrocytes cause a redistribution of contactin-associated protein (Caspr/paranodin) protein on neuronal cells, as primary oligodendrocytes cultures, suggesting that they are able to form compact myelin. Thus, Ns-A1-derived oligodendrocytes may represent a time-saving and low-cost tool to study the pathophysiology of oligodendrocytes and to test new drugs.Ultrasound is an effective tool to detect and characterize lesions of the uterosacral ligament, parametrium, and paracervix. They may be the site of diseases such as endometriosis and the later stages of cervical cancer. Endometriosis and advanced stages of cervical cancer may infiltrate the parametrium and may also involve the ureter, resulting in a more complex surgery. New functional, surgical anatomy requires the complete diagnostic description of retroperitoneal spaces and tissues that contain vessels and nerves. Most endometriosis lesions and cervical cancer spread involve the cervical section of the uterosacral ligament, which is close to tissues, namely the parametrium and paracervix, which contain vessels and important nerves and nerve anastomoses of the inferior hypogastric plexus. Efferent fibers of the plexus travel to the rectum, uterus, rectovaginal ligament, deep vesicouterine ligament, and bladder. These efferent fibers are essential for bladder and rectal functionality so tailored nerve-sparing surgery became a standard approach for treating deep infiltrating endometriosis and cervical cancer. An accurate diagnosis by ultrasound has significant clinical impact and is important for appropriate treatment. In this article, we try to establish a common terminology between imaging diagnostic and modern surgical anatomy.Developing chemometric models from near-infrared (NIR) spectra requires the use of a representative calibration set of the entire population. Therefore, generally, the calibration procedure requires a large number of resources. For that reason, there is a great interest in identifying the most spectrally representative samples within a large population set. In this study, principal component and hierarchical clustering analyses have been compared for their ability to provide different representative calibration sets. The calibration sets generated have been used to control the technological maturity of grapes and total phenolic compounds of grape skins in red and white cultivars. Finally, the accuracy and precision of the models obtained with these calibration sets resulted from the application of the selection algorithms studied have been compared with each other and with the whole set of samples using an external validation set. Most of the standard errors of prediction (SEP) in external validation obtained from the reduced data sets were not significantly different from those obtained using the whole data set. Moreover, sample subsets resulting from hierarchical clustering analysis appear to produce slightly better results.In the 2015 excavation season, an east-west oriented burial (2015-Grave-14) built with large dimension stone blocks was unearthed on the south edge of „Area IVi” at the Balatlar Church in Sinop, on the northeastern Black Sea coast of Turkey. In this grave, which is dated between the end of the 6th century AD and the first half of the 7th century AD, a human skeleton was found with the head to the west and a cat skeleton was carefully placed next to the right femur. This study on the burial and the cat skeleton within it shows that, compared to the Roman period, the status of cats reached a higher level during the Byzantine period. It was found that alongside of being a pet, the Balatlar cat was a young healthy female individual that instinctively hunted rodents and birds, given that the remains of a rat and a sparrow were found in the region of the abdominal cavity, corresponding with the stomach location in the living animal. The grave presents the most significant direct archaeological evidence of a pet-human bond recorded at any Byzantine site so far.We tested whether maternal energy supplementation during the last third of gestation improves birth weight, neonatal wellbeing, and mother-young bonding. Thirty-six pregnant French Alpine goats were randomly allocated among three nutritional treatments for the last third of pregnancy (i) Control, fed alfalfa (T-0; n = 12); (ii) alfalfa + 150 g/head daily energy concentrate (T-150; n = 12); (iii) alfalfa + 300 g/head daily energy concentrate (T-300; n = 12). At birth, we collected progeny data on birth weight, birth type, sex, rectal temperature, heart rate, respiratory rate, time to standing, time to udder connection, and time to first feeding. For the dams, we collected data on the duration of labor, time to clean the progeny, and time to allow first suckling. At birth, body weight, rectal temperature, heart rate, and the respiratory rate did not differ among treatments (p > 0.05). In the dams, labor duration was not affected by the treatments (p > 0.05). The T-150 dams were faster to clean the newborn and allow first suckling (p less then 0.05). The T-150 progeny were faster to stand and the T-300 progeny were faster to connect to the udder (p less then 0.05). We conclude that energy supplementation of the dam during the last third of gestation does not affect the birth weight of the progeny, but enhances the mother-young bonding.Risky play is challenging, exciting play with the possibility of physical, social, or emotional harm. Through risky play, children learn, develop, and experience wellbeing. Children with disabilities have fewer opportunities than their typically developing peers to engage in this beneficial type of play. Our team designed a novel, school-based intervention to address this disparity; however, our intervention yielded unexpected quantitative results. In the present study, we qualitatively examined divergent results at two of the five schools that participated in the intervention. Specifically, we aimed to explore how staff culture (i.e., shared