The replication of species A rotaviruses (RVAs) and other RNA viruses involves recruitment of and inter-action with the cellular organelles lipid droplets (LDs), both physically and functionally. Inhibition of en-zymes involved in the cellular fatty acid biosynthesis pathway or of cellular lipases that degrade LDs re-duces the functions of ‘viral factories’ (viroplasms for rotaviruses or replication compartments of other RNA viruses) and decreases the production of infectious progeny virus. Similarly, disturbance of the cellular lipid homeostasis in various ways blocks the replication of flaviviruses (hepatitis C viruses, Zikavirus, others), HIV-1, SARS-CoV-2, picornaviruses, noroviruses, influenza viruses and other negative-strand RNA viruses.

GPT-4 was released in March 2023 to wide acclaim, marking a very substantial improvement across the board over GPT-3.5 (OpenAI's previously best model, which had powered the initial release of ChatGPT). Despite the genuinely impressive improvement, however, there are good reasons to be highly skeptical of GPT-4's ability to reason. This position paper discusses the nature of reasoning; criticizes the current formulation of reasoning problems in the NLP community and the way in which the reasoning performance of LLMs is currently evaluated; introduces a collection of 21 diverse reasoning problems; and performs a detailed qualitative analysis of GPT-4's performance on these problems. Based on the results of this analysis, the paper argues that, despite the occasional flashes of analytical brilliance, GPT-4 at present is utterly incapable of reasoning.

Background: Hepatic erythrophagocytosis is augmented in NASH and amplifies inflammation and fibrosis. Although various pro-phagocytic signals have been identified on erythrocytes of NASH patients, the role of bound thrombospondin-1 (TSP-1), which acts as an “eat-me” signal, arginase-1, which regulates the levels of nitric oxide in erythrocytes, and phosphatidylethano-lamine (PE) which can amplify erythrophagocytosis and hepatic inflammation have not been explored. Hence, we sought to investigate the levels of arginase-1 and TSP-1 in erythrocyte lysate and PE in erythrocyte membranes of NASH patients. Methods: Twenty-four patients and 14 healthy controls participated in our study. The levels of TSP-1 and arginase were quantified by ELISA in erythrocyte lysates, and the levels of PE in erythrocyte membranes by thin layer chro-matography. Results: Erythrocytes of NAFLD patients exhibit lower levels of arginase-1 and TSP-1 (p<0.01). Erythrocyte-bound TSP-1 levels correlated with the levels of erythrocyte surface CD47. Phosphatidylethanolamine was increased in erythrocytes of NASH patients and was accompanied by increased release, indicating exposure. Conclusion: Our results imply reduced TSP-1 binding by erythrocytes which could allow free TSP-1 molecules to act on macrophages, enhancing erythrophagocytosis. Increased PE which could amplify inflammation after efferocytosis, while downregulation of arginase-1 could lead to defective efferocytosis.

In this work, nylon 6/ P(N-phenylmaleimide-alt-styrene) blends were prepared by melt blending, and the mechanical, heat-resistant, crystallographic and dynamical mechanical properties of nylon 6/ P(N-phenylmaleimide-alt-styrene) blends with different contents were investigated and analyzed. The results showed that the mechanical properties decreased with increasing PNS, while the heat deflection temperature (HDT), relative crystallinity (Xn), and storage modulus (G’) increased with increasing PNS. The results of differential Scanning Calorimetry (DSC) proved the PNS played the positive role of nucleating PA6. And the results of dynamic mechanical analysis (DMA) proved the PNS could improve the rigidity of PA6/PNS blends. From the SEM, these PNS domains were between 0.2 and 4 μm in diameter. The experimental results indicated that the addition of PNS improved the rigidity of PA6/PNS blends, and then improved the heat-resistant property.

The COVID-19 pandemic over the past years has shown a great need for rapid, low-cost and on-site detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this paper, an aptamer-based colloidal gold nanoparticle lateral flow test strip was well developed to realize the visual detection of wild type SARS-CoV-2 spike protein (SP) and multiple variants. Under the optimal reaction conditions, a low detection limit of SARS-CoV-2 S protein of 0.68 nM was acquired, and the actual detection recovery was 83.3% to 108.8% for real world samples. This suggests a potential tool for the prompt detection of SARS-CoV-2 with good sensitivity and accuracy, and a new method for the development of alternative antibody test strips for the detection of other viral targets.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation and regulate postprandial metabolism. These hormones are known as classical incretin hormones and are responsible for a major part of postprandial insulin release. The incretin effect is severely reduced in patients with type 2 diabetes, but it was discovered that administration of GLP-1 agonists was capable of normalizing glucose control in these patients. Over the last decades, much research has been focused on the development of incretin-based therapies for type 2 diabetes. These therapies include incretin receptor agonists and inhibitors of the incretin-degrading enzyme dipeptidyl peptidase-4. Especially the development of diverse GLP-1 receptor agonists has shown immense success, whereas studies of GIP monotherapy in patients with type 2 diabetes have consistently been disappointing. Interestingly, both GIP-GLP-1 co-agonists and GIP receptor antagonists administered in combination with GLP-1R agonists appear to be efficient with respect to both weight loss and control of diabetes, although the molecular mechanisms behind these effects remain unknown. This review describes our current knowledge of the two incretin hormones and the development of incretin-based therapies for treatment of type 2 diabetes.

Epidemiologic studies suggest an inverse correlation between coffee consumption and the occurrence of neurodegenerative diseases, but the role of caffeine and roasting degree are still matter of debate. The objective of this work was to evaluate the effects of caffeinated (light, medium, and dark roast) and decaffeinated instant coffee samples in acetylcholinesterase inhibition and antioxidant assays, as well as in animal models of Parkinson’s disease. Caffeinated coffees inhibited the acetylcholinesterase in much smaller concentrations than decaffeinated coffee. All coffee samples showed antioxidant capacity without relation with the caffeine content. Dopaminergic-like activity in the haloperidol-induced catalepsy test was observed with caffeinated coffee, but not in the decaffeinated sample. The medium roast coffee reduced the number of rotations of rats after methamphetamine administration on the 6-hydroxydopamine unilateral lesion of the medial forebrain bundle. However, the coffee treatment did not avoid the loss of dopaminergic neurons on substantia nigra pars compact and only the smallest dose of coffee was able to avoid the decrease of dopamine levels in the lesioned side of the striatum. Altogether, these results suggest that coffee exerts moderate pro-cholinergic and pro-dopaminergic effects and caffeine seems to be the main responsible for these effects.

Breakthrough curves for the adsorption of H2S using a metal-oxides mixture were predicted using the Bohart-Adams model of fixed bed adsorption. This mixture (ZnMn2O4+ZnO+Mn2O3) came from the processing of an urban waste as spent alkaline batteries were. The H2S adsorption experiments were carried out in a fixed-bed column at 20º C, and under various experimental conditions: gas flow rate, inlet H2S concentration and adsorbent dosage. Curves predicted by the model matched well with experimental data, providing data for the possible scale-up of the system. At the various experimental variables, the efficiency of the column, were also provided in the work. This investigation demonstrated the usefulness of a waste material, like spent alkaline batteries, to provide an adsorbent material to mitigate the problem of the presence of this harmful gas.

The PediCenter and Niles Children’s Clinic provide pediatric primary and urgent care services in central California. We remained open throughout the COVID-19 pandemic, providing scheduled well child-care and sick visits. Beginning in September 2020, we implemented a COVID-19 screening program. Screening was performed on all patients presenting for care and was made available to patients requiring testing for any purpose. Herein, we provide results from that program, including a description of clinical characteristics of COVID-19 in our patients. Key findings: 11,649 COVID-19 antigen screening tests were performed (age range 0.1 to 17.0, mean 8.7, SD 4.5). In total, 1,560 pts. (13.4%) tested positive. Among these, 665 (43%) were asymptomatic, 560 (36%) had mild disease, 318 (20%) had moderate disease, and 17 (1%) had severe disease. No critical cases or transfers to the emergency room were reported. Younger patient age was associated with an increased severity of illness, as was time from onset of pandemic. 4,446 patients reported no symptoms at the time of screening, 15% of whom tested positive. 7,203 patients reported symptoms at the time of testing. Among these, 87.6% tested negative and 12.4% tested positive. Disease severity was similar between these 2 groups. COVID-19 is generally a mild respiratory tract infection in healthy children. Screening is effective in identifying cases, including asymptomatic cases. Statistical models further revealed associations between patient age, time from the onset of the pandemic and disease severity.

Hydroperoxides (ROOH) are known as damaging agents capable of mediating mutation, while a role as signaling agents through oxidation of protein sulfhydryls that can alter cancer-related pathways has gained traction. Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme that reduces ROOH at the expense of glutathione (GSH). GPX2 is noted for a tendency of large in-creases or decreases in expression levels during tumorigenesis that leads to investigators focusing on its role in cancer. However, GPX2 is only one component of multiple enzyme families that metabolize ROOH and GPX2 levels are often very low in the context of these other ROOH reducing activities. Colorectal cancer (CRC) was selected as a case study for examining GPX2 function as colorectal tissues and cancers are sites where GPX2 is highly expressed. A case can be made for a significant impact of changes in expression levels. There is also a link between GPX2 and NADPH oxidase 1 (NOX1) from earlier studies that is seldom addressed and is discussed, presenting data on a unique association in colon and CRC. Tumor-derived cell lines are quite commonly used for pre-clinical studies involving the role of GPX2 in CRC. Generally, selection for this type of work is limited to identifying cell lines based on high and low GPX2 expression with the standard re-search scheme of overexpression in low expressing lines and suppression in high expressing lines to identify impacted pathways. This overlooks CRC subtypes among cell lines involving a wide range of gene expression profiles and a variety of driver mutation differences along with a large difference in GPX2 expression levels. A trend for low and high GPX2 expressing cell lines to segregate into different CRC subclasses, indicated in this report, suggests that choices based solely on GPX2 levels may provide misleading and conflicting results by disregarding other properties of cell lines and failing to factor in differences in potential protein targets of ROOH. CRC and cell line classification schemes are presented here that were intended to assist workers in performing pre-clinical studies but are largely unnoted in work on GPX2 and CRC. Studies are often initiated on the premise that the transition from normal to CRC is associated with up-regulation of GPX2. This is probably correct. However, the source normal cells for CRC could be almost any colon cell type, some with very high GPX2 levels. These factors are addressed in this study.

Introduction: A plethora of biological molecules regulate chondrogenesis in the epiphyseal growth plate. Disruptions of quantity and function of these molecules can manifest clinically as stature abnormalities of various etiologies. Traditionally, the growth hormone/insulin-like growth factor 1 (IGF1) axis represents the etiological center of final stature attainment. Of note, little is known about the molecular events that dominate the growth of the craniofacial complex and its correlation with somatic stature. Aim: Given the paucity of the relevant data, this review discusses available information regarding potential applications of lateral cephalometric radiography as a potential clinical indicator of genetic short stature in children. Materials and Methods: A literature search was conducted in the PubMed electronic database using the key words: cephalometric analysis and short stature; cephalometric analysis and achondroplasia; cephalometric analysis and hypochondroplasia; cephalometric analysis and skeletal abnormalities; cephalometr* and SHOX; cephalometr* and CNP; cephalometr* and ACAN; cephalometr* and CNVs; cephalometr* and IHH; cephalometr* and FGFR3; cephalometr* and Noonan syndrome; cephalometr* and “Turner syndrome”; cephalometr* and achondroplasia. Results: In individuals with genetic syndromes causing short stature, linear growth of the craniofacial complex is confined, following the pattern of somatic short stature regardless of its etiology. The angular cephalometric measurements differ from the average height normal individuals and are suggestive of a posterior placement of the jaws and a vertical growth pattern of the face. Conclusion: The greater part of the existing literature regarding cephalometric measurements in short statured children with genetic syndromes provides qualitative data. Furthermore, cephalometric data for individuals affected with specific rare genetic conditions causing short stature, should be the focus of future studies. These quantitative data are required to potentially establish cut-off values to refer for genetic testing based on craniofacial phenotypes.

Partial or transient cellular reprogramming is defined by the limited induction of pluripotency factors without fully de-differentiating cells into a pluripotent state. Comparing in vitro and in vivo mouse studies, and in vitro studies in humans, supported by visualizations of the interconnections among the data, we show consistent patterns in how such reprogramming modulates key biological processes. Generally, it leads to enhanced chromatin accessibility, upregulation of chromatin modifiers, and improved mitochondrial activity. These changes are accompanied by shifts in stress response programs, such as inflammation, autophagy, and cellular senescence, as well as dysregulation of extracellular matrix pathways. We also underscore the challenges in evaluating complex processes like aging and cellular senescence, given the variability in biomarkers used across studies. Overall, we highlight biological processes consistently influenced by reprogramming while noting that some effects are context-dependent, varying according to cell type, species, sex, and the reprogramming method employed. These insights inform future research and therapeutic applications in aging and regenerative medicine.

In the present study, we have systematically examined the clinical significance of Nectin-4 (encoded by the PVRL-4 gene), a marker for breast cancer stem cells (CSCs), in cancer metastasis and angiogenesis using a variety of human specimens, including invasive duct carcinoma (IDC) with multiple grades, several types of primary tumors to local and distant relapses, lymph node metastases and circulating tumor cells (CTCs). Nectin-4 was overexpressed in more than 92% of samples with 65.2% Nectin-4 positive cells. The level of expression was increased with increasing tumor grade (GI-III) and size (T1-4) of IDC specimens. More induction of Nectin-4 was noted in relapsed samples from a variety of tumors (colon, tongue, liver, kidney, ovary, buccal mucosa) in comparison to primary tumors, while paired adjacent normal tissues do not express any Nectin-4. A high expression of Nectin-4 along with other representative markers in CTCs and lymph node metastasis was also observed in cancer specimens. An increased level of Nectin-4 along with representative metastatic (CD-44, Sca1, ALDH1, Nanog) and angiogenic (Ang-I, Ang-II, VEGF) markers was noted in metastatic tumors (local and distant) in comparison to primary tumors that were correlated with different grades of tumor progression. In addition, greater expression of Nectin-4 was observed in secondary tumors (distant metastasis, e.g., breast to liver or stomach to gallbladder) in comparison to primary tumors. Nectin-4 was overexpressed at all stages of metastasis and angiogenesis, thus appearing to play a major role in tumor relapse through the PI3K-Akt-NFκβ pathway.

