Acute myeloid leukemia (AML) is a malignant disease of the blood and bone marrow that is characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells. Nucleophosmin 1 (NPM1) gene mutations are the most common genetic abnormality in AML, detectable in blast cells from about one third of adults with AML. AML NPM1mut is recognized as a separate entity in the World Health Organization (WHO) classification of AML. Clinical and survival data suggest that patients with this form of AML often have a more favorable prognosis, which may be due to the immunogenicity created by the mutations in the NPM1 protein. Consequently, AML with NPM1mut can be considered an immunogenic subtype of AML. However, the underlying mechanisms of this immunogenicity and associated favorable survival outcomes need to be further investigated. Immune checkpoint molecules, such as the programmed cell death-1 (PD-1) protein and its ligand, PD-L1, play important roles in leukemogenesis through their maintenance of an immunosuppressive tumor microenvironment. Preclinical trials have shown that the use of PD-1/PD-L1 (PDx) checkpoint inhibitors in solid tumors and lymphoma work best in novel therapy combinations. Patients with NPM1mut AML may be better suited to immunogenic strategies that are based on the inhibition of the immune checkpoint pathway of PDx than patients without this mutation, suggesting the genetic landscape of patients may also inform best practice for the use of PDx inhibitors.

This paper investigates the effects of air void topology on hydraulic conductivity in asphalt mixtures with porosity in the range 14%-31%. Virtual asphalt pore networks were generated using the Intersected Stacked Air voids (ISA) method, with its parameters being automatically adjusted by the means of a differential evolution optimisation algorithm, and then 3D printed using transparent resin. Permeability tests were conducted on the resin samples to understand the effects of pore topology on hydraulic conductivity. Moreover, the pore networks generated virtually were compared to real asphalt pore networks captured via X-ray Computed Tomography (CT) scans. The optimised ISA method was able to generate realistic 3D pore networks corresponding to those seen in asphalt mixtures in term of visual, topological, statistical and air void shape properties. It was found that, in the range of porous asphalt materials investigated in this research, the high dispersion in hydraulic conductivity at constant air void content is a function of the average air void diameter. Finally, the relationship between average void diameter and the maximum aggregate size and gradation in porous asphalt materials was investigated.

Placental cadherin (cadherin-P, CDH3) is a cell-to-cell adhesion molecule expressed at a high level in many malignant tumors. Associations of serum CDH3 with atherosclerosis have not been investigated previously. The present clinical cohort study with 3-year follow up measured atherosclerosis of the coronary, brachiocephalic, and femoral circulation and fasting levels of CDH3 in the serum in 218 patients in a hospital setting. Coronary lesions were assessed as Gensini score calculated according to the data of coronary angiography. The volumes of the brachiocephalic and femoral circulation plaques were quantified by ultrasound imaging. Serum proteomic profiling was performed in selected samples using antibody microarrays. The content of CDH3 in the serum was measured using an indirect ELISA. Odds ratio (OR), ROC-analysis, and logistic regressions were used to evaluate the associations between CDH3 content, atherosclerotic lesions, and various serum biomarkers. CDH3 serum content was associated with severity of atherosclerosis and diastolic blood pressure. The levels of СDH3 were able to discriminate patients with total subclinical and hemodynamically significant atherosclerotic lesions in all circulation pools (coronary, brachiocephalic, and femoral). Elevated serum СDH3 appeared to be a risk factor for cardiovascular outcomes after 3-year follow up with OR=1.81 (95%CI: 1.07-3.72; P=0.022). Endothelin-1 and NOx were associated with the content of СDH3 in the serum, suggesting the involvement of certain signal transduction pathways that may participate in plaque formation. CDH3 was associated with cardiovascular outcomes adjusted for coronary plaque presence, indicating a role of CDH3 in plaque biology.

This paper presents a comparison between rain gauges, C-band and X-band radar data over an instrumented and regulated catchment of the Paris region, as well as their respective hydrological impacts with the help of flow observations and a semi-distributed hydrological model. Both radars confirm the high spatial variability of the rainfall down to their space resolution (respectively one kilometer and 250 m) and therefore underscore limitations of semi-distributed simulations. The use of the polarimetric capacity of the Météo-France C-band radar was limited to corrections of the horizontal reflectivity and its rainfall estimates are adjusted with the help of a rain gauge network. On the contrary, neither calibration was performed for the polarimetric X-band radar of the Ecole des Ponts ParisTech (below called ENPC X-band radar), nor any optimization of its scans. In spite of that and the non-negligible fact that the catchment was much closer to the C-band radar than to the X-band radar (20 km vs. 40 km), the latter seems to perform at least as well as the former, but with a higher scale resolution. This characteristic was best highlighted with the help of a multifractal analysis of the respective radar data, which also shows that the X-band radar was able to pick up a few extremes that were smoothed out by the C-band radar.