beliefs, values, and practices) influenced the intervention. To explore this relationship, we employed a retrospective, qualitative, multiple case study. We used thematic analysis of evaluative interviews with staff members to elucidate the cultures at each school. Then, we used cross-case analysis to understand the relationships between aspects of staff culture and the intervention’s implementation and results. We found that staff cultures around play, risk, disability influenced the way, and the extent to which, staff were willing to let go and allowed children to engage in risky play. Adults’ beliefs about the purpose of play and recess, as well as their expectations for children with disabilities, particularly influenced the intervention. Furthermore, when the assumptions of the intervention and the staff culture did not align, the intervention could not succeed. The results of this study highlight the importance of (1) evaluating each schools’ unique staff culture before implementing play-focused interventions and (2) tailoring interventions to meet the needs of individual schools.Characterization of potential chemical-induced developmental neurotoxicity (DNT) hazard is considered for risk assessment purposes by many regulatory sectors. However, due to test complexity, difficulty in interpreting results and need of substantial resources, the use of the in vivo DNT test guidelines has been limited and animal data on DNT are scarce. To address challenging endpoints such as DNT, the Organisation for Economic Co-Operation and Development (OECD) chemical safety program has been working lately toward the development of integrated approaches for testing and assessment (IATA) that rely on a combination of multiple layers of data (e.g., in vitro, in silico and non-mammalian in vivo models) that are supported by mechanistic knowledge organized according to the adverse outcome pathway (AOP) framework. In 2017, the OECD convened a dedicated OECD expert group to develop a guidance document on the application and interpretation of data derived from a DNT testing battery that relies on key neurodevelopmental processes and is complemented by zebrafish assays. This review will provide a brief overview of the OECD DNT project and summarize various achievements of relevance to the project. The review also presents an opportunity to describe considerations for uptake of the DNT in an in vitro battery in a regulatory context.Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug induced hypersensitivity (DiHS) syndrome is a severe delayed hypersensitivity reaction with potentially fatal consequences. Whilst recognised as T cell-mediated, our understanding of the immunopathogenesis of this syndrome remains incomplete. Here, we discuss models of DRESS, including the role of human leukocyte antigen (HLA) and how observations derived from new molecular techniques adopted in key studies have informed our mechanism-based understanding of the central role of Herpesviridae reactivation and heterologous immunity in these disorders.The effect of relative humidity (RH) and degree of sulfonation (DS) on the ionic conductivity and water uptake of proton-exchange membranes based on sulfonated multiblock copolymers composed of polysulfone (PSU) and polyphenylsulfone (PPSU) is examined experimentally and numerically. Three membranes with a different DS and ion-exchange capacity are analyzed. The heterogeneous structure of the membranes shows a random distribution of sulfonated (hydrophilic) and non-sulfonated (hydrophobic) domains, whose proton conductivity is modeled based on percolation theory. The mesoscopic model solves simplified Nernst-Planck and charge conservation equations on a random cubic network. Good agreement is found between the measured ionic conductivity and water uptake and the model predictions. The ionic conductivity increases with RH due to both the growth of the hydrated volume available for conduction and the decrease of the tortuosity of ionic transport pathways. Moreover, the results show that the ionic conductivity increases nonlinearly with DS, experiencing a strong rise when the DS is varied from 0.45 to 0.70, even though the water uptake of the membranes remains nearly the same. In contrast, the increase of the ionic conductivity between DS=0.70 and DS=0.79 is significantly lower, but the water uptake increases sharply. This is explained by the lack of microphase separation of both copolymer blocks when the DS is exceedingly high. Encouragingly, the copolymer membranes demonstrate a similar performance to Nafion under well hydrated conditions, which can be further optimized by a combination of numerical modeling and experimental characterization to develop new-generation membranes with better properties.This study aimed to examine the emotional responses evoked by cooked colored rice and its health functionality information in both consumers who eat rice as a staple food and consumers who do not eat rice as a staple food. Specifically, Korean and American consumers were exposed to colored rice and its health functionality information and an emotion lexicon was generated and measured based on focus group interviews (FGI) and two online consumer surveys. In test 1, the emotions evoked by presentation of stimuli to Koreans (N = 10) and Americans (N = 10) were extracted through FGIs and the first online consumer survey (Koreans = 69; Americans = 68) and an emotion lexicon was generated. As a result, a total of 34 terms were confirmed. Test 2 was conducted during the second online consumer survey (capturing data from a total of 208 Koreans and 208 Americans), utilizing the terms generated in test 1. In this test, only the colors (CO) of colored rice were presented to one group, while colors and health functionality information (CO&H) were presented to the other group. The overall liking for stimuli in both countries was highly correlated with familiarity. Koreans showed significantly more familiarity and liking