A single dose of psilocybin, a psychedelic and serotonin 2A receptor (5-HT2AR) agonist, may be associated with antidepressant effects. The mechanism behind its antidepressive action is unknown but could be linked to increased synaptogenesis and down-regulation of cerebral 5-HT2AR. Here, we investigate if a single psychedelic dose of psilocybin changes synaptic vesicle protein 2A (SV2A) and 5-HT2AR density in the pig brain. Twenty-four awake pigs received either 0.08 mg/kg psilocybin or saline intravenously. Twelve pigs (n=6/intervention) were euthanized one day post-injection, while the remaining twelve pigs were euthanized seven days post-injection (n=6/intervention). We performed autoradiography on hippocampus and prefrontal cortex (PFC) sections with [3H]UCB-J (SV2A), [3H]MDL100907 (5-HT2AR antagonist) and [3H]Cimbi-36 (5-HT2AR agonist). One day post psilocybin injection, we observed 4.4% higher hippocampal SV2A density and lowered hippocampal and PFC 5-HT2AR density (-15.21% to -50.19%). These differences were statistically significant in the hippocampus for all radioligands and in PFC for [3H]Cimbi-36 only. Seven days post-intervention, there was still significantly higher SV2A density in hippocampus (+9.24%) and PFC (+6.1%) whereas there were no longer any differences in 5-HT2AR density. Our findings suggest that psilocybin’s antidepressive actions are linked to increased persistent synaptogenesis and possibly also to an acute decrease in 5-HT2AR density.

Patients with predominantly antibody deficiencies (PAD) display hypogammaglobulinemia with a high prevalence of infections, along with autoimmune manifestations, benign and malignant lymphoproliferation and granulomatous disease. It is noteworthy that PAD patients, even those with defects in the same causative genes display a variable clinical phenotype, suggesting that additional genetic polymorphisms, located in either immune-related or non-immune-related genes, may affect their clinical and laboratory phenotype. In this context, we analyzed 80 PAD patients, including 70 with common variable immunodeficiency (CVID) for SERPINA1 defects, in order to investigate their possible contribution to PAD clinical phenotype. Eight CVID patients carried heterozygous pathogenic SERPINA1 defects with normal alpha-1 antitrypsin levels. Interestingly, the presence of the Z allele (rs28929474) which was found in three patients, was significantly associated with liver disease; hepatic complications were also observed in patients carrying the p.Leu23Gln (rs1379209512) and the p.Phe76del (rs775982338) alleles. Conversely, no correlation of SERPINA1 defective variants with respiratory complications was observed, although patients with pathogenic variants exhibit a reduced probability of developing autoimmune diseases. Therefore, we recommend SERPINA1 genetic analysis in PAD, in order to identify patients with a higher risk for liver disease.

The present article describes the synthesis of an isonicotinate-derived meso-arylporphyrin, that has been fully characterized by spectroscopic methods (including fluorescence spectroscopy), as well as by elemental analysis and by HR-MS. The structure of a n-hexane monosolvate has been determined by single crystal X-ray diffraction analysis. The radical scavenging activity of this new porphyrin against the 2,2-diphenyl-1-picrylhydrazyl (DDPH) radical has been measured. Its antifungal activity against three yeast strains (C. albicans ATCC 90028, C. glabrata ATCC 64677 and C. tropicalis ATCC 64677) has been tested, using the disk diffusion and the microdilution methods. Whereas the measured antioxidant activity was low, the porphyrin showed moderate but encouraging antifungal activity. Finally, a study of its effect on the germination of lentil seeds revealed interesting allelopathic properties.

The oral administration of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate, allows inducing a beneficial level of blood ketone bodies without the adverse effects due to the adhesion to a ketogenic diet. Several studies documented the therapeutic effectiveness of the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in treating neurodegenerative diseases as well as its boosting activity of athletic and cognitive performances during prolonged physical exercises. Further studies considering this ketone body ester for therapy of other pathologies are also underway. In the present work, we describe the synthesis of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate through the enantioselective transesterification of racemic ethyl 3-hydroxybutyrate with (R)-1,3-butanediol catalyzed by immobilized Candida antarctica lipase B (CAL-B). The enantiopure (R)-1,3-butanediol was in turn obtained from the kinetic resolution of the racemate by CAL-B catalyzed acetylation with vinyl acetate. The economy of the synthetic procedure has been improved by recycling the unreacted (S) enantiomers of the ethyl 3-hydroxybutyrate and 1,3-buatnediol after stereochemical inversion achieved by tosylation and SN2 with ammonium acetate. The overall procedure allows to incorporate up to 70% of the starting racemic reagents into the final product.

During HIV-1 virus assembly the genomic RNA (vRNA) is selected for packaging by the viral protein Gag because it contains a specific packaging signal, Psi. While there have been numerous studies of Gag-Psi interactions, there is almost no information on kinetic aspects of this interaction. We have investigated the kinetics of Gag binding to different RNAs using switchSENSE DRX2 technology. We measured the association rate of Gag binding to monomeric Psi, to a “Multiple Binding Site Mutant” Psi that is inactive for genome packaging in vivo, and to a scrambled Psi. We discovered that Gag binds more rapidly to Psi RNA than to the mutant or scrambled RNAs. Furthermore, rapid Gag association kinetics are retained within sub-regions of Psi: Gag associates more rapidly with RNA containing only the 3’ two of the three Psi stem-loops than with monomeric RNA containing the 5’ two stem-loops or a scrambled RNA. No differences were detectable with individual Psi stem-loops. Interestingly, the rate of binding of Gag molecules to Psi increases with increasing Gag concentration, suggesting cooperativity in binding. The results are consistent with the hypothesis that selectivity in packaging derives from kinetic differences in initiation of particle assembly.

The principal aim of this descriptive-survey investigation is to ascertain the factors influencing individuals' choice to purchase organic commodities in Tehran. The statistical populace for this examination comprised all patrons of food retail establishments in Tehran, with the sample size determined using the Cochran formula for an unknown community size, involving the distribution of 30 questionnaires to customers (n=439). Data collection was carried out through a random sampling technique. The survey instrument consisted of a questionnaire with two sections consisting of general queries (7 questions) and specific inquiries (23 items) categorized into four dimensions (product, price, place, and promotion) for the clientele. The questionnaire's validity was confirmed through face and content validation, while its reliability was assessed utilizing Cronbach’s alpha. Data analysis was conducted using SPSS25 software, encompassing both descriptive and inferential statistical analyses. The results revealed a positive and significant correlation between customers' inclination to consume organic goods and the characteristics of the product, price, and promotion. However, no association was found between the propensity to consume organic products and location characteristics. Concerning contextual variables, a solely positive and significant correlation was identified between the willingness to purchase organic items and consumer income levels. No significant relationships were detected between other contextual variables and organic product consumption. A notable contrast was observed between respondents' gender and their readiness to buy organic products, while no significant variances were noted regarding age, income, occupation, and education in relation to the propensity to purchase organic commodities.

With the fintech industry growing at an unprecedented rate, it is critical to protect cybersecurity and ensure data privacy. The research presented here offers a thorough examination of the challenges faced by financial technology companies, highlighting the growing risks posed by malware, phishing, and network vulnerabilities. As essential components of a proactive defense plan, the report promotes strong cybersecurity measures like frequent security assessments, encryption, and stringent access controls. The findings highlight how important it is for fintech companies to give cybersecurity equal importance with open and honest data privacy policies in order to win over customers. In order to protect the industry from cybersecurity risks regulatory compliance, intrusion detection systems, and collaborative information sharing are considered essential components. The article advises businesses to include cybersecurity and data privacy into their core business operations and customer relations, highlighting the critical role these factors play in sustaining success in the rapidly evolving fintech industry.

(1) Introduction: The COVID-19 pandemic presented unique challenges for patients and healthcare providers, especially for those working with obesity and related health problems. E-health has emerged as a crucial tool for the follow-up of users undergoing bariatric surgery during this period, allowing remote monitoring of users' health status and providing access to virtual consultation with health professionals. This study aims to analyze the impact of the use of telemedicine during the COVID-19 pandemic on the results of bariatric surgery and user satisfac-tion with this follow-up. (2) Method: Observational study with retrospective data collection. The variables were divided into several groups: health data, associated comorbidities, quality of life, quality of sleep and satisfaction with telemedicine monitoring. (3) Results: Surgery significantly affected weight loss, in general more than 75% loss of excess weight. Comorbidities, like the qual-ity of life, were reversed over time, with 50% of subjects maintaining excellent levels. Although most users were satisfied with the monitoring, the variables had no relationship. (4) Conclusions: The follow-up assured by telemedicine did not alter the results of bariatric surgery, which may allow us to infer that it may be an option to consider for regular monitoring of the post-bariatric surgery process.

Miscarriage due to blastocyst implantation failure occurs in up to two-thirds of all miscarriage cases in human. The calcium ion has been shown to be involved in many cellular signal transduction pathways as well as in the regulation of cell adhesion, which is necessary for the embryo implantation process. Exposure to endocrine-disrupting chemicals (EDs) during early gestation results in disruption of intrauterine implantation and uterine reception, leading to implantation failure. In this study, ovarian estrogen (E2), bisphenol A (BPA), or 4-tert-octylphenol (OP), with or without ICI 182,780 (ICI) were injected subcutaneously from gestation day 1 to gestation day 3 post-coitus. The expression levels of the calcium transport genes were assessed in maternal uteri and implantation sites. The number of implantation sites was significantly low in the OP group, and implantation sites were absent in the E2 and EDs+ICI groups. There were different calcium transient transport channel expression levels in uterus and implantation site samples. The levels of TRPV5 and TRPV6 gene expression were significantly increased by EDs with/without ICI treatment in uterus. Whereas, TRPV5 and TRPV6 gene expression were significantly lower in implantation sites samples. NCX1 and PMCA1 mRNA levels were significantly decreased by OP and BPA in the implantation site samples. Compared to vehicle treatment in uterus, both the MUC1 mRNA and protein levels were markedly high in all but the BPA group. Taken together, these results suggest that both BPA and OP can impair embryo implantation through alteration of calcium transport gene expressions and by affecting uterine receptivity.

Papillary thyroid carcinoma (PTC) presents a significant health concern, particularly among Hispanic women in the United States, who exhibit a disproportionately higher chance of developing an advanced disease when compared to the non-Hispanic population. Emerging evidence suggests coagulation factor X, encoded by F10 gene, has a potential role in inhibiting cancer cell migration. However, comprehensive investigations into the differential expression patterns of F10 in Hispanic versus non-Hispanic females remain limited. RNA-sequencing data was acquired from the TCGA database for white female patients, 166 non-Hispanic and 25 Hispanic. A statistically significant (p &lt; 0.05) 2.06-fold increase in F10 expression levels was detected in disease-free tumors compared to recurrent PTC tumors. Furthermore, an increase in F10 gene expression levels was also observed corresponding to approximately a 1.74-fold increase in non-Hispanic patients compared to Hispanic patients. The probability of tumor recurrence was 1.82 times higher in the cohort with low expression of F10 compared to the high expression cohort, correlating with the lower disease-free rates observed in Hispanic patients’ cohort when compared to non-Hispanics. This finding underscores the relevance of ethnic disparities in molecular profiles for understanding cancer susceptibility. Identifying F10 as a potential prognostic biomarker highlights avenues for targeted interventions and contributes to improving diagnostic and treatment strategies for diverse patient populations.

The analysis of particulate matter (PM) in dilute solutions is an important target for environmental, geochemical and biochemical researches. Here we show how the microdrop technology may allow to control, through the evaporation of small droplets, the deposition of insoluble materials dispersed in a solution on a well-defined area with a specific spatial pattern. Using this technology the superficial density of the deposited solute can be accurately controlled. In particular, it becomes possible to deposit an extremely reduced amount of insoluble material -in the order of few μg- on a confined area, thus allowing a relatively high superficial density to be reached within a limited time. In this work we quantitatively compare the microdrop technique for the preparation of particulate matter samples with the classical filtering technique. After having been optimized, the microdrop technique allows to obtain a more homogeneous deposition and limit sample consumption of a factor ~25. This method is potentially suitable for many novel applications in different scientific fields.

Chronic inflammation alters lipoprotein metabolism and causes changes in serum concentrations of lipids, C-reactive protein (CRP), and paraoxonase-1 activity (PON-1), an enzyme, which in the gastrointestinal tract may act as a local detoxifier, antioxidant, and immunomodulator. However, unlike in people with inflammatory bowel disease, scarce information is available in dogs with protein-losing enteropathy secondary to chronic inflammatory enteropathy (iPLE). The first aim was to describe and compare the lipid profile, CRP concentrations and PON-1 activity in healthy dogs and in dogs with iPLE. The second aim was to evaluate correlations among clinicopathological, histologic data, and lipid profiles in dogs with iPLE. Serum samples from 51 iPLE and 40 healthy dogs were used to study albumin, total protein, CRP, PON-1 activity, cholesterol, triglycerides, and lipoprotein classes obtained by electrophoretic separation. There was a significant difference of all serum analytes between iPLE and healthy dogs. Significant correlations between the lipid profile and the existing chronic enteropathy activity index were not found. Some lipoprotein classes correlated with CRP and PON-1. Triglycerides were significantly higher in dogs with both inflammation and lymphangiectasia. Lipoproteins, CRP and PON-1 activity are altered in dogs with iPLE. Results need to be confirmed in further studies.