Understanding the CO2 displacement mechanism in ultra-low permeability reservoirs is essential for improving oil recovery. In this research, a series of displacement experiments were conducted on sandstone core samples from the Chang 6 reservoir in the Huaziping area, using a multifunctional core displacement apparatus and Nuclear Magnetic Resonance (NMR) technology under conditions of constant pressure, variable pressure, and constant effective confining stress. The results revealed that the distribution characteristics of pore structure in the rock samples were critical factors influencing CO2 displacement efficiency. Under the same conditions, cores with more large pores exhibited higher oil recovery. Though fractures can facilitate CO2 flowing through pores, but the confining pressure applied during displacement caused partial closure of fractures, resulting in reduced rock permeability. Based on the oil-to-gas ratio and oil recovery in the outlet section of fractured rock samples, the CO2 displacement process exhibited five stages of no gas，a small amount of gas, gas breakthrough, large gas channeling, and gas fluctuation. Although the displacement stage of different cores is different, it is in the breakthrough stage in the range of 2PV.

Obesity is a chronic disease that is rapidly increasing in prevalence and affects more than 600 million adults worldwide, and this figure is estimated to increase by at least double by 2030. In the United States, more than one-third of the adult population is either overweight or obese. The global obesity epidemic is a major risk factor for the development of life-threatening arrhythmias occurring in patients with long QT, particularly in conditions where multiple heart-rate-corrected QT-interval-prolonging mechanisms are simultaneously present. In obesity, excess dietary fat in adipose tissue stimulates the release of immunomodulatory cytokines such as interleukin (IL)-6, leading to a state of chronic inflammation in patients. Over the last decade, increasing evidence has been found to support IL-6 signaling as a powerful predictor of the severity of heart diseases and increased risk for ventricular arrhythmias. IL-6’s pro-inflammatory effects are mediated via transsignaling and may represent a novel arrhythmogenic risk factor in obese hearts. The first selective inhibitor of IL-6 trans-signaling, olamkicept, has shown encouraging results in phase II clinical studies for inflammatory bowel disease. Nevertheless, the connection between IL-6 trans-signaling and obesity-linked ventricular arrhythmias remains unexplored. Therefore, understanding how IL6 trans-signaling elicits a cellular pro-arrhythmic phenotype and its use as an anti-arrhythmic target in a model of obesity remain unmet clinical needs.

Zn2+ has been implicated in the regulation of intestinal redox and microbial homeostasis, and we recently reported that transient receptor potential canonical (TRPC) 6 channel activity contributes to intracellular Zn2+ homeostasis in mammalian cells. This study aims to investigate the role of TRPC6-mediated Zn2+ influx in stress resistance of intestine. Expression profile of TRPC1-C7 mRNAs in the actively inflamed mucosa from inflammatory bowel disease (IBD) patients was analyzed using GEO database. Systemic TRPC3-knockout (KO) and TRPC6-KO mice were treated with dextran sulphate sodium (DSS) to induce colitis. The Zn2+ concentration and the mRNA expression levels of oxidative/inflammatory markers in colon tissues were quantitatively analyzed, and gut microbiota profiles were compared. TRPC6 mRNA expression level was increased in IBD patients and DSS-treated mouse colon tissues. DSS-treated TRPC6-KO mice, but not TRPC3-KO mice, showed severe weight loss and increased disease activity index compared with DSS-treated WT mice. The mRNA abundances of antioxidant proteins were basically increased in TRPC6-KO colon, with changes in gut microbiota profiles. Treatment with TRPC6 activator prevented the DSS-induced colitis progression accompanied by increasing Zn2+ concentration. We suggest that TRPC6-mediated Zn2+ influx activity plays a key role in stress resistance against IBD, providing a new strategy for treating colitis.

Intracranial and extracranial large artery atherosclerosis (LAA) are a main cause of ischemic stroke. Biomarkers may aid in the diagnosis of LAA and help to stratify patients´ risk of stroke. We performed a narrative review of the literature mainly published in the last five years with the aim of identifying biomarkers associated either with intracranial or extracranial LAA in humans. Several potential biomarkers of LAA mainly related to lipid pathways and inflammation have been studied. Diagnostic biomarkers of LAA were evaluated by measuring biomarkers levels in patients with LAA stroke and other stroke etiologies. Some biomarkers were associated with prognosis of LAA stroke as evaluated by the modified Rankin score. Increased levels of IL-6 and have been associated with the risk of progression of the atherosclerotic disease. Overall, in most studies, the results were not externally validated. External validation of these results is needed. In the future, biomarkers could be useful for the selection of patients for clinical trials. To adopt these biomarkers in clinical practice we will need robust multicentric studies proving their reproduci-bility and a clear practical applicability for their use.