for CO of white and black CO rice, while Americans showed significantly more familiarity and liking for CO of white and yellow rice. Hierarchical cluster analysis was performed to categorize the emotion terms, and the emotion terms were sorted into the three clusters, „Positive”, „Negative”, and „New”, for both countries. Under informed conditions, the emotions became more positive, and emotions in the „New” cluster were evoked in both countries. The current study employed a cross-cultural approach to assess consumers’ emotional responses to colored rice and health functionality information. Our findings suggest that providing foods with preferred colors for each culture and providing sufficient information on the said foods will help to promote unfamiliar foods.The combination of in vitro maturation (IVM) techniques and oocyte vitrification (OV) could increase the number of useful oocytes in different types of patients. IVM and subsequent OV is the most widely used clinical strategy. Would the results improve if we reverse the order of the techniques? Here, we evaluated survival, in vitro maturation, time to extrude the first polar body (PB), and the metaphase plate configuration of human prophase I (GV) oocytes before or after their vitrification. Specific, 195 GV oocytes from 104 patients subjected to controlled ovarian stimulation cycles were included. We stablished three experimental groups GV oocytes vitrified and IVM (Group GV-Vit), GV oocytes IVM and vitrified at MII stage (Group MII-Vit), and GV oocytes IVM (Group not-Vit). All of them were in vitro matured for a maximum of 48 h and fixed to study the metaphase plate by confocal microscopy. According to our results, the vitrification of immature oocytes and their subsequent maturation presented similar survival, maturation, and metaphase plate conformation rates, but a significantly higher percentage of normal spindle than the standard strategy. Additionally, the extension of IVM time to 48 h did not seem to negatively affect the oocyte metaphase plate configuration.We propose a detection-based tracking system for automatically processing maritime ship inspection videos and predicting suspicious areas where cracks may exist. This system consists of two stages. Stage one uses a state-of-the-art object detection model, i.e., RetinaNet, which is customized with certain modifications and the optimal anchor setting for detecting cracks in the ship inspection images/videos. Stage two is an enhanced tracking system including two key components. The first component is a state-of-the-art tracker, namely, Channel and Spatial Reliability Tracker (CSRT), with improvements to handle model drift in a simple manner. The second component is a tailored data association algorithm which creates tracking trajectories for the cracks being tracked. This algorithm is based on not only the intersection over union (IoU) of the detections and tracking updates but also their respective areas when associating detections to the existing trackers. Consequently, the tracking results compensate for the detection jitters which could lead to both tracking jitter and creation of redundant trackers. Our study shows that the proposed detection-based tracking system has achieved a reasonable performance on automatically analyzing ship inspection videos. It has proven the feasibility of applying deep neural network based computer vision technologies to automating remote ship inspection. The proposed system is being matured and will be integrated into a digital infrastructure which will facilitate the whole ship inspection process.Nematodes belonging to the genus Capillaria infect a range of domestic and wild animals. Capillariaaerophila and Capillariaboehmi cause respiratory parasitoses in dogs and wild carnivores, e.g., foxes and mustelids, although they are often overlooked in canine clinical practice. The present report describes an unusual case of a severe and mixed infection by C.aerophila and C.boehmi in a privately housed dog that showed acute and life-threatening respiratory and neurological signs. Clinic-pathologic and epizootiological implications are described and discussed.Only a small fraction of hereditary breast and/or ovarian cancer (HBOC) cases are caused by germline variants in the high-penetrance breast cancer 1 and 2 genes (BRCA1 and BRCA2). BRCA1-associated ring domain 1 (BARD1), nuclear partner of BRCA1, has been suggested as a potential HBOC risk gene, although its prevalence and penetrance are variable according to populations and type of tumor. We aimed to investigate the prevalence of BARD1 truncating variants in a cohort of patients with clinical suspicion of HBOC. A comprehensive BARD1 screening by multigene panel analysis was performed in 4015 unrelated patients according to our regional guidelines for genetic testing in hereditary cancer. In addition, 51,202 Genome Aggregation Database (gnomAD) non-Finnish, non-cancer European individuals were used as a control population. In our patient cohort, we identified 19 patients with heterozygous BARD1 truncating variants (0.47%), whereas the frequency observed in the gnomAD controls was 0.12%. We found a statistically significant association of truncating BARD1 variants with overall risk (odds ratio (OR) = 3.78; CI = 2.10-6.48; p = 1.16 × 10-5). This association remained significant in the hereditary breast cancer (HBC) group (OR = 4.18; CI = 2.10-7.70; p = 5.45 × 10-5). Furthermore, deleterious BARD1 variants were enriched among triple-negative BC patients (OR = 5.40; CI = 1.77-18.15; p = 0.001) compared to other BC subtypes. Our results support the role of BARD1 as a moderate penetrance BC predisposing gene and highlight a stronger association with triple-negative tumors.For the first time, hybrid molecules were synthesized on the basis of lithocholic and (5Z,9Z)-1,14-tetradeca-5,9-dienedicarboxylic acids, obtained in two stages using the homo-cyclomagnesiation reaction of 2-(hepta-5,6-diene-1-yloxy)tetrahydro-2H-pyran