Chronic Myeloid Leukemia (CML) is one of the most commonly found types of myeloproliferative neoplasms, characterized by increased proliferation of granulocytic cells without losing their differentiation ability. Imatinib, a Tyrosine Kinase Inhibitor (TKI), can be effectively used as therapy for CML. However, imatinib can affect bone turnover, thus having clinical implications on the bones of CML patients undergoing long-term imatinib therapy. However, parameters that can accurately describe the bone condition in CML patients receiving imatinib still need further study. A combination of imaging techniques such as Bone Mineral Density (BMD) and bone turnover activity markers such as C-terminal telopeptide of type I collagen (CTX-1) and Osteocalcin has the potential to be used as monitoring parameters for bone density abnormalities in CML patients receiving imatinib. This article explains the rationale for using BMD, CTX-1, and Osteocalcin as monitoring parameters of bone remodeling in CML patients receiving imatinib. First, the physiological process of bone turnover will be explained. Then, we describe the role of tyrosine kinase in bone metabolism. Next, the impact of imatinib on BMD, CTX-1, and Osteocalcin will be explained. In conclusion, the assessment of bone health of CML patients on Imatinib should include both BMD tests and bone turnover marker assays such as CTX-1 and Osteocalcin.

In the frame of our diversity-oriented research on multitarget small molecule anticancer agents, utilizing convergent synthetic sequences terminated by Sonogashira coupling reactions, a preliminary selection of representative alkyne-tethered vindoline hybrids was synthesized. The novel hybrids with additional pharmacophoric fragments of well-documented anticancer agents, including FDA-approved tyrosine-kinase inhibitors (imatinib and erlotinib) or ferrocene or chalcone units, were evaluated for their antiproliferative activity on malignant cell lines MDA-MB-231 (triple negative breast cancer), A2780 (ovarian cancer), HeLa (human cervical cancer) and SH-SY5Y (neuroblastoma) as well as human embryonal lung fibroblast MRC-5 served as reference non-malignant cell line for the assessment of the therapeutic window of the tested hybrids. The biological assays identified a trimethoxyphenyl-containing chalcone-vindoline hybrid (36) as a promising lead compound exhibiting submicromolar activity on A2780 cells with a marked therapeutic window. These results suggest that ovarian cancer might be considered as a prioritized target of treatment with 36.

This paper considers a new approach to the modeling of the vacuum infusion process at the manufacturing three-dimensional composite parts of complex shape. The developed approach and numerical methods are focused on the reliable prediction with the needed accuracy and elimination the unrecoverable defect of composite structure such as the dry spots. The paper presents some experimental results, which demonstrate two cases of dry spots formation in large aircraft composite panels, and analyses the reasons of these defects arising. Our numerical technique is based on the vacuum infusion of the liquid resin into porous preform as the two phase flow, which is described by the phase field equation coupled with the Richards equation describing the fluid motion in unsaturated soils with spatially varied pressure dependant porosity and saturation. This problem statement allowed to correctly reconstruct the resin front motion and formation of inner and outer dry spots depending on its movement. For the rapid detection of preform zones that are suspicious for defect formation two indicators calculated during process simulation are proposed and tested at the numerical experiments. The auxiliary program tool has been developed in MATLAB environment to correctly detect the times of formation, localization and dimensions of the arising dry spots by using the results of the finite element model simulation.

The blood–brain barrier (BBB) plays pivotal roles in synaptic and neuronal functioning by sealing the space between adjacent microvascular endothelial cells. BBB breakdown is present in patients with mild cognitive impairment (MCI) or Alzheimer disease (AD). Claudin-5 (CLDN-5) is a tetra-spanning protein essential for sealing the intercellular space between adjacent endothelial cells in the BBB. In this study, we developed a blood-based assay for CLDN-5 and investigated its diagnostic utility by using 100 cognitively normal (control) subjects, 100 patients with MCI, and 100 patients with AD. Plasma CLDN-5 levels were increased in patients with AD (3.08 ng/mL) compared with controls (2.77 ng/mL). Plasma levels of phosphorylated tau (pTau181), a biomarker of pathological tau, were elevated in patients with MCI or AD (2.86 and 4.20 pg/mL, respectively) compared with control subjects (1.81 pg/mL). In patients with MCI or AD, plasma levels of CLDN-5—but not pTau181—decreased with age, suggesting some age-dependent BBB changes in MCI and AD. These findings suggest that plasma CLDN-5 may a potential biochemical marker for the diagnosis of MCI and AD.

Bacillus Calmette-Guérin (BCG) therapy for patients with non-muscle invasive bladder cancer (NMIBC) faces limitations in efficacy and significant side effects, aggravated by a recent global shortage. In this prospective clinical study, we report outcomes of sequential intravesical adminis-tration of gemcitabine and docetaxel (Gem/Doce) as the first-line treatment in BCG-naïve patients with high-risk NMIBC (HR NMIBC). From October 2019 until April 2022, we enrolled 52 patients and followed treatment protocol set by the University of Iowa. Follow-up assessments were con-ducted every 3 months. In this cohort, 25 (48.1%) patients were diagnosed with T1HG bladder cancer, 10 (19.2%) patients had carcinoma in situ (CIS), and 17 (32.7%) patients had a combination of CIS+T1HG. Median time to first recurrence in T1HG, CIS and T1HG+CIS groups was 11, 10.5 and 8.8 months, respectively. The recurrence-free survival was 98.1%, 94.2% and 80.8% at 6, 9 and 12 months, respectively. The rate of progression-free survival was 100%, 98.1% and 92.3% at 6, 9 and 12 months, respectively. We demonstrated the safety and efficacy of Gem/Doce therapy in BCG-naïve patients with HR NMIBC during a one-year follow-up. Further research with extended follow-up, as well as direct comparison of Gem/Doce and other anticancer agents, are essential.

We construct a Bayesian estimator for the dilution of a wastewater sample. When wastewater is diluted by rainwater an estimate of the level of dilution is required if we are to normalise sample measurements of disease markers such as SARS-CoV-2 RNA. We consider the situation where flow measurements are available, but will regularly be unreliable because of the action of combined sewer outflows (CSOs) and wastewater storage tanks, which divert wastewater away from treatment plants when the flow is excessive. However, we also have proxies for the flow from various chemical markers (e.g.\ phosphate, ammonium, electrical conductivity), whose level per unit of population is fixed. The new flow estimator has multiple advantages compared to existing procedures: credible intervals for the estimates; optimal weighting of the chemical markers; systematic handling of missing and censored values; and model based smoothing without lags.

The development of novel coherent and brilliant sources, such as soft X-ray Free Electron Laser (FEL) and High Harmonic Generation (HHG) enables new ultrafast analysis of the electronic and structural dynamics of a wide variety of materials. Soft X-ray FEL delivers high brilliance beams with short pulse duration, high spatial coherence and photon energy tunability. In com-parison with FELs, HHG X-ray sources are characterized by a wide spectral bandwidth and few to sub-femtosecond pulses. The approach will lead to time-resolved reconstruction of molecular dynamics, shedding light on different photochemical pathways. The high peak brilliance of soft X-ray FELs facilitates investigations in nonlinear regime, while the broader spectral bandwidth of the HHG sources may provide the simultaneous probing of multiple components. Significant technical breakthroughs in these novel sources are under way to improve brilliance, pulse dura-tion, and to control spectral bandwidth, spot size, and energy resolution. Therefore, in the next few years, the new generation of soft X-ray sources combined with novel experimental tech-niques, new detectors, and computing capabilities will allow the study of several extremely-fast dynamics, such as vibronic dynamics. In the present review, we shortly discuss recent devel-opments in experiments, performed with soft X-ray FELs and HHG sources, operating near car-bon K-absorption edge, being a key atomic component in biosystems and soft materials. Differ-ent spectroscopy methods such as time-resolved pump-probe techniques, nonlinear spectrosco-pies and photoelectron spectroscopy studies have been addressed in an attempt of a better un-derstanding of fundamental physico-chemical processes

Information on the detection of the presence and potential for degradation of synthetic polymers (SPs) under various environmental conditions is of increasing interest and concern to a wide range of specialists. At this stage, there is a need to understand the relationship between the main par-ticipants in the processes of (bio)degradation of SPs in various ecosystems (reservoirs with fresh and sea water, soils, etc.), namely the polymers themselves, the cells of microorganisms (MOs) partici-pating in their degradation, and humic substances (HSs), which constitute a macrocomponent of natural non-living organic matter of aquatic and soil ecosystems, formed and transformed in the processes of mineralization of bioorganic substances in environmental conditions. Analysis of the main mechanisms of their influence on each other and the effects produced that accelerate or inhibit polymer degradation can create the basis for scientifically based approaches to the most effective solution to the problem of degradation of SPs, including in the form of microplastics. This review is aimed at comparing various aspects of interactions of SPs, MOs and HSs in laboratory experiments (in vitro) and environmental investigations (in situ) aimed at the biodegradation of polymers, as well as pollutants (antibiotics and pesticides) that they absorb. Comparative calculations of deg-radation velocity of different SPs in different environments are presented. A special place in the analysis is given to the elemental chemical composition of HSs, which are most successfully in-volved in the biodegradation of SPs. In addition, the role of photooxidation and photoaging of polymers under the influence of the ultraviolet spectrum of solar radiation under environmental conditions on the (bio)degradation of SPs in the presence of HSs is discussed.

Smith-Magenis syndrome is a complex neurobehavioral genetic disorder. The spectrum of SMS phenotype is broad but commonly includes craniofacial, neurobehavioral, and otolaryngologic features. While the etiology of SMS is commonly attributed to one copy interstitial deletion in the 17p11.2 region (90-95% of cases), variants identified by sequence analysis in RAI1 have also been reported in 5-10% of cases. The phenotypic spectrum of patients with RAI1 sequence alterations is not clear. In this study, we report a 9-year-old male with global cognitive and psychomotor developmental delay, musculoskeletal and cardiovascular abnormalities, and dysmorphic craniofacial features. Whole genome quad analysis of the proband, unaffected parent, and unaffected brother identified a novel de novo RAI1:c.2736delC variant. This is the first report of this variant in the literature. This report also highlights the details of the genome analysis and this patient's phenotypic spectrum.

Fatigue and dyspnea are the most commonly presented long-term complaints in individuals previously infected with SARS-CoV-2. The purpose of the study was to comprehensively evaluate diaphragm muscle function in COVID-19 survivors, as well as investigate whether potential diaphragm dysfunction will contribute to physical functioning impairment. 46 patients qualified to pulmonary rehabilitation were examined. Diaphragm muscle function parameters were evaluated using ultrasonography, while severity of dyspnea, aerobic capacity and amount of energy used by the body during physical activity were assessed by 6-minute walk test, mMRC scale and Metabolic Equivalent Task (MET), respectively. We identified 69.5% patients with diaphragm atrophy and 6.5% with diaphragm paralysis. Percentage of atrophy was not related to age, gender, BMI index, oxygen therapy use during COVID-19 infection course and severity of disease. Patients with presence of cough, fever and without loss of smell during COVID-19 course had a significantly greater values of diaphragm inspiratory thickness, while patients with cough and no smell disorders had a significantly lower percentage of diaphragm atrophy. Diaphragm functional parameters were strongly associated with selected variables of person's exercise tolerance, such as distance in 6-minute walk test, saturation level, fatigue and exertion in Borg scale. In conclusion, diaphragm muscle dysfunction is a serious long-term post-COVID aftermath and can be viewed as a major contributing factor of prolonged functional impairments.

The aim of this study was to investigate the relationship between postprandial glycemic levels based on flash-monitoring and the production of intestinal hydrogen (H2) and methane (CH4) gases based on measurement of the amount of these gases in exhaled air. We studied 14 subjects with type 2 diabetes mellitus (T2DM) and 10 individuals without diabetes (control) with 3 food-load tests with simultaneous determination of gases in exhaled air and assessment of glucose levels. In 15.4% of patients with T2DM, there was a non-significant increase in exhaled H2. How-ever, all subjects in the control group had significant increase in exhaled H2. Moreover, the level of H2 in exhaled breathafter food load in patients with T2DM was lower than in normoglycemic subjects. Also, in normoglycemic subjects there was an inverse correlation between maximum glucose rise and maximum H2 in exhaled air after food load. At the same time in patients with T2DM the level of CH4 in exhaled air directly correlated with the parameters of postprandial glycemia in the test with lactulose. Confirmation of a causal relationship between decreased H2 production, increased intestinal CH4 production, and more severe postprandial glycemia may identify new therapeutic targets in the correction of postprandial glycemia in patients with T2DM.

We describe a selective and sensitive fluorescence platform for the detection of trinitrophenol (TNP) based on competitive host–guest recognition between pyridine-functionalized pillar[6]arene (PCP6) and probe (acridine orange, AO) that used PCP6-functionalized reduced graphene (PCP6-rGO) as the receptor. TNP is an electron-deficient and negative molecule which is captured by PCP6 via electrostatic interactions and π-π interactions. Therefore, a selective and sensitive fluorescence sensor for TNP detection is developed. It has a low detection limit of 0.0035 μM (S/N=3) and a wider linear response of 0.01−5.0 and 5.0−125.0 for TNP. The sensing platform is also used to test TNP in two water and soil samples with satisfying results. This suggests that this approach has potential applications for the determination of TNP.

Copper (Cu) is a critical element for cancer cell proliferation and considerably accumulates in the nucleus. 64Cu2+ is an anticancer radiopharmaceuticals targeting the copper requirement of cancer cells. However, intravenously injected 64Cu2+ ions primarily accumulate in the liver. Ligand complexation of 64Cu2+ would be a promising method for increasing tumor delivery by reducing liver uptake. Herein, we used three tripodal amine ligands [tris(2-aminoethyl)amine (Tren), diethylenetriamine (Dien), and tris(2-pyridylmethyl)amine (TPMA)] to enclose 64Cu2+ ions and compared their in vivo tumor and liver uptake using a tumor-bearing xenograft mouse model of the extrahepatic bile duct carcinoma cell line TFK-1. We examined intracellular Cu distribution using microparticle-induced X-ray emission (micro-PIXE) analysis for these compounds. 64Cu2+-Tren and 64Cu2+-Dien showed higher tumor uptake than 64Cu2+-TPMA and 64Cu2+ ions in TFK-1 tumors. Among the three 64Cu2+ complexes and 64Cu2+ ions, liver uptake was inversely correlated with tumor uptake. Micro-PIXE analysis showed that in vitro cellular uptake was similar to in vivo tumor uptake and nuclear delivery was the highest for 64Cu2+-Tren. Conclusively, an inverse correlation between tumor and liver uptake was observed using three 64Cu2+ complexes of tripodal amine ligands and 64Cu2+ ions. These results provide useful information for the future development of anticancer 64Cu radiopharmaceuticals.