Helicosporous hyphomycetes is a class of filamentous fungi that shows promising application prospects in metabolizing bioactive natural compounds. During a study of helicosporous fungi in China, six new helicosporous taxa were collected and isolated from decaying wood in Guangxi Zhuang Autonomous Region, China. Morphological comparisons with multi-gene phylogenetic analyses revealed that these six taxa belong to Helicosporium (Tubeufiaceae, Tubeufiales), and they can be recognized as three novel species, named Helicosporium liuzhouense, H. multidentatum and H. nanningense. Detailed descriptions and illustrations of the newly discovered taxa and comparisons with similar fungi are provided. In addition, a list and a key to accepted Helicosporium species are provided.

This paper presents the values of several mechanical characteristics for two blends: H (60% PP + 12% PA6 + 8% EPDM + 20% Polybond 3200) and G (20% PP + 42% PA6 + 28% EPDM + 10% Polybond 3200) (%wt), comparing them to those of PP (polypropylene) and PA6 (polyamide 6). The adding of EPDM (ethylene propylene diene monomer rubber) and Polybond 3200 help reducing the disadvantages of simple blends made of PP+PA6, when the PA6 concentration allows for having a PA6 matrix with droplets of PP. SEM analysis helps for understanding the performance of material G as compared to the neat polymers. EDX analysis proved that there was a matrix inversion, material H having a PP matrix and material G a matrix made of PA6 with droplets of PP. Strain at break for PP and material H were proved to be insensitive to test speed, but materials G and PA6 had large value for strain at break and energy at break for v = 10 mm/min. Taking at basis the values for polyamide 6 (PA6), material G has greater values for energy at break: with 97.8% for v = 10 mm/min, with 29.5% for v= 250 mm/min and with 98% for 1000 mm/min, without exhibiting the micro and macro cavitation of PA6. This means that the recipe, the technology and the mechanical characteristics make material G a potential candidate for applications where a low and moderate impact resistant material is required.

Cardiac autonomic neuropathy (CAN) is a severe complication of diabetes mellitus (DM) strongly linked to a nearly five-fold higher risk of cardiovascular mortality. Patients with Type 2 Diabetes Mellitus (T2DM) are a significant cohort in which these assessments have particular relevance to the increased cardiovascular risk inherent in the condition. This study aimed to explore the subtle correlation between the Ewing test, Sudoscan-cardiovascular autonomic neuropathy score, and cardiovascular risk calculated using SCORE 2 Diabetes in individuals with T2DM. The cohort consisted of 211 patients diagnosed with T2DM with overweight or obesity without established ASCVD, aged between 40 to 69 years. The prevalence of CAN in our group was 67.2%. In the study group, according SCORE2-Diabetes, four patients (1.9%) were classified with moderate cardiovascular risk, thirty-five (16.6%) with high risk, and one hundred seventy-two (81.5%) with very high cardiovascular risk. On multiple linear regression, the SCORE2-Diabetes algorithm remained significantly associated with Sudoscan CAN-score and Sudoscan Nephro-score and Ewing test score. Testing for the diagnosis of CAN in very high-risk patients should be performed because approximately 70% of them associate CAN. Increased cardiovascular risk is associated with sudomotor damage and that Sudoscan is an effective and non-invasive measure of identifying such risk.

HIV-1 Tat protein interacts with TAR RNA and recruits CDK9/cyclin T1 and other host factors to induce HIV-1 transcription. Thus Tat-TAR RNA interaction, which is unique for HIV-1, represents an attractive target for anti-HIV-1 therapeutics. To target Tat-TAR RNA interaction, we used a crystal structure of TAR RNA with acetylpromazine bound to the bulge of TAR RNA, to dock compounds from Enamine database containing 1.6 million individual compounds. Docking identified 173 compounds that were analyzed for the inhibition of HIV-1 infection. Top ten inhibitory compounds with IC50 ≤ 6 µM were selected and the three least toxic compounds, T6780107 (IC50=2.97 μM), T0516-4834 (IC50=0.2 μM) and T5628834 (IC50=3.46 μM), were further tested for HIV-1 transcription inhibition. Only T0516-4834 compound showed selective inhibition of Tat-induced HIV-1 transcription, whereas T6780107 compound inhibited equally basal and Tat-induced transcription and T5628834 compound only inhibited basal HIV-1 transcription. The T0516-4834 compound also showed strongest inhibition of HIV-1 gag RNA expression and p24 production in CEM T cells infected with HIV-1 IIIB. Of the three compounds, only the T0516-4834 compound disrupted Tat-TAR RNA interaction indicating that it might target TAR RNA. Also, of the three tested compounds, T5628834 but not T6780107 or T0516-4834 disrupted Tat-CDK9/cyclin T1 interaction. Taken together, our study identified novel compound T0516-4834 that disrupted Tat-TAR RNA interaction and inhibited Tat-induced transcription and HIV-1 infection suggesting that this compound might serve as a new lead for anti-HIV-1 therapeutics.