at the key stage. The resulting hybrid molecules containing 5Z,9Z-dienoic acids are of interest as novel synthetic biologically active precursors to create modern drugs for the treatment of human oncological diseases. The synthesized hybrid molecules were found to exhibit extremely high in vitro inhibitory activity against human topoisomerase I, which is 2-4 times higher than that of camptothecin, a known topoisomerase I inhibitor. Using flow cytometry and fluorescence microscopy, it was first shown that these new molecules are efficient apoptosis inducers in HeLa, U937, Jurkat, K562, and Hek293 cell cultures. In addition, the results of investigations into the effect of the synthesized acids on mitochondria and studies of possible DNA damage in Jurkat tumor cells are also presented.Nakalanga syndrome is a clinical manifestation of onchocerciasis-associated epilepsy characterized by stunting, delayed or absent secondary sexual development and skeletal deformities, and is often accompanied by epileptic seizures. The pathophysiology of Nakalanga syndrome is unknown. Here, we describe the post-mortem findings of a 17-year-old female who died with Nakalanga syndrome in northern Uganda. Macroscopic and histopathological examination of all major organs (liver, lungs, kidney and heart), including the brain and the pituitary gland, was performed. The suspected cause of death was malaria, and all major organs and pituitary gland appeared normal, except the lungs, which were edematous consistent with the malaria. Neuropathological changes include signs of neuro-inflammation (gliosis and activated microglia), which co-localized with tau-reactive neurofibrillary tangles and threads. The pathology was most abundant in the frontal cortex, thalamic and hypothalamic regions, and mesencephalon. The choroid plexus showed psammoma bodies. These findings indicate accelerated aging, probably due to repeated seizures. The neuropathological findings were similar to other persons who died with onchocerciasis-associated epilepsy. Examination of the pituitary gland did not reveal new information concerning the underlying pathophysiological mechanism of Nakalanga syndrome. Therefore, more post-mortem studies should be performed.Elastin-like polypeptides (ELPs) undergo a characteristic phase transition in response to ambient temperature. Therefore, it has been be used as a thermosensitive vector for the delivery of chemotherapy agents since it can be used to target hyperthermic tumors. This novel strategy introduces unprecedented options for treating cancer with fewer concerns about side effects. In this study, the ELP system was further modified with an enzyme-cleavable linker in order to release drugs within tumors. This system consists of an ELP, a matrix metalloproteinase (MMP) substrate, a cell-penetrating peptide (CPP), and a 6-maleimidocaproyl amide derivative of doxorubicin (Dox). This strategy shows up to a 4-fold increase in cell penetration and results in more death in breast cancer cells compared to ELP-Dox. Even in doxorubicin-resistant cells (NCI/ADR and MES-SA/Dx5), ELP-released cell-penetrating doxorubicin demonstrated better membrane penetration, leading to at least twice the killing of resistant cells compared to ELP-Dox and free Dox. MMP-digested CPP-Dox showed better membrane penetration and induced more cancer cell death in vitro. This CPP-complexed Dox released from the ELP killed even Dox-resistant cells more efficiently than both free doxorubicin and non-cleaved ELP-CPP-Dox.Tropisms are essential responses of plants, orienting growth according to a wide range of stimuli. Recently, considerable attention has been paid to root tropisms, not only to improve cultivation systems, such as those developed for plant-based life support systems for future space programs, but also to increase the efficiency of root apparatus in water and nutrient uptake in crops on Earth. To date, the Cholodny-Went theory of differential auxin distribution remains the principal tropistic mechanism, but recent findings suggest that it is not generally applicable to all root tropisms, and new molecular pathways are under discussion. Therefore, an in-depth understanding of the mechanisms and functions underlying root tropisms is needed. Contributions to this special issue aimed to embrace reviews and research articles that deepen molecular, physiological, and anatomical processes orchestrating root tropisms from perception of the stimulus to bending. The new insights will help in elucidating plant-environment interactions, providing potential applications to improve plant growth on Earth and in space where microgravity diminishes or nullifies the gravitropism dominance.The present study aimed to define the physical function and lipid profile for physical and cognitive frailty in community-dwelling Korean older adults. A total of 229 participants (age = 76.76 ± 3.72 years; body mass index = 24.83 ± 3.15) were classified into four groups robust, pre-frailty, cognitive decline, and cognitive frailty. An analysis on the four groups was performed to measure their physical and cognitive function, as well as blood biomarkers. The area under (AUC) the receiver operating characteristic curve (ROC) indicated that the 6-min Walk Test (6MWT), Timed Up and Go test (TUG), and Five Times Sit-to-Stand test (FTSS) had the potential to distinguish the capacity of an old adult to predict cognitive frailty. The 6MWT had a higher sensitivity and the TUG and FTSS tests had greater specificity. With cognitive frailty as a categorical variable, cognitive frailty status was a significant predictor of the TUG (odds ratio (OR) 2.897; 95% confidence interval (CI), 1.283-6.541), FTSS (OR 3.337; 95% CI 1.451-7.673), and 6MWT (OR 0.204; 95% CI 0.070-0.591) tests. Our findings indicate that the 6MWT, TUG, and FTSS tests are closely related to cognitive frailty and can provide potential prognostic cutoff points.Nucleotides released by smooth muscle cells (SMCs) and by