A phase 1-2, prospective, multicenter, randomized, open-label clinical trial (Code RPCEC00000382, https://rpcec.sld.cu/trials/RPCEC00000382-En/), with parallel groups, involving 1161 participants was designed to assess safety and immunogenicity of two Cuban COVID-19 vaccines (Mambisa and Abdala) in boosting COVID-19 immunity of convalescent adults after receiving one dose of either vaccine. The main safety outcome was severe vaccination adverse events occurring in &lt;5% of vaccinees. Main immunogenicity success endpoints were ≥4-fold anti-RBD IgG seroconversion or ≥20% increase in ACE2-RBD inhibitory antibodies in &gt;55% of vaccinees in Phase 1 and &gt;70% in Phase 2. Neutralizing antibody titers against SARS-CoV-2 variants were evaluated. Both vaccines were safe; no deaths or severe adverse events occurred. Mild intensity adverse events were the most frequent (&gt;73%); headache predominated for both vaccines. Phase 1 responders were 83.3% (p = 0.0018) for Abdala. Mambisa showed similar results. Phase 2 responders were 88.6% for Abdala (p &lt;0.0001) and 74.2% for Mambisa (p = 0.0412). In both phases, anti-RBD IgG titers, inhibition percentages and neutralizing antibody titers increased significantly after the booster dose. Both vaccines were safe and their immunogenicity surpassed the study endpoints.

Abstract Background: Occipital neuralgia is a debilitating condition and traditional treatments often provide limited or temporary relief. Recently, ultrasound-guided hydrodissection of the greater occipital nerve (GON) has emerged as a promising minimally invasive approach. Objectives: To describe two novel ultrasound-guided hydrodissection with 5% dextrose for GON and discuss their advantages, disadvantages, and considerations. Methods: Two case reports are presented. Case 1 describes a lateral decubitus approach for hydrodissecting the GON between the semispinalis capitis (SSC) and obliquus capitis inferior (OCI) muscles. Case 2 details a cranial-to-caudal approach for hydrodissecting the GON within the SSC and upper trapezius (UT) muscles when the GON pass through these two muscles. Results: Both patients experienced significant and sustained pain relief with improvements in function and quality of life. Conclusions: Ultrasound-guided GON hydrodissection using 5% dextrose is a promising treatment for occipital neuralgia. The lateral decubitus and cranial to caudal approaches provide additional options to address patient-specific anatomical considerations and preferences.

Mutations in KRT1 (keratin 1) or KRT10 (keratin 10) underlie a spectrum of diseases known as keratinopathic ichthyoses. Epidermolytic ichthyosis (EI) is caused by heterozygous missense mutations in the genes KRT1 or KRT10, mutations in the gene KRT2 (keratin 2) lead to superficial epidermolytic ichthyosis, and congenital reticular ichthyosiform erythroderma is caused by frameshift mutations in the genes KRT10 or KRT1, which lead to the phenomenon of revertant mosaicism. Epidermolytic ichthyosis is also present in a mosaic pattern known as epidermolytic (acantholytic) nevus, isolated or diffuse. In the latter case, gonadic involvement is possible, leading to a rare pedigree in which a parent with diffuse epidermolytic nevus (linear EI) gives birth to a child affected by EI. We present here an update on the phenotypic presentations of keratinopathic ichthyoses and their molecular mechanisms.

To characterize the mechanisms by which the highly-conserved exocyst trafficking complex regulates eye physiology in zebrafish and mice, we focused on exoc5 (aka sec10), a central exocyst component. We analyzed both exoc5 zebrafish mutants and retinal pigmented epithelium (RPE)-specific Exoc5 knockout mice. Exoc5 is present in both the non-pigmented epithelium of the ciliary body and in the RPE. In this study we set out to establish an animal model to study the mechanisms underlying the ocular phenotype and to establish if loss of visual function is induced by postnatal RPE Exoc5-deficiency. Exoc5-/- zebrafish showed smaller eyes, with decreased number of melanocytes in the RPE and shorter photoreceptor outer segments. At 3.5 days post fertilization, loss of rod and cone opsins were observed in zebrafish Tg:exoc5 mutants. Mice with postnatal RPE-specific loss of Exoc5 showed retinal thinning associated with compromised visual function, and loss of visual photoreceptor pigments. This retinal phenotype in Exoc5-/- mice was present at 20-weeks, and the phenotype was more severe at 27-weeks, indicating progressive disease phenotype. We previously showed that the exocyst is necessary for photoreceptor ciliogenesis and retinal development. Here, we report that exoc5 mutant zebrafish and mice with RPE-specific genetic ablation of Exoc5 develop abnormal RPE pigmentation, resulting in retinal cell dystrophy and loss of visual pigments associated with compromised vision. As RPE cells are “downstream” of photoreceptor cells in the visual process, these data suggest exocyst-mediated retrograde communication and dependence between the RPE and photoreceptors.

Colorectal cancer is one of the most common causes of cancer mortality worldwide, and innovative drugs for the treatment of colorectal cancer are continually being revealed. 5-Fluorouracil (5-FU) is a common clinical chemotherapeutic drug. Acquired resistance to 5-FU is a clinical challenge in colorectal cancer. Parecoxib is a selective COX-2-specific inhibitor, which has been demonstrated to inhibit metastasis in colorectal cancers in our previous study. This study aimed to investigate the synergistic antimetastatic activities of parecoxib to 5-FU in human colorectal cancer cells and determine the underlying mechanism. parecoxib and 5-FU synergistically suppressed metastasis in colorectal cancer cells. Treatment with the parecoxib /5-FU combination induced an increase in E-cadherin and decrease in β-catenin. The parecoxib/5-FU combination could inhibit MMP-9 and MMP-2 expression and MMP-9 activity, and the NF-κB pathway might be suppressed as well. Mechanistic analysis denoted that the parecoxib/5-FU combination hindered the essential molecules of the PI3K/Akt route to obstruct metastatic colorectal cancer. Furthermore, the parecoxib/5-FU combination could inhibit reactive oxygen species. Our work showed the antimetastatic capacity of the parecoxib/5-FU combination for colorectal cancers via targeting the PI3K/Akt /NF-κB pathway.

Exposure to psychosocial stress is a risk factor for cardiovascular disease, including vascular aging, angiogenesis, and atherosclerosis-based cardiovascular disease (ACVD). Dipeptidyl peptidase-4 (DPP-4) is a complex enzyme (also called CD26) that acts as a membrane-anchored cell surface exopeptidase. DPP4 is upregulated in metabolic and inflammatory cardiovascular disorders. The widespread expression of DPP4 macrophages and immune cells and the noncatalytic function of DPP4 (also called CD26) as a signaling and binding protein across a wide range of species suggest a teleological role for DPP4 in inflammation and immune response. DPP-4 exhibits many physiological and pharmacological functions by regulating its extremely abundant substrates [e.g., stromal cell-derived factor-1α/ C-X-C chemokine receptor type-4, glucagon-like peptide-1 (GLP-1), etc.]. Over last ten year, emerging data demonstrated unexpected roles for GLP-1 and DPP-4 in extracellular and intracellular signaling, immune activation, inflammation, oxidative stress production, cell apoptosis, insulin resistance, and lipid metabolism,. This mini review has focuses on recent novel findings in this field, highlighting an imbalance between GLP-1 and DPP4 as a potential therapeutic molecular target in treatments of chronic psychological stress-related atherosclerotic cardiovascular disease in humans and animals.

The BRAFV600E mutation, found in approximately 50% of melanoma cases, is associated with aggressive tumor behavior and poor prognosis. This study aimed to assess its impact on immunogenic cell death (ICD), a pivotal cytotoxic process triggering anti-tumor immune responses. Through comprehensive in silico analysis of The Cancer Genome Atlas data, we explored the association between the BRAFV600E mutation, immune subtype dynamics, and tumor mutation burden (TMB). Our findings revealed that the mutation correlated with a lower TMB, indicating a reduced generation of immunogenic neoantigens. Investigation into immune subtypes reveals an exacerbation of immunosuppression mechanisms in BRAFV600E-mutated tumors. To assess the response to ICD inducers, including doxorubicin and Me-ALA-based photodynamic therapy (PDT), compared to the non-ICD inducer cisplatin, we used distinct melanoma cell lines with wild-type BRAF (SK-MEL-2) and BRAFV600E mutation (SK-MEL-28, A375). We demonstrated a differential response to PDT between the WT and BRAFV600E cell lines. Further transcriptomic analysis revealed upregulation of IFNAR1, IFNAR2, and CXCL10 genes associated with the BRAFV600E mutation, suggesting their involvement in ICD. Using a gene reporter assay, we showed that PDT robustly activated the IFN-1 pathway through cGAS-STING signaling. Collectively, our results underscore the complex interplay between the BRAFV600E mutation and immune responses, emphasizing a putative correlation between tumors carrying the mutation and their responsiveness to therapies inducing the IFN-1 pathway, such as the ICD inducer PDT, possibly mediated by the elevated expression of IFNAR1/2 receptors.

The Flack Parameter is now almost universally reported for all chiral materials characterized by X-ray crystallography. It’s elegantly simplicity was an inspired development by Flack, and although the original algorithm for its computation has been strengthened by other workers, it remains an essential outcome for any crystallographic structure determination. As with any one-parameter metric, it needs to be interpreted in the context of its standard uncertainty.

The combustion of PVC cables in fires results in the release of hydrogen chloride gas. In the European Union, Regulation (EU) No 305/2011, in force since 2017, requires the classification of cables permanently installed in buildings for reaction to fire, smoke, flaming droplets, and acidity. The additional classification for acidity is evaluated through EN 60754-2, involving pH and conductivity measurements. This study focuses on the essential research and development of low-smoke acidity PVC compounds for cables, mainly aiming to meet the stringent additional classifications for acidity, a1 or a2, which cannot be achieved with traditional PVC cables. Understanding the chemistry of thermal decomposition and combustion, especially in the presence of hydrogen chloride scavengers, is crucial for meeting the best acidity classification. The article reviews the current tube furnace tests used in the European Union for cable halogen and acidity assessments. It discusses the limitations of the existing method (EN 60754-2) and highlights the potential of emerging tests such as IEC EN 60754-3, which employs ion chromatography for improved sensitivity and specificity. In the experimental part of the article, various standard and low-smoke acidity cable compounds are tested using tube furnace experiments with different heating regimes. The concentrations of cations and anions in solution are measured through ion chromatography and inductively coupled plasma–optical emission spectrometry. This detailed analysis aims to identify the species influencing pH and conductivity, which is crucial for designing effective acid scavengers that do not impact conductivity. The conclusive results emphasize that HCl from PVC thermal decomposition is the primary driver of pH and conductivity, and the contribution from the decomposition of additives and byproducts from combustion is found to be negligible in most of the tested PVC compounds for cables. The findings underscore the importance of understanding the thermal decomposition of PVC compounds to design acid scavengers capable of trapping hydrogen chloride without adversely impacting conductivity.

Long COVID, a name often given to the persistent symptoms following acute SARS-CoV-2 infection, poses a multifaceted challenge for health. This review explores the intrinsic relationship between comorbidities and autoimmune responses in shaping the trajectory of long COVID. Autoantibodies have emerged as significant players in COVID-19 pathophysiology, with implications for disease severity and progression. Studies show immune dysregulation persisting months after infection, marked by activated innate immune cells and high cytokine levels. The presence of autoantibodies against various autoantigens suggests their potential as comorbid factors in long COVID. Additionally, the formation of immune complexes may lead to severe disease progression, highlighting the urgency for early detection and intervention. Furthermore, long COVID is highly linked to cardiovascular complications and neurological symptoms, posing challenges in diagnosis and management. Multidisciplinary approaches, including vaccination, tailored rehabilitation, and pharmacological interventions, are used for mitigating long COVID's burden. However, numerous challenges persist, from evolving diagnostic criteria to addressing the psychosocial impact and predicting disease outcomes. Leveraging AI-based applications holds promise in enhancing patient management and improving our understanding of long COVID. As research continues to unfold, unravelling the complexities of long COVID remains paramount for effective intervention and patient care.

Real time camouflaged object detection so far using CAMO or COD10K datset has been able to achieve mAP50 less than 64%. We present a fourier transfom and Milkyway filament extraction based method extracting shape and edges of camouflaged object, achieving 88%+ mAP50 while continuing to deliver real time detection using YOLOv8s based models. This allows for search and rescue of wilelife and humans in smoke, fog, natural disasters possible by combining low compute Yolov8s model on headup display for rescue workers such as firefighters, first reponders etc.

Hip joint surgeries, including total hip replacement or resurfacing, have increased tremendously in the last decades. Number of patients of all ages, replace their hip, due to severe injuries or trauma problems, so as to have a better life. According to these factors, new material and processes in implants manufacturing are imported to medicine, through research programs, every year. In the scope of one of these programs, that has to do with ceramic coatings on metallic resurfacing implants, a new 3axis Hip simulator was designed and manufactured in the Laboratory of Manufacturing Technology of the National Technical University of Athens. The scope of this paper is to present the main parts, materials and process used to manufacture the simulator as well as the way the simulator is working and how its movement in 3axis is accomplished. Furthermore, the evaluation of the machine and its use to examine resurfacing implants is presented.

Isoamyl (E)-3-(3,4-dimethoxyphenyl)acrylate (1) was obtained 95% yield by 2-methyl-6-nitrobenzoic anhydride (MNBA)/4-dimethylaminopyridine (DMAP)-catalyzed reaction at room temperature for 190 minutes in dichloromethane. The structure of isoamyl (E)-3-(3,4-dimethoxyphenyl)acrylate (1) was established by NMR, FTIR, and the high resolution of mass spectroscopies. In vitro sun protection factor evaluation exhibited value of 37.10 ± 0.03 which indicates that isoamyl (E)-3-(3,4-dimethoxyphenyl)acrylate (1) as a sunscreen agent with high protection.