innervating nerve terminals activate specific P2 receptors and modulate bladder contraction. We hypothesized that cell surface enzymes regulate SMC contraction in mice bladder by controlling the concentration of nucleotides. We showed by immunohistochemistry, enzymatic histochemistry, and biochemical activities that nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) and ecto-5′-nucleotidase were the major ectonucleotidases expressed by SMCs in the bladder. RT-qPCR revealed that, among the nucleotide receptors, there was higher expression of P2X1, P2Y1, and P2Y6 receptors. Ex vivo, nucleotides induced a more potent contraction of bladder strips isolated from NTPDase1 deficient (Entpd1-/-) mice compared to wild type controls. The strongest responses were obtained with uridine 5′-triphosphate (UTP) and uridine 5′-diphosphate (UDP), suggesting the involvement of P2Y6 receptors, which was confirmed with P2ry6 -/- bladder strips. Interestingly, this response was reduced in female bladders. Our results also suggest the participation of P2X1, P2Y2 and/or P2Y4, and P2Y12 in these contractions. A reduced response to the thromboxane analogue U46619 was also observed in wild type, Entpd1 -/- , and P2ry6 -/- female bladders showing another difference due to sex. In summary, NTPDase1 modulates the activation of nucleotide receptors in mouse bladder SMCs, and contractions induced by P2Y6 receptor activation were weaker in female bladders.Parental feeding practices and mealtime routine significantly influence a child’s eating behavior. The aim of this study was to investigate the mealtime environment in healthy children and children with gastrointestinal diseases. We conducted a cross-sectional case-control study among 787 healthy, typically developing children and 141 children with gastrointestinal diseases, aged two to seven years. Parents were asked to provide data on demographics and describe their mealtime environment by answering to 24 closed-ended questions. It was found that the majority of the children had the same number of meals every day and at the same hour. Parents of both groups exerted considerable control on the child’s food intake by deciding both when and what their child eats. Almost one third of the parents also decided how much their child eats. The two groups differed significantly in nine of the 24 questions. The study showed that both groups provided structured and consistent mealtime environments. However, a significant proportion of children did not control how much they eat which might impede their ability to self-regulate eating. The presence of a gastrointestinal disease was found to be associated with reduced child autonomy, hampered hunger cues and frequent use of distractions during meals.Melanomas are genetically and metabolically heterogeneous, which influences therapeutic efficacy and contributes to the development of treatment resistance in patients with metastatic disease. Metabolite phenotyping helps to better understand complex metabolic diseases, such as melanoma, and facilitates the development of novel therapies. Our aim was to characterize the tumor and plasma metabolomes of mice bearing genetically different melanoma xenografts. We engrafted the human melanoma cell lines A375 (BRAF mutant), WM47 (BRAF mutant), WM3000 (NRAS mutant), and WM3311 (BRAF, NRAS, NF1 triple-wildtype) and performed a broad-spectrum targeted metabolomics analysis of tumor and plasma samples obtained from melanoma-bearing mice as well as plasma samples from healthy control mice. Differences in ceramide and phosphatidylcholine species were observed between melanoma subtypes irrespective of the genetic driver mutation. Furthermore, beta-alanine metabolism differed between melanoma subtypes and was significantly enriched in plasma from melanoma-bearing mice compared to healthy mice. Moreover, we identified beta-alanine, p-cresol sulfate, sarcosine, tiglylcarnitine, two dihexosylceramides, and one phosphatidylcholine as potential melanoma biomarkers in plasma. The present data reflect the metabolic heterogeneity of melanomas but also suggest a diagnostic biomarker signature for melanoma screening.The statistical experimental design (DoE) and optimization (Response Surface Methodology combined with Box-Behnken design) of sunflower oil transesterification catalyzed by waste chicken eggshell-based catalyst were conducted in a custom-made microreactor at 60 °C. The catalyst was synthesized by the hydration-dehydration method and subsequent calcination at 600 °C. Comprehensive characterization of the obtained catalyst was conducted using X-ray powder diffractometry (XRD), X-ray fluorescence (XRF), Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), N2 physisorption, and Hg-porosimetry. Structural, morphological, and textural results showed that the obtained catalyst exhibited high porosity and regular dispersity of plate-like CaO as an active species. The obtained optimal residence time, catalyst concentration, and methanol/oil volume ratio for the continuous reaction in microreactor were 10 min, 0.1 g g-1, and 31, respectively. The analysis of variance (ANOVA) showed that the obtained reduced quadratic model was adequate for experimental results fitting. The reaction in the microreactor was significantly intensified compared to a conventional batch reactor, as seen through the fatty acid methyl esters (FAMEs) content after 10 min, which was 51.2% and 18.6%, respectively.Tumor-infiltrating CD8+ T cells have been shown to play a crucial role in controlling tumor progression. However, the recruitment and activation of these immune cells at the tumor site are strictly dependent on several factors, including the presence of dendritic cells (DCs), the main orchestrators of the antitumor immune responses. Among the various DC subsets, the role of cDC1s has been demonstrated in several preclinical experimental mouse models. In addition, the high density of tumor-infiltrating cDC1s has been associated with improved survival in many cancer patients. The ability of cDC1s to modulate antitumor activity depends on their interaction with other immune populations, such as NK cells. This evidence has led to the development of new strategies aimed at increasing the abundance and activity of cDC1s in tumors, thus providing attractive new avenues to enhance antitumor immunity for both established and novel anticancer immunotherapies. In this review, we provide an overview of the various subsets of DCs, focusing in particular on the role of cDC1s, their ability to interact with other intratumoral immune cells, and their prognostic significance on solid tumors. Finally, we outline key therapeutic strategies that promote the immunogenic functions of DCs in cancer immunotherapy.Rapid improvements in cancer survival led to the realization that many modalities used to treat or control cancer may cause accelerated aging in cancer survivors. Clinically, „accelerated aging” phenotypes in cancer survivors include secondary cancers, frailty, chronic organ dysfunction, and cognitive impairment, all of which can impact long-term health and quality of life in cancer survivors. The treatment-induced accelerated aging in cancer survivors could be explained by telomere attrition, cellular senescence, stem cell exhaustion, DNA damage, and epigenetic alterations. Several aging clocks and biomarkers of aging have been proposed to be potentially useful in estimating biological age, which can provide specific information about how old an individual is biologically independent of chronological age. Measuring biological age in cancer survivors may be important for two reasons. First, it can better predict the risk of cancer treatment-related comorbidities than chronological age. Second, biological age may provide additional value in evaluating the effects of treatments and personalizing cancer therapies to maximize efficacy of treatment. A deeper understanding of treatment-induced accelerated aging in individuals with cancer may lead to novel strategies that reduce the accelerated aging and improve the quality of life in cancer survivors.Uveitis is a vision inflammatory disorder with a high prevalence in developing countries. Currently, marketed treatments remain limited and reformulation is usually performed to obtain a tacrolimus eye drop as a therapeutic alternative in corticosteroid-refractory eye disease. The aim of this work was to develop a mucoadhesive, non-toxic and stable topical ophthalmic formulation that can be safely prepared in hospital pharmacy departments. Four different ophthalmic formulations were prepared based on the tacrolimus/hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complexes’ formation. Phase solubility diagrams, Nuclear Magnetic Resonance (NMR) and molecular modeling studies showed the formation of 11 and 12 tacrolimus/HPβCD inclusion complexes, being possible to obtain a 0.02% (w/v) tacrolimus concentration by using 40% (w/v) HPβCD aqueous solutions. Formulations also showed good ophthalmic properties in terms of pH, osmolality and safety. Stability studies proved these formulations to be stable for at least 3 months in refrigeration. Ex vivo bioadhesion and in vivo ocular permanence showed good mucoadhesive properties with higher ocular permanence compared to the reference pharmacy compounding used in clinical settings (t1/2 of 86.2 min for the eyedrop elaborated with 40% (w/v) HPβCD and Liquifilm® versus 46.3 min for the reference formulation). Thus, these novel eye drops present high potential as a safe alternative for uveitis treatment, as well as a versatile composition to include new drugs intended for topical ophthalmic administration.The clinical course of chronic lymphocytic leukemia (CLL) is very ambiguous, showing either an indolent nature of the disease or having latent dangerous progression, which, if diagnosed, will require an urgent therapy. The prognosis of the course of the disease and the estimation of the time of therapy initiation are crucial for the selection of a successful treatment strategy. A reliable estimating index is needed to assign newly diagnosed CLL patients to the prognostic groups. In this work, we evaluated the comparative expressions of proteins in CLL blood cells using a label-free quantification by mass spectrometry and calculated the integrated proteomic indexes for a group of patients who received therapy after the blood sampling over different periods of time. Using a two-factor linear regression analysis based on these data, we propose a new pipeline for evaluating model development for estimation of the moment of therapy initiation for newly diagnosed CLL patients.After obtaining the value of shear wave velocity (VS) from the bender elements test (BET), the shear modulus of soils at small strains (Gmax) can be estimated. Shear wave velocity is an important parameter in the design of geo-structures subjected to static and dynamic loading. While bender elements are increasingly used in both academic and commercial laboratory test systems, there remains a lack of agreement when interpreting the shear wave travel time from these tests. Based on the test data of 12 Warsaw glacial quartz samples of sand, primarily two different approaches were examined for determining VS. They are both related to the observation of the source and received BE signal, namely, the first time of arrival and the peak-to-peak method. These methods were performed through visual analysis of BET data by the authors, so that subjective travel time estimates were produced. Subsequently, automated analysis methods from the GDS Bender Element Analysis Tool (BEAT) were applied. Here, three techniques in the time-domain (TD) were selected, namely, the peak-to-peak, the zero-crossing, and the cross-correlation function. Additionally, a cross-power spectrum calculation of the signals was completed, viewed as a frequency-domain (FD) method. Final comparisons between subjective observational analyses and automated