A statistical simulation is presented which reproduces the correlation obtained from EPR coincidence experiments without non-local connectivity. Defining spin under the quaternion group reveals hyper-helicity, a hitherto missed attribute of spin. Including this in the treatment, reveals two complementary properties: spin polarization and spin coherence. The former has a CHSH value of 2, and spin coherence has a CHSH = 1 giving CHSH = 3 for an EPR pair. The simulation here gives 2.995. We suggest that Nature has CHSH=3 being considerable more than predicted from quantum mechanics of $2\sqrt{2}$. There are no Local Hidden Variables. We suggest that quaternion spin is more fundamental than Dirac spin. A computer program which performs the simulation without non-local connectivity is described.

Network Simulators (NS) is typically used to study services and applications in complex scenarios due to the infeasibility of deploying real testbeds. This is the case of Mobile Ad hoc Networks (MANETs) which can be extensively used in emergency situations or to gather information without infraestructure. An important factor to get realiable results in the MANETs’ simulations is the wireless channel module of NSs. In this report, we explain how thw wireless channel is implemented in NS-3 and it can be configured.

A new bisthiourea compound, 1,3,1',3'-(dinaphthalene-1,8-diyl)bisthiourea, was synthesized. Its structure was characterized by elemental analysis, FT-IR and 1H-, 13C-NMR and MS spectroscopic techniques.

Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of regulation of efficient virus replication. In this study, we comprehen-sively addressed the deregulation of host miRNAs by massive-parallel sequencing. We found that only miRNAs expressed from a single cluster, miR-183/96/182 are reproducibly deregulated dur-ing productive infection. These miRNAs are predicted to regulate a great number of potential tar-gets involved in different cellular processes and have only 33 shared targets. Among these, mem-bers of the FoxO family of proteins were identified as potential targets for all three miRNAs. However, our study shows that the upregulated miRNAs do not affect the expression of FoxO proteins, moreover these proteins were upregulated in HSV-1 infection. Furthermore, we show that the individual FoxO proteins are not required for efficient HSV-1 replication. Taken together, our results indicate a complex and redundant response of infected cells to the virus infection that is efficiently inhibited by the virus.

Omicron SARS-CoV-2 variants have dominated the strains of COVID-19 circulating worldwide for the last two years. Although the mortality rate of the COVID-19 Omicron variants is only approximately half that of previous variants, vaccines effective against Omicron are needed. Demonstrating that a SARS-CoV-2 vaccine can protect against Omicron in an in vivo infection model, particularly in that of Syrian hamsters, is important for the preclinical characterization of SARS-CoV-2 vaccines. Here, we report on the evaluation of W-PreS-O for its ability to protect Syrian hamsters against infection by Omicron. W-PreS-O is a chimeric vaccine based on a single fusion protein (W-PreS-O), combining RBDs from Wuhan hu-1 wild-type and Omicron adsorbed to aluminum hydroxide. The Syrian hamsters were immunized three times at three-week intervals with W-PreS-O or with aluminum hydroxide (placebo), and then they were infected with Omicron BA.1. Non-infected and non-vaccinated animals served as controls. Neutralizing antibody (nAB) titers, weight, lung symptoms (i.e., edema and pneumonia index), and viral loads, as measured using RT-PCR in the upper and lower respiratory tracts, were determined. In addition, infectious virus titers from the lungs were measured using a plaque-forming assay. W-PreS-O-vaccinated hamsters developed robust nABs against Omicron, showed almost no development of pneumonia, and had significantly reduced infectious virus titers in the lungs. Importantly, the viral loads in the nasal cavities of W-PreS-O-vaccinated hamsters were close to or above the PCR cycle threshold considered to be non-infectious. Our data provide compelling evidence demonstrating that the W-PreS-O vaccine has protective effect against Omicron in a Syrian hamster in vivo infection model. W-PreS-O is therefore a highly promising candidate vaccine for Omicron infections, and it should be further evaluated in clinical studies.

The cytokine-producing nucleotide-binding domain leucine-rich repeat and pyrin-containing receptor 3 (NLRP3) inflammasome is generally recognized to play a central role in the immune response to vaccination and NLRP3 activity is known to be increased by both aluminum adjuvants and by oxidative stress. Thus, the presence of oxidative stress may place individuals at higher risk for exaggerated or prolonged inflammatory responses and related side effects from vaccination. We here examine the relationship between oxidative stress and NLRP3 inflammasome activity, particularly in the context of aluminum-adjuvanted vaccines, and its implications for subpopulations of individuals with restricted antioxidant capacity.

For decades, compounds present in foods and beverages have been implicated in the etiology of human cancers. The International Agency for Research on Cancer (IARC) continues to classify such agents regarding their potential carcinogenicity in humans based on new evidence from animal and human studies. Furfuryl alcohol and β-myrcene belong to these potential human carcinogens due to be evaluated. The major source of furfuryl alcohol in foods is thermal processing and ageing of alcoholic beverages while β-myrcene occurs naturally as a constituent of essential oils of plants such as hops, lemongrass and derived products. This study aimed to summarize the occurrence of furfuryl alcohol and β-myrcene in foods and beverages using data from own nuclear magnetic resonance (NMR) analysis and literature review. The highest content of furfuryl alcohol was found in coffee beans (>100 mg/kg) and in some fish products (about 10 mg/kg) while among beverages, wines contained between 1–10 mg/L with 8 mg/L in pineapple juice. The content of β-myrcene was highest in hops. In conclusion, the data about the occurrence of the two agents is either very old or based on single sample analysis, and currently judged as insufficient for exposure and risk assessment. The results of this study point out the food and beverage groups that may be considered for future monitoring of furfuryl alcohol and β-myrcene.

This paper investigates calendar anomalies, volatility patterns, and the best forecasting model for predicting volatility in the cryptocurrency market, focusing on ten prominent cryptocurrencies: Binance USD, Bitcoin, Binance Coin, Cardano, Dogecoin, Ethereum, Solana, Tether, USD Coin, and Ripple. Spanning from January 2016 to December 2023, the study utilizes sophisticated statistical models such as GARCH (p,q), EGARCH (p,q), and GJR-GARCH (p,q) to analyze precise changes in market dynamics and the impact of day-of-week fluctuations on cryptocurrency returns. Empirical evidence reveals significant findings regarding the persistence of volatility, positive and negative news effects on volatility, and day-of-week effects on cryptocurrency returns. Post-COVID-19, Sunday emerges as the least volatile day for cryptocurrencies, while Thursdays and Tuesdays exhibit greater volatility. Binance, Ethereum, Dogecoin, and Tether show anomalies where returns on Tuesday and Thursday significantly differed from those on other days of the week. Many other currencies, like the USD coin, Cardano, and Ripple, show anomalies only in the pre-COVID-19 period. The findings highlight the best forecast model for volatility for each top cryptocurrency, offering practical implications for investors, traders, regulators, and policymakers. These insights emphasize the importance of understanding and addressing calendar anomalies in the cryptocurrency market for informed decision-making, trading strategies, regulatory frameworks, and market stability.

CrHZSM-5 was placed in an electric field with appropriate strength in a quartz packed bed reactor with CO2 as oxidant to analyze its catalytic activity. Olefin yield increases with decrease in band gap since lattice oxygen mobility increases by reducing band gap. Fermi level change at the catalyst surface affects the catalytic activity. One way to change Fermi level is use electric field. In high voltage electric field, energy band was curved, bending of the energy band promoted the activity and Fermi level position is increasing. The CCD experiments were carried out with Design-Expert 7.3 software to determine the interaction between four operating variables, namely: temperature, electrical current, gap distance and metal loading. The levels of the independent variables were: temperature (550-700 °C), electrical current (0-12 mA), gap distance (6-14 mm), metal loading (0.5-7.5 %wt.). The conversion of LPG (Liquefied petroleum gas) was greatly increased by weak and effective application of an electric field to the catalyst bed. The obtained results indicated that the maximum yield value (46.94%) can be achieved under 673.66 °C, input electrical current of 11.01 mA, gap distance of 6.55 mm and metal loading of 3.98 wt.%.

Spermatogonial stem cells (SSCs) are the only primitive spermatogonial cells in males that can naturally transmit genetic information to their offspring and replicate throughout their lives. Phospholipase D family member 6 (PLD6) has recently been found to be a surface marker for SSCs in mice and boars; however, it has not been validated in cattle. The results of RT-PCR and qRT-PCR found that the relative expression of PLD6 gene in the testicular tissues of 2-year-old Simmental calves was significantly higher than that of 6-month-old calves. Immunofluorescent staining further verified the expression of PLD6 protein in bovine spermatogenic cells like germ cell marker VASA. Based on multiple bioinformatic databases, PLD6 is a conservative protein which has high homology with mouse Q5SWZ9 protein. It is closely involved in the normal functioning of the reproductive system. Molecular dynamics simulation analyzed the binding of PLD6 as a phospholipase to cardiolipin (CL), and PLD6-CL complex showed high stability. The protein interaction network analysis showed that there is a significant relationship between PLD6 and piRNA binding protein. PLD6 acts as an endonuclease and participates in piRNA production. In addition, PLD6 in bovine and mouse testes has a similar expression pattern with the spermatogonium-related genes VASA and PIWIL2. In conclusion, these analyses imply that PLD6 has a relatively high expression in bovine testes and could be used as a biomarker for spermatogenic cells including SSCs.

Nonwovens made of recycled carbon fibers (rCF) and thermoplastic (TP) fibers have excellent economic and ecological potential. In contrast to new fibers, recycled carbon fibers are significantly cheaper and the CO2 footprint is mostly compensated by energy savings in the first product life cycle. The next step for this promising material is its industrial serial use. Therefore the process chain from fiber to composite material is analyzed. Initially rCF length at different positions during the carding process is measured. Thereafter the influence of the TP fibers onto processing, fiber shortening and mechanical properties is evaluated. At last several nonwovens with different TP fibers and fiber volume contents between 15 vol.-% and 30 vol.-% are produced, consolidated by hot pressing and tested by 4-point bending to determine the mechanical values. The fiber length reduction ranges from 20.6 % to 28.4 %. TP fibers cushion the rCF against mechanical stress but hold rCF fragments back due to their crimp. The resulting bending strength varies from 301 MPa to 405 MPa and the stiffness from 16.3 GPa to 30.1 GPa. Design recommendations for reduced fiber shortening are derived as well as material mixtures which offer better homogeneity and higher mechanical properties.

This article discusses the use of a hand held electronic nose to obtain information on the presence of some aromatic defects in natural cork stoppers, such as haloanisoles, alkylmethoxypyrazines and ketones. The proposed prototype has been developed as an instrumentation system with up to eight commercial gas sensors. Machine learning algorithms such as k-nearest neighbors and artificial neural networks has been used. The use of this system tries to improve the current aromatic defect detection process in the cork stopper industry, which is done by gas chromatography or human test panels.

Biomimetic materials are substances that replicate natural structures. There are several methods for producing such materials with highly developed surfaces from a wide range of polymers, but electrospinning is of particular interest due to its simplicity of implementation and the ability to modify the produced fibrous materials resembling structures found in living organisms. This study explores new biomimetic materials based on polyhydroxyalkanoates, specifically poly-3-hydroxybutyrate, modified with chlorophyll derivatives. The research investigates the impact of chlorophyll derivatives on the morphology, supramolecular structure, and key properties of nonwoven materials. The obtained results are of interest for the development of new biomimetic environmentally friendly materials for biomedicine with special properties.

Thermal fluctuations in two-dimensional (2D) isotropy systems at non zero finite temperatures can destroy the long-range (LR) magnetic order due to Mermin-Wanger theory. Interestingly, the magnetic anisotropy related to spin-orbit coupling (SOC) could stabilize magnetic order in 2D systems. Recently, 2D FexGeTe2 (3≤x≤7) with high curie temperature (TC), as a typical 2D van der Waals metallic ferromagnet, has not only made significant progress in synthetic methods and controlling ferromagnetism (FM), but also actively explored many device applications. In this Review, we introduce six experimental methods, ten ferromagnetic modulation strategies, and three spintronic devices of 2D FexGeTe2 materials. Overall, we have outlined the challenges and potential research directions in this field.

The paper presents an innovative hexapod walking robot built with 3-UPU parallel mechanism. In the robot, the parallel mechanism is used as both an actuator to generate walking and also a connecting body to connect two groups of three legs, thus enables the robot to walk with simple gait by very few motors. In the paper, the forward and inverse kinematics solutions are obtained. The workspace of the parallel mechanism is analyzed using limit boundary search method. The walking stability of the robot is analyzed, which yields the robot’s maximum step length. The gait planning of the hexapod walking robot is studied for walking on both flat and uneven terrains. The new robot, combining the advantages of parallel robot and walking robot, has a large carrying capacity, strong passing ability, flexible turning ability, and simple gait control for its deployment for uneven terrain.

The treatment of acute myeloid leukemia (AML) with adverse genetics remains unsatisfactory, with very low response rates to standard chemotherapy and shorter durations of remission commonly observed in these patients. The complex biology of AML with adverse genetics is continuously evolving. Herein, we discuss recent advances which have investigated the contribution of cell intrinsic mechanisms as well as of the immune system to myeloid leukemogenesis in this specific subset of AML. We focus on the biological rationales for combining targeted therapy and immunotherapy, which are currently being investigated in ongoing trials, and could hopefully ameliorate the poor outcomes for these patients

The Upper Jurassic (Oxfordian Age) Smackover Formation is a significant source for hydrocarbon production in southwest Alabama. Brooklyn Field is in southeast Conecuh County, Alabama and has been a major producer of oil and natural gas for the state. The Smackover is a carbonate formation that is divided into seven distinct lithofacies. In southwest Alabama, the Smackover Formation is heavily influenced by paleotopography from the underlying Paleozoic rocks of the Appalachian system. The goal of this study is to determine elemental ratios in rock core within the Smackover Formation using a X-ray fluorescence (XRF) handheld scanner, to correlate between lithofacies in the Smackover Formation and elementally characterize the upper oolitic grainstone reservoir and the lower thrombolite boundstone. Eight wells were used for the study within Brooklyn Field and Little Cedar Creek fields. Cores from the eight wells were scanned on six-inch intervals. Chemical logs were produced to show elemental weights in relation to depth and lithofacies. Well data collected for chemical signatures within producing zones were correlated to reservoir lithofacies and porosity. Aluminum, silicon, calcium, titanium, and iron were the most significant (>95% confidence level) predictors of porosity and is related to the depositional environment and subsequent diageneses of the strata. XRF data suggests relative enrichments in iron, titanium, and potassium may be related to deposition in relatively restricted marine waters.