interpretations of BET results showed good agreement. There is compatibility especially between the two methods the first time of arrival and the cross-correlation, which the authors considered the best interpreting techniques for their soils. Moreover, the laboratory tests were performed on compact, medium, and well-grained sand samples with different curvature coefficient and mean grain size. Investigation of the influence of the grain-size characteristics of quartz sand on shear wave velocity demonstrated that VS is larger for higher values of the uniformity coefficient, while it is rather independent of the curvature coefficient and the mean grain size.Micronutrient deficiencies remain a serious nutritional concern in Bangladesh, especially among rural women of reproductive age (WRA). This study assesses the diet quality of reproductive-aged adolescent girls and adult women (referred to together as WRA in this study), including socio-demographic factors associated with their diet quality. The diet quality of adolescent girls was compared with that of adult women to assess which group was most at risk. The diet quality was measured by calculating the nutrient adequacy ratio (NAR), using the preceding 24 h dietary recall method. The mean adequacy ratio (MAR) was calculated as an overall measure of diet quality using the NAR. Nearly three quarters of WRA (adolescents 73.1-88.5%; adult women 72.9-86.4%) had an inadequate intake of calcium, vitamin A, folic acid, and vitamin B12. The prevalence of inadequate dietary intakes of calcium, zinc, and energy was significantly higher in adolescent girls (p less then 0.001) than in adult women. Overall diet quality was significantly better in adult women (0.51 ± 0.21, p less then 0.001) than in adolescent girls (0.49 ± 0.22). Age, marital status, educational level, and monthly household income were important factors associated with the diet quality of WRA. Micronutrient inadequacy is widely prevalent in the diets of WRA in Bangladesh, and adolescent girls with poor socio-economic status and lower educational levels are at higher risk.Four new bis(tpy) unimers with different linkers between the thieno[3,2-b]thiophene-2,5-diyl central unit and terpyridine-4′-yl (tpy) end-groups no linker (Tt), ethynediyl (TtE), 1,4-phenylene (TtPh) and 2,2′-bithophene-5,5′-diyl (TtB) are prepared, characterized, and assembled with Fe2+ ions to metallo-supramolecular polymers (Fe-MSPs). The Fe-MSP films prepared by spin-casting on Indium Tin Oxide (ITO) glass are characterized by atomic force microscope (AFM) microscopy, cyclic voltammetry, and UV/vis spectroscopy and studied for their electrochromism and effect of the unimer structure on their electrochromic performance. Of the studied MSPs, Fe-Tt shows the highest optical contrast as well as coloration efficiency (CE = 641 cm2 C-1) and the fastest optical response. This makes it an excellent candidate for possible use in electrochromic devices.We have previously reported that histone deacetylase epigenetic regulator Hdac1 and Hdac2 deletion in intestinal epithelial cells (IEC) disrupts mucosal tissue architecture and barrier, causing chronic inflammation. In this study, proteome and transcriptome analysis revealed the importance of signaling pathways induced upon genetic IEC-Hdac1 and Hdac2 deletion. Indeed, Gene Ontology biological process analysis of enriched deficient IEC RNA and proteins identified common pathways, including lipid metabolic and oxidation-reduction process, cell adhesion, and antigen processing and presentation, related to immune responses, correlating with dysregulation of major histocompatibility complex (MHC) class II genes. Top upstream regulators included regulators associated with environmental sensing pathways to xenobiotics, microbial and diet-derived ligands, and endogenous metabolites. Proteome analysis revealed mTOR signaling IEC-specific defects. In addition to mTOR, the STAT and Notch pathways were dysregulated specifically in jejunal IEC. To determine the impact of pathway dysregulation on mutant jejunum alterations, we treated mutant mice with Tofacitinib, a JAK inhibitor. Treatment with the inhibitor partially corrected proliferation and tight junction defects, as well as niche stabilization by increasing Paneth cell numbers. Thus, IEC-specific histone deacetylases 1 (HDAC1) and 2 (HDAC2) support intestinal homeostasis by regulating survival and translation processes, as well as differentiation and metabolic pathways. HDAC1 and HDAC2 may play an important role in the regulation of IEC-specific inflammatory responses by controlling, directly or indirectly, the JAK/STAT pathway. IEC-specific JAK/STAT pathway deregulation may be, at least in part, responsible for intestinal homeostasis disruption in mutant mice.Saccharomyces yeasts are widely distributed in the environment and microbiota of higher organisms. The killer phenotype of yeast, encoded by double-stranded RNA (dsRNA) virus systems, is a valuable trait for host survival. The mutual relationship between the different yet clearly defined LA and M virus pairs suggests complex fitting context. To define the basis of this compatibility, we established a system devoted to challenging inherent yeast viruses using viral proteins expressed in trans. Virus exclusion by abridged capsid proteins was found to be complete and nonspecific, indicating the presence of generic mechanisms of Totiviridae maintenance in yeast cells. Indications of specificity in both the exclusion of LA viruses and the maintenance of M viruses by viral capsid proteins expressed in trans were observed. This precise specificity was further established by demonstrating the importance of the satellite virus in the maintenance of LA virus, suggesting the selfish behavior of M dsRNA.Sulfaquinoxaline (SQX) has been detected in environmental water samples, where its side effects are still unknown. To the best of our knowledge, its oxidation by Fenton and photo-Fenton processes has not been previously reported. In this study, SQX oxidation, mineralization, and toxicity (Escherichia coli and Staphylococcus aureus bacteria) were evaluated at two different setups laboratory bench (2 L) and pilot plant (15 L). The experimental design was used to assess the influence of the presence or absence of radiation source, as well as different H2O2 concentrations (94.1 to 261.9 mg L-1). The experimental conditions of both setups were SQX = 25 mg L-1, Fe(II) = 10 mg L-1, pH 2.8 ± 0.1. Fenton and photo-Fenton were suitable for SQX oxidation and experiments resulted in higher SQX mineralization than reported in the literature. For both setups, the best process was the photo-Fenton (178.0 mg L-1 H2O2), for which over 90% of SQX was removed, over 50% mineralization, and bacterial growth inhibition less than 13%. In both set-ups, the presence or absence of radiation was equally important for sulfaquinoxaline oxidation; however, the degradation rates at the pilot plant were between two to four times higher than the obtained at the laboratory bench.The loss of redox homeostasis induced by hyperglycemia is an early sign and key factor in the development of diabetic retinopathy. Due to the high level of long-chain polyunsaturated fatty acids, diabetic retina is highly susceptible to lipid peroxidation, source of pathophysiological alterations in diabetic retinopathy. Previous studies have shown that pterostilbene, a natural antioxidant polyphenol, is an effective therapy against diabetic retinopathy development, although its protective effects on lipid peroxidation are not well known. Plasma, urine and retinas from diabetic rabbits, control and diabetic rabbits treated daily with pterostilbene were analyzed. Lipid peroxidation was evaluated through the determination of derivatives from arachidonic, adrenic and docosahexaenoic acids by ultra-performance liquid chromatography coupled with tandem mass spectrometry. Diabetes increased lipid peroxidation in retina, plasma and urine samples and pterostilbene treatment restored control values, showing its ability to prevent early and main alterations in the development of diabetic retinopathy. Through our study, we are able to propose the use of a derivative of adrenic acid, 17(RS)-10-epi-SC-Δ15-11-dihomo-IsoF, for the first time, as a suitable biomarker of diabetic retinopathy in plasmas or urine.The Warburg effect has immensely succored the study of cancer biology, especially in highlighting the role of mitochondria in cancer stemness and their benefaction to the malignancy of oxidative and glycolytic cancer cells. Mitochondrial genetics have represented a focal point in cancer therapeutics due to the involvement of mitochondria in programmed cell death. The mitochondrion has been well established as a switch in cell death decisions. The mitochondrion’s instrumental role in central bioenergetics, calcium homeostasis, and translational regulation has earned it its fame in metastatic dissemination in cancer cells. Here, we revisit and review mechanisms through which mitochondria influence oncogenesis and metastasis by underscoring the oncogenic mitochondrion that is capable of transferring malignant capacities to recipient cells.Dryland xeric conditions exert a deterministic effect on microbial communities, forcing life into refuge niches. Deposited rocks can form a lithic niche for microorganisms in desert regions. Mineral weathering is a key process in soil formation and the importance of microbial-driven mineral weathering for nutrient extraction is increasingly accepted. Advances in geobiology provide insight into the interactions between microorganisms and minerals that play an important role in weathering processes. In this study, we present the examination of the microbial diversity in dryland rocks from the Tsauchab River banks in Namibia. We paired culture-independent 16S rRNA gene amplicon sequencing with culture-dependent (isolation of bacteria) techniques to assess the community structure and diversity patterns. Bacteria isolated from dryland rocks are typical of xeric environments and are described as being involved in rock weathering processes. For the first time, we extracted extra- and intracellular DNA from rocks to enhance our understanding of potentially rock-weathering microorganisms. We compared the microbial community structure in different rock types (limestone, quartz-rich sandstone and quartz-rich shale) with adjacent soils below the rocks. Our results indicate differences in the living lithic and sublithic microbial communities.The relationship between activation of the sympathetic nervous system and cardiac hypertrophy has long been known. However, the molecular genetic basis of this association is poorly understood. Given the known role of hypothalamic norepinephrine in the activation of the sympathetic nervous system, the aim of the work was to carry out genetic mapping using Quantitative Trait Loci (QTL) analysis and determine the loci associated both with an increase in the concentration of norepinephrine in the hypothalamus and with an increase in heart mass in Inherited Stress-Induced Arterial Hypertension (ISIAH) rats simulating the stress-sensitive form of arterial hypertension. The work describes a genetic locus on chromosome 18, in which there are genes that control the development of cardiac hypertrophy associated with an increase in the concentration of norepinephrine in the hypothalamus, i.e., genes involved in enhanced sympathetic myocardial stimulation. No association of this locus with the blood pressure was found. Taking into consideration previously obtained results, it was concluded that the contribution to the development of heart hypertrophy in the ISIAH rats is controlled by different genetic loci, one of which is associated with the concentration of norepinephrine in the hypothalamus (on chromosome 18) and the other is associated with high blood pressure (on chromosome 1).

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