Background/aims: Prior research identified a significant association between heart disease and metabolic dysfunction-associated liver steatohepatitis (MASLD), but the mechanisms are unclear. This study aims to search predictive biomarkers for grade I left ventricular diastolic dysfunction (LVDD), an early stage of heart failure (HF), in type 2 diabetes mellitus (T2DM) patients. Methods: This single-center, prospective observational study screened 73 T2DM patients for grade 1 LVDD and MASLD using 2D echocardiography, tissue analysis, spectral color Doppler, and Fibromax. Results: The study analyzed 50 patients (mean age 58±11.3 years) with a median diabetes duration of 7 years, abdominal obesity (mean BMI 34.4±5.9 kg/m2), and a mean HbA1c of 7.9±1.5%. The prevalence of grade I LVDD, fibrosis, mild steatosis, moderate to severe liver steatosis, mild MASLD, and moderate MASLD was 54%, 44%, 14%, 80%, 43%, and 34%, respectively. Regression analysis revealed that grade 1 LVDD was positively associated with age, Fibrotest, ɑ2-macroglobulin, epicardiac adipose tissue (EAT), and negatively associated with lateral s`, E wave, E/e`, E/A, medium E`, and septal e` (p&lt; 0.05 for all). ɑ2-macroglobulin &gt; 1.92 g/L (AUROC= 0.782, sensitivity 70.4%, specificity 81.2%) and fibrotest score &gt; 0.11 (AUROC 0.766, sensitivity 92.6%, specificity 56.2%) were significant predictors of grade I LVDD. Conclusion: HF is a multifaceted disorder associated with multisystem organ damage, including nonalcoholic MASLD. Although the underlying mechanisms remain unclear, innovative non-invasive biomarkers, such as ɑ2-macroglobulin or fibrotest, could concurrently indicate liver stiffness and the likelihood of grade I LVDD, an early, asymptomatic HF stage in T2DM patients.

This study focused on the impact of the treatment with the hypomethylating agent 5-Azacitidine on the redox status and inflammation in 24 MDS patients. Clinical and genetic features of MDS patients were recorded and peripheral blood samples were used to determine the activity of the endogenous antioxidant defense system (superoxide dismutase, SOD, catalase, CAT, glutathion peroxidase, GPx, and reductase, GRd, activities), markers of oxidative damage (lipid peroxidation, LPO, and advanced oxidation protein products, AOPP). Moreover, pro-inflammatory cytokines and plasma nitrite plus nitrate levels as markers of inflammation, and CoQ10 plasma levels, were also measured. Globally, MDS patients showed less redox status in terms of a reduction in the GSSG/GSH ratio and in the LPO levels, and increased CAT activity compared with healthy subjects, with not changes in SOD, GPx and GRd activities, and AOPP levels. When analyzed the evolution from early- to advanced stages of the disease, the GPx activity, GSSG/GSH ratio, LPO and AOPP increased, with a reduction in CAT. GPx changes were related with the presence of risk factors such as high-risk IPSS-R or mutational score. Besides, there was an increase in IL-2, IL-6, IL-8 and TNF-α plasma levels, with further increase of IL-2 and IL-10 from early to advanced stage of the disease. However, we did not observe any association between inflammation and oxidative stress. Finally, 5-azacitidine treatment generates oxidative stress in MDS patients, without affecting inflammation levels, suggesting that oxidative status and inflammation are two independent processes.

Cartilage regeneration requires a balance of anabolic and catabolic processes. This study examined the susceptibility of fibromodulin (FMOD) and lumican (LUM) to degradation by MMP-13, ADAMTS-4 and ADAMTS-5, the three major degradative proteinases in articular cartilage in osteoarthritis (OA). Immunolocalisation of FMOD and LUM in foot sections of developmental cartilages demonstrated prominent localisations in metatarsal and phalangeal foetal rudiment cartilages and growth plate. An MMP-13 neoepitope antibody (TsYG11) demonstrated localisation of MMP-13 cleaved FMOD in the hypertrophic chondrocytes of the metatarsal growth plate. FMOD was more prominently localised in the superficial cartilage of normal and fibrillated zones in OA cartilage, TsYG11 positive FMOD was located deeper in the cartilage samples. Ab TsYG11 also identified FMOD fragmentation in Western blots of extracts of normal and fibrillated cartilage and total knee replacement OA cartilage. The C-terminal anti-FMOD used in this study (PR-184) failed to identify FMOD fragmentation due to C terminal processing, an equivalent Ab to the C-terminus of LUM (pAb PR-353) identified 3 prominent LUM fragments in OA human knee cartilages. In-vitro digestion of human knee cartilage with MMP-13, ADAMTS-4 and ADAMTS-5 generated equivalently sized FMOD fragments of 54, 45 and 32kDa to those in blots of OA cartilage, LUM was not less susceptible to fragmention in in-vitro digestions however Ab PR-353 detected N-terminally processed LUM fragments of 39, 38 and 22 kDa in 65-80 year old OA knee cartilage. FMOD and LUM were differentially processed during in-vitro digestions with MMP-13, ADAMTS-4 and ADAMTS-5 with FMOD susceptible to degradation by MMP-13, ADAMTS-4 and to a lesser extent ADAMTS-5 however LUM was less susceptible to fragmentation. FMOD was processed by MMP-13 in metatarsal and phalangeal foetal rudiment developmental cartilages and growth plate indicating a role in skeletogenesis.

Luminal breast cancer has a high incidence worldwide and is a severe health threat. Estrogen receptor alpha (ER-α) is activated by 17β-estradiol (E2), and its overexpression promotes cancerous characteristics. Luminal breast cancer is an epithelial type; however, the cytokine IL-6 secreted by cells from the tumor microenvironment stimulates the epithelial to mesenchymal transition (EMT) and promotes metastasis. Also, IL-6 decreases ER-α levels, favoring the tamoxifen (TMX) resistance development. However, genes under E2 regulation continue expressing even though this receptor is absent. GPR30 is an alternative E2 receptor present in both luminal and aggressive triple-negative breast cancer and is related to TMX resistance and cancer progression. The roles of GPR30 and IL-6 on metastasis have been individually established; however, their interplay remains unexplored. This study aims to elucidate the role of GPR30 in IL-6-induced metastatic properties in MCF-7 luminal breast cancer cells. Results showed that GPR30 contributes to the E2-induced MCF-7 proliferation because its inhibition with the antagonist G15 and the Pertussis toxin (PTX) diminished it. Besides, GPR30 upregulated vimentin and downregulated E-cadherin levels in MCF-7 and in TMX-resistant (R-TMX) cells and is also involved in the IL-6-induced migration, invasion, and TMX resistance in MCF-7 cells. In addition, in MDA-MB-231 triple-negative cells, both basal and IL-6-induced metastatic properties were related to GPR30 activity. These results indicate that the GPR30 receptor regulates the EMT induced by IL-6 in breast cancer cells.

Oxidative neurodegeneration causes various neuronal diseases including Alzheimer's disease, Parkinson's disease, and Huntington's disease. This study aimed to demonstrate the protective effect of leaf extracts of Allium senescens on 6-hydroxydopamine (6-OHDA)-stressed SH-SY5Y cells, known as an optimal cell for neurotoxic research. Levels of apoptotic markers were evaluated using quantitative polymerase chain reaction (qPCR) and flow cytometry. The localization of apoptotic cells in vivo was analyzed using whole-mount immunochemistry and the terminal deoxynucleo-tidyl transferase dUTP nick end labeling assay. Additionally, reactive oxygen species (ROS) pro-duction was estimated using flow cytometry. 6-OHDA induced ROS production in neuroblast cells and in vivo, but treatment with the extract protected against the 6-OHDA-induced increase in ROS levels. Under oxidative stress, the extract performs three protective functions: decreases ROS production, prevents mitochondrial apoptosis, and protects the central and ventral nervous systems. These results also suggest that the extract can be useful for the development of functional foods for the prevention of neural damage due to oxidative stress.

Lindera obtusiloba Blume has several activities, such as anti-inflammatory, anti-allergic, anti-tumor, anti-wrinkle, and antioxidant activities. Interleukin-6 (IL-6) is a classic pro-inflammatory cytokine that is associated with various functions, such as proliferation, invasion, inflammatory responses and functions within antioxidant defence systems. In this study, we investigated IL-6-induced STAT3 activation of lignan compounds isolated from L. obtusiloba. The structures of the isolated compounds were elucidated via spectroscopic nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI-MS). As a result, seven lignans were identified from L. obtusiloba. All the isolated compounds (1-7) were evaluated for their IL-6-induced STAT3 inhibitory effects in Hep3B cells using a luciferase reporter assay. Of the isolates, compounds 1 and 5 showed inhibitory effects against IL-6-stimulated STAT3 activation. Furthermore, the mRNA expression levels of inflammation-related genes such as CRP, IL-1b, and SOCS3 were significantly reduced by exposure to compound 1 and 5. The protein levels of p-STAT3, p-JAK2 in IL-6 induced U266 cells were regulated in the presence of lignans derived from Lindera obtusiloba by western blot assay. Based on the results, this study of L. obtusiloba demonstrates that the species has promise as a bioactive candidate for the treatment of IL-6-induced STAT3-related disease.

This contribution was devoted to unveil the strain rate sensitivity (SRS) of G18NiCrMo3-6 cast steel in tension/compression asymmetry. For that purpose, detailed mechanical characterization tests were conducted providing a process window covering quasi-static and medium strain rate regimes (0.001, 0.1, 10 [ s¯¹]) in tension and compression states. By means of this experimental ef-fort, the SRS of the material could be extracted by a function of strain and strain rate which ena-bling to create a mathematical expression to easily be implemented as a state variable for constitu-tive material modeling. Finally, a pressure and rate dependent constitutive material model on the basis of Cocks'89 yield locus definition was created by a subroutine (UMAT) file and the material parameters were verified with respect to the experimental data. The UMAT file also takes into account the tension/compression asymmetry in yielding to handle the effect of porous media plas-ticity concept. The predictions of the proposed material model are quite in line with the experi-mental outputs.

Plant species with anti-inflammatory properties might play an essential role in combatting COVID-19 via reducing cytokine storms. We aimed to review the extant evidence of the potential therapeutic efficacy of natural products against cytokine storms by inhibiting interleukin-6 (IL-6) as a major pathological mediator. Data were collected following an electronic search in major databases (Pubmed, Scopus, Web of Science, Google Scholar) and also preprint articles on preprint and medRxiv servers by using a combination of relevant keywords. Seventeen active compounds and medicinal plants were found and reviewed in the present review. Results of both in-vivo and in-vitro experiments conducted on these compounds showed that Phillyrin, SMFM, Qiangzhi decoction, curcumin, Shen-Fu, Forsythia, and Alpha-Mangostin inhibit the production of IL-6. Andrographolide and Liu Shen Wan have an inhibitory effect on releasing this agent, while Ilex Asprella and Deoxy-11,12-didehydroandrographolide and naringin reduce the expression of IL-6. Theaflavin and Cholorogenic acid inhibit the secretion of IL-6, Xuebijing, and Chai-Hu-Gui-Zi-Gan-Jiang-Tang and Lipanpaidu prescription can reduce the serum level of IL-6. These agents also effectively improve infected lungs, increase survival rates, and minimize tissue damage. Medicinal plants and their phytochemical ingredients with down-regulatory effects on the expression of IL-6 have a potential influence on the inhibition of cytokine storms during viral infection caused by COVID-19. Therefore, phytochemicals could be regarded as promising candidates for managing cytokine storm inflammatory responses due to COVID-19 infection.

Background: Multidrug-resistant bacteria present resistance mechanisms against β-lactam antibiotics, such as Extended-Spectrum Beta-lactamases (ESBL) and Metallo-β-lactamases enzymes (MBLs) operon encoded in Gram-negative species. Likewise, Gram-positive bacteria have evolved other mechanisms through mec genes, which encode modified penicillin-binding proteins (PBP2). This study aimed to determine the presence and spread of β-lactam antibiotic resistance genes and the microbiome circulating in Quito’s Public Transport (QTP). Methods: A total of 29 station turnstiles were swabbed to extract the surface environmental DNA. PCRs were performed to detect the presence of 13 antibiotic resistance genes and to identify 16S rDNA barcoding, followed by clone analysis, Sanger sequencing and BLAST search. Results: ESBL genes blaTEM-1 and blaCTX-M-1 and MBL genes blaOXA-181 and mecA were detected along QPT stations. Two subvariants were found for blaTEM-1, blaCTX-M-1, and blaOXA-181. Almost half of the circulating bacteria found at QPT stations were common human microbiota species including those classified by the WHO as pathogens of critical and high-priority surveillance. Conclusions: β-lactam antibiotic resistance genes are widely spread throughout QPT. This is the first report of blaOXA-181 in environmental samples in Ecuador. Moreover, we detected a new putative variant of this gene. Some commensal coagulase-negative bacteria may have a role as mecA resistance reservoirs

The three-point bending behavior of a single Au nanowire deformed with an atomic force microscope was monitored by coherent X-ray diffraction using a sub-micrometer sized hard X-ray beam. While three-dimensional reciprocal-space maps were recorded before and after deformation by standard rocking curves, they were measured by scanning the energy of the incident X-ray beam during deformation at different loading stages. The mechanical behavior of the nanowire is visualized in reciprocal space and a complex deformation mechanism is described. In addition to the expected bending of the nanowire, torsion is detected. Bending and torsion angles are quantified from the high resolution diffraction data.

Abstract: Comparing outcrop data to laboratory results is important to verify and validate experiments of analogue and reservoir materials especially regarding conditions for deformation experiments. This is important better understand highly complex carbonate reservoir strata and their response to changes in subsurface conditions, reducing subsurface uncertainty. This study develops methods to allow for a more straightforward comparison of outcrop data (m-scale) with experimentally created fracture arrays developed in cylindrical samples (cm-scale). The main objective is to assess usefulness of experimentally-produced fracture networks as analogues for subsurface structures, typically at the meter and above scale by developing new techniques to use the lab deformation. It analyses key characteristics of laboratory-induced fracture networks by adapting scanline methods to use with x-ray tomography (XRT) images to allow for comparison with outcrop and field data. To test and verify these new methods two low permeability carbonate samples were used for deformation testing and analysis. Applying the different scanline methods we show that they can be used to analyse lab induced fractures (mm to cm-scale) identified in XRT images for comparison with outcrop data (m-scale). In addition, these methods also allow for quantification of fracture network attributes e.g. fracture spacing, fracture apertures, orientation. This new data bridges the gap between micro-scanlines using thin sections and outcrop scanlines.

This study investigates the potential of natural compounds against HIV-1 protease, a critical enzyme in the replication cycle of human immunodeficiency virus type 1 (HIV-1). HIV-1 protease is essential for cleaving large precursor proteins into smaller functional proteins necessary for viral maturation and infectivity. Protease inhibitors, specifically targeting HIV-1 protease, effectively suppress viral replication, aiding in the management of HIV infection. Using the SWISS DOCK Server, several natural compounds were investigated for their potential as inhibitors of HIV-1 protease. Docking results revealed that Amentoflavone showed excellent binding affinity with high Estimated ΔG values, suggesting its potential as an inhibitor of HIV-1 protease. Additionally, Amentoflavone exhibited similar promising results when tested against Roussarcoma virus protease. These findings indicate the potential of Amentoflavone as a natural compound against HIV and warrant further investigation into its therapeutic applications.

Landslide risk mitigation is limited by data scarcity. This could be improved using continuous landslide detection systems. In order to investigate which image types and machine learning (ML) models are most useful for landslide detection in a Norwegian setting, we compared the performance of five different ML models, for the Jølster case study (30-July-2019), in Western Norway. These included three globally pre-trained models; i) the Continuous Change Detection and Classification (CCDC) algorithm, ii) a combined k-means clustering and Random Forest classification model, and iii) a convolutional neural network (CNN), and two locally-trained models, including; iv) Classification and Regression Trees and v) a U-net CNN model. Images used included Sentinel-1, Sentinel-2, digital elevation model (DEM) and slope. The globally-trained models performed poorly in shadowed areas, and were all outperformed by the locally-trained models. A maximum Matthew’s correlation coefficient (MCC) score of 89% was achieved with model v, using combined Sentinel-1 and -2 images as input. This is one of the first attempts to apply deep-learning to detect landslides with both Sentinel-1 and -2 images. Using Sentinel-1 images only, the locally-trained deep-learning model significantly outperformed the conventional ML model. These findings contribute towards developing a national continuous monitoring system for landslides.

We present a study of the radio variability of bright, $S_{1.4}\geq100$ mJy, high-redshift quasars at $z\geq3$ on timescales up to 30--40 years. The study involved simultaneous RATAN-600 measurements at frequencies of 2.3, 4.7, 8.2, 11.2, and 22.3 GHz in 2017--2020. In addition, data from the literature were used. We have found that the variability index $V_S$ of the quasars ranges from 0.02 to 0.96, with about half of the objects in the sample showing a variability index in the range of 0.25--0.50, which is comparable to that of the blazars at lower redshifts. The distribution of $V_S$ at 22.3 GHz is significantly different from that at 2.3--11.2 GHz, which may be attributed to the fact that a compact AGN core dominates at the source's rest frame frequencies greater than 45 GHz, leading to higher variability indices obtained at 22.3 GHz (the $V_S$ distribution peaks around 0.4) compared to the lower frequencies (the $V_S$ distribution peaks around 0.1--0.2). Several source groups with distinctive variability characteristics were found using cluster analysis of quasars. We propose 7 new candidates for gigahertz peaked-spectrum (GPS) sources and 5 new megahertz peaked-spectrum (MPS) sources based on their spectrum shape and variability features. Only 6 out of 23 sources previously reported as GPS demonstrate a low variability level typical of classical GPS sources ($V_{S} < 0.25$) at 4.7--22.3~GHz. When excluding the highly variable peaked-spectrum blazars, we expect no more than 20\% of the sources in the sample to be GPS candidates and no more than 10\% to be MPS candidates.

Anderson – Fabry disease (AFD) is a rare, X-linked lysosomal storage disorder caused by a mutation in the α-Galactosidase A gene resulting in α-Galactosidase A enzyme (α-Gal A) deficiency. The metabolic defect leads to progressive accumulation of glycosphingolipids and structural and functional impairment of affected organs. Due to the inheritance pattern, male patients are hemizygous with more severe manifestations of the disease as compared to females who in most cases are heterozygous with delayed and variable clinical presentation caused by uneven X – chromosome inactivation. Fabry disease cases are often identified by targeted screening programs in high-risk groups, such as in patients with end-stage renal disease, premature stroke or unexplained cardiomyopathy. Here we describe a unique case of homozygous female patient identified by a nationwide screening program in hypertrophic cardiomyopathy patients. Before the systematic screening, the patient had a diagnosis of hypertrophic obstructive cardiomyopathy and was treated accordingly including alcohol septal ablation to reduce the obstructive gradient. The confirmation of Fabry disease has led to discovery of the same variant in several members of her family. The identified variant was c.644A>G, p.Asn215Ser (N2015S) known to cause predominant cardiac involvement with late onset of the disease. The variant is amenable for an oral therapy by the small molecular chaperone migalastat which was started, then interrupted for recurrence of patient´s migraine and then re-initiated again after two years. During this period the patient received enzyme replacement therapy by agalsidase beta but developed a progressively worsening venous access. Our case illustrates the importance of systematic screening of patients with clinical evidence of hypertrophic cardiomyopathy in whom routine diagnostic process fails to discover Fabry disease, in particular variants with late onset cardiac manifestations. Many of the late onset variants are amenable for orally active therapy by migalastat which significantly improves the comfort of the treatment. Its long term results are analysed by a large international “Follow-me” registry which was designed to verify the validity of pivotal trials with migalastat in Fabry disease.

Viruses pose a great threat to people’s lives. Enterovirus A71 (EV-A71) infects children and infants all over the world with no FDA-approved treatment to date. Understanding the basic mechanisms of viral processes aids in selecting more efficient drug targets and designing more effective antivirals to thwart this virus. The 5´-untranslated region (5’-UTR) of the viral RNA genome is composed of a cloverleaf structure and an internal ribosome entry site (IRES). Cellular proteins that bind to the cloverleaf structure regulate viral replication, while those that bind to the IRES also known as IRES trans-acting factors (ITAFs) regulate viral translation. In this review, we survey the cellular proteins currently known to bind the 5’-UTR and influence viral translation and replication with emphasis on comparing proteins’ functions and localizations pre- and post-(EV-A71) infection. Comprehensive understanding of how the host cell’s machinery is hijacked and reprogrammed by the virus to facilitate its replication is crucial for developing effective antivirals.

The search for a continuous continental record of interglacial periods in semi-arid regions is problematic due to the absence of stable and continuous sedimentary systems over time in this type of climate. In this work, a relatively stable basin is described and analyzed during the last interglacial in a semi-arid region of the western Mediterranean. For this purpose a geomorphological, stratigraphic and sedimentological study has been carried out, with dating through 230Th. A semi-endorrheic Pleistocene basin has been identified, with two units that correspond to a fluvial-lacustrine system (unit P1) and an alluvial system (unit P2). Unit P1 has been dated in the MIS 5e interglacial episode. A framework is described in which the Aljezares Quaternary basin can be considered as a possible source of paleoenvironmental and paleoclimatic information in semi-arid regions from the last interglacial period in future studies.

Trace amine-associated receptor 5 (TAAR5) is a G protein-coupled receptor that belongs to the TAARs family (TAAR1-TAAR9). TAAR5 is expressed in the olfactory epithelium and is responsible for sensing 3-methylamine (TMA). However, recent studies showed that TAAR5 is also expressed in the limbic brain regions and is involved in the regulation of emotional behaviour and adult neurogenesis, suggesting that TAAR5 antagonism may represent a novel therapeutic strategy for anxiety and depression. We used the AtomNet® model, the first deep learning neural network for structure-based drug discovery, to identify putative TAAR5 ligands and tested them in an in vitro BRET assay. We found two mTAAR5 antagonists with low to submicromolar activity that are able to inhibit the cAMP production induced by TMA. Moreover, these two compounds also inhibited the mTAAR5 downstream signalling, such as the phosphorylation of CREB and ERK. These two hits exhibit drug-like properties and could be used to develop further more potent TAAR5 ligands with putative anxiolytic and antidepressant activity.

Enhanced permeation retention (EPR) was a significant milestone discovery by Maeda et al. paving the road for the emerging nanomedicine as a powerful tool in the fight against cancer. Sildenafil is a potent inhibitor of phosphodiesterase 5 (PDE-5) used for treatment of erectile dysfunction (ED) through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. Overexpression of PDE-5 was reported in lung, colon, metastatic breast cancers and bladder squamous carcinoma. Accordingly, there has been a growing interest in using sildenafil as monotherapy or chemoadjuvant in EPR augmentation and management of different types of cancer. Sildenafil had been reported to increase the sensitivity of tumor cells of different origins to the cytotoxic effect of chemotherapeutic agents with augmented apoptosis mediated through inducing the expression of Bad and Bax proapoptotic proteins. It was also reported that the use of sildenafil prior to the administration of Doxorubicin (DOX) increased its EPR-related concentration in breast cancer tissues by 2 folds. Further, a substantial reason of anticancer chemotherapeutic failure is due to multidrug resistance (MDR), exacerbated by the overexpression of ATP-binding cassette (ABC) transporters such as ABCB1 and ABCCs. Sildenafil has demonstrated inhibitory effects on the efflux activity of ABCC4, ABCC5, ABCB1, and ABCG2, ultimately reversing MDR caused by these transporters. In this review, we critically examine the overall potential of sildenafil in enhancing EPR-based anticancer drug delivery pointing up the outcome of the most important related preclinical and clinical studies.

A newly synthesized upper rim azocalix[4]arene, namely, 5,11,17,23-tetra[(4-ethylacetoxyphenyl) (azo)]calix[4]arene, CA-AZ was fully characterized and its chromogenic and selective properties for anions are reported. The receptor is selective for the fluoride anion and its mode of interaction in solution is discussed. The kinetics of the complexation process was found to be very fast as reflected in the immediate color change observed with a naked eye resulting from the receptor-anion interaction. Emphasis is made about the relevance in selecting a solvent in which the formulation of the process is representative of the events taking place in the solution. The composition of the fluoride complex investigated by UV/VIS spectrophotometry, conductance measurements and titration calorimetry was 1:1 and the thermodynamics of complexation was determined. The fluoride complex salt was isolated, and a detailed investigation was carried out to assess its ability to remove CO₂ from the air. Recycling of the complex was easily achieved. Final conclusions are given.

Increasing photon absorption by capturing light is an important way to increase the efficiency of photovoltaic devices. In this regard, the small optical band gap (Eg) and high absorption coefficient of Se-containing thin nanofilms make them ideal for next generation photovoltaic devices based on selenides. This study reports on chemical synthesis processes in a bath for the insertion of amorphous selenium into polyamide-6 (PA 6) matrix and the effect of incorporation of Cd2+ and Ag+ on the structural, morphological and optical properties. The resulting films had a pyramidal structure of single crystals, nanosized particles of nonspecific shape, agglomerated and indistinct grains. ATR-FTIR spectroscopy revealed the interaction between PA 6 and inorganic components, which causes obvious conformational changes in PA 6 chains. The data of X-ray diffraction analysis, depending on the stage of synthesis, showed a mixture of various compounds: Se8, CdSe, Ag2Se and Ag. This may explain the observed optical properties. The optical properties of the composites indicate a shift in the band gap from 4.46 eV for PA 6 to 2.23-1.64 eV upon stepwise insertion of amorphous Se, Cd2+ and Ag+ ions. Eg is conveniently located in the visible region of solar energy, making the obtained nanofilms ideal for solar energy harvesting.

Abstract: Toxicity of emerging organic pollutants to photosystems of aquatic plants are still not well clarified. This study aimed to develop a novel ecotoxicological experimental protocol based on nanoscale electrochemical mapping of photosynthetic oxygen evolution of aquatic plants by SECM (scanning electrochemical microscopy). The protocol was also checked by confocal laser scanning microscopy (CLSM), the traditional Clark oxygen electrode method and chlorophyll fluorescence technique. The typical persistent organic pollutant 2,4-dichlorophenol (2,4-DCP) in water environment and the common aquatic Microsorium pteropus (M. pteropus) were chosen as the model organic pollutant and tested plant, respectively. It was found that the SECM method could well discriminated the responses of stoma micromorphology and spatial pattens of photosynthetic oxygen evolution on single stoma. The shape of stoma blurred with increasing 2,4-DCP concentration, which was in good agreement with the CLSM images. The dose-response curves and IC50 values obtained from the SECM data were verified by the data measured by the traditional Clark oxygen electrode method and chlorophyll fluorescence test. The IC50 value of single stoma oxygen emission of 24 h exposed plant leave, which was derived from the SECM current data (32535 μg L-1), was close to those calculated from the maximum photosynthetic efficiency (Fv/Fm) measured by chlorophyll fluorescence test (33963 μg L-1), and the Clark oxygen electrode method photosynthetic oxygen evolution rate (32375 μg L-1). The 72 h and 96 h 2,4-DCP exposure data further confirmed the reliability of the nanoscale stoma oxygen emission mapping methodology for ecotoxicological assessment. In this protocol, the procedures for how to collect effective electrochemical data and how to extract useful information from the single stoma oxygen emission pattern were well established. This study showed that SECM is a feasible and reliable ecotoxicological tool for evaluation of toxicity of organic pollutants to higher plants with unique nanoscale visualization advantage over the conventional methods.

Gas and power networks are tightly coupled and interact with each other due to physically interconnected facilities. In an integrated gas and power network, a contingency observed in one system may cause iterative cascading failures, resulting in network wide disruptions. Therefore, understanding the impacts of the interactions in both systems is crucial for governments, system operators, regulators and operational planners, particularly, to ensure security of supply for the overall energy system. Although simulation has been widely used in the assessment of gas systems as well as power systems, there is a significant gap in simulation models that are able to address the coupling of both systems. In this paper, a simulation framework that models and simulates the gas and power network in an integrated manner is proposed. The framework consist of a transient model for the gas system and a steady state model for the power system based on AC-Optimal Power Flow. The gas and power system model are coupled through an interface which uses the coupling equations to establish the data exchange and coordination between the individual models. The bidirectional interlink between both systems considered in this studies are the fuel gas offtake of gas fired power plants for power generation and the power supply to LNG terminals and electric drivers installed in gas compressor stations and underground gas storage facilities. The simulation framework is implemented into an innovative simulation tool named SAInt (Scenario Analysis Interface for Energy Systems) and the capabilities of the tool are demonstrated by performing a contingency analysis for a real world example. Results indicate how a disruption triggered in one system propagates to the other system and affects the operation of critical facilities. In addition, the studies show the importance of using transient gas models for security of supply studies instead of successions of steady state models, where the time evolution of the line pack is not captured correctly.

Glutamate transporter-1 (GLT-1) dynamics are implicated in excitotoxicity and Alzheimer's disease (AD) progression. Early stages of AD are often marked by hyperactivity and increased epileptiform activity preceding cognitive decline. Previously, we identified a direct interaction between GLT-1 and Presenilin 1 (PS1) in the brain, highlighting GLT-1 as a promising target in AD research. This study reports the significance of this interaction and uncovers a novel role of GLT-1 in modulating amyloid-beta (Aβ) production. Overexpression of GLT-1 in cells reduces the levels of Aβ40 and Aβ42 by decreasing γ-secretase activity pertinent to APP processing and induces a more "open" PS1 conformation, resulting in decreased Aβ42/40 ratio. Inhibition of the GLT-1/PS1 interaction using cell-permeable peptides produced an opposing effect on Aβ, highlighting the pivotal role of this interaction in regulating Aβ levels. These findings emphasize the potential of targeting GLT-1/PS1 interaction as a novel therapeutic strategy for AD.

Despite substantial evidence supporting the efficacy of prebiotics for promoting host health and stress resilience, few experiments present evidence documenting the dynamic changes in microbial ecology and fecal microbial-modified metabolites across time. Furthermore, the literature reports a lack of reproducible effects of prebiotics on specific bacteria and bacterial-modified metabolites. The current experiments examined whether consumption of diets enriched in prebiotics (galactooligosaccharides, GOS and polydextrose, PDX) compared to control diet, would consistently impact the gut microbiome and microbial-modified bile acids across time and between two research sites. Male Sprague Dawley rats were fed control or prebiotic diets for several weeks, and their gut microbiome and metabolome were examined using 16S rRNA gene sequencing and untargeted LC-MS/MS analysis. Dietary prebiotics altered beta diversity, relative abundances of bacterial genera, and microbially modified bile acids across time. PICRUSt2 analyses identified four inferred functional metabolic pathways modified by prebiotic diet. Correlational network analyses between inferred metabolic pathways and microbial-modified bile acids revealed deoxycholic acid as a potential network hub. All these reported effects were consistent between the two research sites supporting the conclusion that dietary prebiotics robustly changed the gut microbial ecosystem. Consistent with our previous work demonstrating that GOS/PDX reduces the negative impacts of stressor exposure, we propose that ingesting a diet enriched in prebiotics facilitates the development of a health-promoting gut microbial ecosystem.

Paleoclimatic and paleoceanographic studies routinely rely on the usage of foraminiferal calcite through faunal, morphometric and physico-chemical proxies. The application of such proxies presupposes the extraction and cleaning of these biomineralized components from ocean sediments in the most efficient way, a process which is often labor intensive and time consuming. In this respect, in this study we performed a systematic experiment for planktonic foraminiferal specimen cleaning using different chemical treatments and evaluated the resulting data of a Late Quaternary gravity core sample from the Aegean Sea. All cleaning procedures adopted here were made on the basis of their minimum potential bias upon foraminiferal proxies, such as the faunal assemblages, degree of fragmentation, stable isotope composition (δ18O and δ13C) and/or Mg/Ca ratios that are frequently used as proxies for surface-ocean climate parameters (e.g., sea surface temperature, sea surface salinity). Six different protocols were tested, involving washing, sieving, and chemical treatment of the samples with hydrogen peroxide and/or sodium hexametaphosphate (Calgon ®). Single species foraminifera shell weighing was combined with high-resolution Scanning Electron Microscopy (SEM) and synchrotron X-ray Microtomography (SμCT) of the material processed by each of the cleaning protocols, in order to assess the decontamination degree of specimen’s ultrastructure and interior. It appeared that a good compromise between time and cleaning efficiency is the simultaneous treatment of samples with a mixed hydrogen peroxide and Calgon solution, while the most effective way for an almost complete decontaminate of the calcareous components from undesirable sedimentary material is a two-step treatment - initially with hydrogen peroxide and subsequently with Calgon solutions.

Expression of Krüppel–like factor 15 (KLF15), a stress induced transcription factor, is induced during bovine herpesvirus 1 (BoHV-1) reactivation from latency, and KLF15 stimulates BoHV-1 replication. Transient transfection studies revealed KLF15 and glucocorticoid receptor (GR) cooperatively transactivate the BoHV-1 immediate early transcription unit 1 (IEtu1), herpes sim-plex virus type 1 (HSV-1) infected cell protein 0 (ICP0), and ICP4 promoter. The IEtu1 promoter drives expression of bICP0 and bICP4, two key BoHV-1 transcriptional regulatory proteins. Based on these studies, we hypothesized infection is a stressful stimulus that increases KLF15 ex-pression and enhances productive infection. New studies demonstrated that silencing KLF15 impaired HSV-1 productive infection and KLF15 steady state protein levels were increased at late stages of productive infection. KLF15 was primarily localized to the nucleus following in-fection of cultured cells with HSV-1, but not BoHV-1. When cells were transfected with a KLF15 promoter construct and then infected with HSV-1, promoter activity was significantly increased. The ICP0 gene and to a lesser extent bICP0 transactivated the KLF15 promoter in the absence of other viral proteins. In contrast, BoHV-1 or HSV-1 encoded VP16 had no effect on KLF15 pro-moter activity. Collectively, these studies revealed HSV-1 and BoHV-1 productive infection in-creased KLF15 steady state protein levels, which correlated with increased virus production.

Diagnosis of neonatal sepsis is difficult as signs and symptoms are nonspecific. Interleukin-6 (IL-6) is a promising marker for neonatal sepsis. We aimed to test the accuracy of IL-6 in term and preterm infants after 72 hours of life (late-onset sepsis-LOS). We searched for IL-6 diagnostic accuracy studies between 1990 and 2020 using the PubMed database. Study selection was performed. The range of reported IL-6 sensitivities and specificities was 68% to 100% and 28% to 100%, respectively, the median values were 85.7% and 82% from 15 studies including 1306 infants. Subgroup analysis was performed. Sensitivity (87% vs 82%), but not specificity (both 86%), was better in preterm infants than in preterm and term infants. Early sample collection had the highest sensitivity (84%), but the lowest specificity (86%). To assess quality we used a STARD checklist adapted for septic neonates. Limitation of this review include the heterogeneous group of studies on the one side and the small number of studies on the other side that analyzed different combinations of biomarker. We concluded that IL-6 had a good performance especially in the preterm infant population and best results are achieved by measurements at the time of LOS suspicion.

This research is related to the eco-hydrological problems of herbaceous wetland drying and biodiversity loss in the floodplain lakes of the Middle Basin of the Biebrza river (Poland). An experiment was set up, whose main goals were: (i) mapping the vegetation types and the temporarily or permanently flooded areas, and (ii) comparing the usefulness of C-band Sentinel-1A (S1A) and X-band TerraSAR-X/TanDEM-X (TSX/TDX) for mapping purposes. The S1A imagery was acquired on a regular basis using the dual polarization VV/VH and the Interferometric Wide Swath Mode. The TSX/TDX data were acquired in quad-pol, a fully polarimetric mode, during the Science Phase. The paper addresses the following aspects: i) wetland mapping with S1A multi-temporal series; ii) wetland mapping with fully polarimetric TSX/TDX data; iii) comparing the wetland mapping using dual polarization TSX/TDX subsets, i.e. HH-HV, HH-VV and VV-VH; iv) comparing wetland mapping using S1A and TSX/TDX data based on the same polarization (VV-VH); v) studying the suitability of the Shannon Entropy for wetland mapping; and vi) assessing the contribution of interferometric coherence for wetland classification. The experimental results show main limitations of the S1A dataset, while they highlight the good accuracy that can be achieved using the TSX/TDX data, especially those taken in fully polarimetric mode.

Enzymes reliant on pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B6, hold significant importance in both biology and medicine. They facilitate various biochemical reactions, particularly in amino acid and neurotransmitter metabolisms. Vitamin B6 is absorbed by organisms in its non-phosphorylated form and phosphorylated within cells by pyridoxal kinase (PLK) and pyridox-(am)-ine 5'-phosphate oxidase (PNPOx). The flavin mononucleotide dependent PNPOx enzyme converts pyridoxine 5'-phosphate and pyridoxamine 5'-phosphate into PLP. PNPOx is vital for both biosynthesis and salvage pathways in organisms producing B6 vitamers. However, for those depending on vitamin B6 as nutrient, PNPOx participates only in the salvage pathway. Transferring PLP produced by PNPOx to client apo-enzymes is indispensable for their catalytic function, proper folding and targeting to specific organelles. PNPOx activity deficiencies due to inborn errors lead to severe neurological pathologies, particularly neonatal epileptic encephalopathy. PNPOx enzymes from different organisms maintain PLP homeostasis through highly regulated mechanisms, including structural alterations throughout the catalytic cycle and allosteric PLP binding influencing substrate transformation at the active site. Despite shared features, species-specific regulations are evident among PNPOx enzymes.

Space-based Interferometric Synthetic Aperture Radar (InSAR) applications have been widely used to monitor the cryosphere over past decades. Because of temporal decorrelation, interferometric coherence often severely degrades on fast moving glaciers. In addition, higher sensitivity ambiguity occurs in large baseline configurations, which are needed for extracting topographic information over low relief areas such as the surface of a glacier. TerraSAR-X add-on for Digital Elevation Measurement (TanDEM-X) observations, which overcome the temporal decorrelation because of their simultaneous measurements by two satellite constellations, have used a short baseline sufficient for generation of excellent digital elevation models in most locations around the world. However, it remains difficult to estimate detailed topographic characteristics over low slope glacier surfaces because of the relatively less sensitive height ambiguity from the small baselines. In this study, we used the TanDEM-X pursuit monostatic mode with large baseline formation following a scientific phase timeline to develop highly sensitive topographic elevation models of the Petermann Glacier of Northwest Greenland. As expected, coherent interferometric phases (> 0.8) were well maintained over the glaciers despite their fast movement thanks to the nearly simultaneous TanDEM‐X measurements. The height ambiguity, which defined as the altitude difference correspondent to phase change of flattened interferogram, of the dataset was 10.63 m, which is favorable for extracting topography in a low relief region. We validated the TanDEM‐X derived glacial topography by comparing it to the SAR/Interferometric radar altimeter observations acquired by CryoSat‐2 and the IceBridge Airborne Topographic Mapper laser altimeter measurements. Both observations showed very good correlation within a few meters of the offsets (‐12.5 – ‐3.1 m) with respect to the derived glacial topography. Because of highly sensitive ambiguity, we could successfully extract detailed geomorphological features on the glaciers. Routine TanDEM-X observations will be very useful to better understand the dynamics of glacial movements and topographic change.

Psoriasis is a chronic immune-mediated skin disease that involves interaction of both immune and skin cells, and is characterized by cytokine-driven epidermal hyperplasia, deviant differentiation, inflammation and angiogenesis. Because available treatments for psoriasis have significant limitations, dietary products are potential natural sources of therapeutic molecules, which can rescind molecular defects associated with psoriasis and could be developed for its management. Fisetin (3,7,3′,4′- tetrahydroxyflavone), a phytochemical naturally found in pigmented fruits and vegetables has demonstrated pro-apoptotic and antioxidant effects in several malignancies. This study utilized biochemical, cellular, pharmacological and tissue-engineering tools to characterize the effects of fisetin on normal human epidermal keratinocytes (NHEKs), peripheral blood mononuclear cells (PBMC) and CD4+ T lymphocytes in 2D and 3D psoriasis-like disease models. Fisetin treatment of NHEKs dose and time-dependently induced differentiation and inhibited interleukin-22-induced proliferation, as well as activation of the PI3K/Akt/mTOR pathway. Fisetin treatment of TNF-α-stimulated NHEKs significantly inhibited the activation of p38 and JNK, but had no effect on ERK1/2. In addition, fisetin treatment significantly decreased the secretion of Th1/Th-17 pro-inflammatory cytokines, particularly IFNγ and IL-17A by 12-O- tetradecanolylphorbol 13-acetate (TPA)-stimulated NHEKs and anti-CD3/CD28-activated human PBMCs. Furthermore, we established the in-vivo relevance of fisetin functions, using a 3D full-thickness human skin model of psoriasis (FTRHSP) that closely mimics in-vivo human psoriatic skin-lesions. Herein, fisetin significantly ameliorated psoriasis-like disease features, and decreased the production of IL-17 by CD4+ T lymphocytes co-cultured with FTRHSP. Collectively, our data identify pro-differentiative, anti-proliferative and anti-inflammatory effects of fisetin, via modulation of PI3K-Akt-mTOR and p38/JNK pathways and the production of cytokines in 2D and 3D human skin model of psoriasis. These results suggest that fisetin has a great potential to be developed as an effective and inexpensive agent for the treatment of psoriasis and other related inflammatory skin disorders.