Prestressed concrete sleepers (or railroad ties) are principally designed in order to carry wheel loads from the rails to the ground of railway tracks. Their design takes into account static and dynamic loading conditions. In spite of the most common use of the prestressed concrete crossties in railway tracks, there have always been many demands from rail engineers to improve serviceability and functionality of concrete crossties. For example, signaling, fiber optic, equipment cables are often damaged either by ballast corners or by tamping machine. There has been a need to re-design concrete crosstie to cater cables internally so that they would not experience detrimental or harsh environments. Also, many concrete crossties need a retrofit for automatic train control device and similar signaling equipment. In contrast, the effects of holes and web openings on structural capacity of concrete crossties have not been thoroughly investigated. This paper accordingly highlights the effect of holes and web openings on the toughness and ductility of concrete crossties. The outcome of this research enables better decision making process for retrofiting prestressed concrete crossties with holes and web opening in practice.

The world is currently going through a serious pandemic of viral infection with SARS-CoV-2, a new isolate of coronavirus, resembling and surpassing the crisis that occurred in 2002 and 2013 with SARS and MERS, respectively. SARS-CoV-2 has currently infected more than 142,000 people, causing 5,000 deaths and reaching more than 130 countries worldwide. The very large spreading capacity of the virus clearly demonstrates the potential threat of respiratory viruses to human health, alarming governments around the world that preventive health policies and scientific research are pivotal to overcoming the crisis. Coronavirus disease 2019 (COVID-19) causes flu-like symptoms in most cases. However, approximately 15% of patients will need hospitalization, and 5% require assisted ventilation, depending on the cohorts studied. What is intriguing, however, is the higher susceptibility of elderly individuals, especially those who are more than 60 years old and have comorbidities, including hypertension, diabetes and heart disease. In fact, the death rate in this group may be up to 10-12%. Interestingly, children are somehow protected and not included as a risk group.Thus, here, we discuss some possibilities of molecular and cellular mechanisms by which elderly subjects may be more susceptible to severe COVID-19. In this sense, we raise two main points: i) increased ACE-2 expression in pulmonary and heart tissue of chronic angiotensin 1 receptor (AT1R) blocker users and hypertensive individuals and ii) antibody-dependent enhancement (ADE) after previous exposure to other circulating coronaviruses. We believe these are pivotal points for a better understanding of the pathogenesis of severe COVID-19 and must be addressed with attention by physicians and scientists in the field.

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

Undernutrition is a significant public health issue in Colombia and globally, influenced by multiple factors. The relationship between food insecurity and acute undernutrition in children has been insufficiently explored. To address this, a descriptive, observational, cross-sectional study was conducted involving 70 children under the age of 5, who presented with moderate to severe acute malnutrition. The study assessed family and child food security using the Latin American and Caribbean Food Security Scale (ELCSA). Analysis of the data revealed that when households face challenges in meeting their basic needs, children are generally the least affected. Caregivers tend to prioritize children's diets, opting to reduce food intake among adults over 18 years of age instead. The causes of malnutrition were explored through the perceptions of guardians, who reported that in 30.2% of cases, malnutrition is linked to inadequate feeding and parenting practices. Specific issues noted by parents included children being too lazy to chew, preferring ultra-processed foods, or refusing to eat altogether. The study found that not all children with acute malnutrition experience food insecurity; in fact, the proportion of children suffering from hunger was very low. The findings suggest that malnutrition in children under 5 years of age is not solely determined by food insecurity but also by other factors such as parenting practices and poor feeding habits. Further research is needed to evaluate food access and quality, particularly in terms of dietary diversity, to better understand the needs of each population. Such studies will be essential in guiding public health interventions aimed at preventing, managing, and addressing malnutrition in children.

In May 2022, WHO reported an outbreak of Mpox in several European countries which were previously Mpox free. Mpox (formerly known as monkeypox) is a zoonotic viral disease endemic in Central and West Africa. The sudden emergence of Mpox outside Africa and its subsequent rapid spread lead the WHO to declare the outbreak as Public Health Emergency of International Concern. As of May 15, 2023, a total of 87,704 confirmed cases and 140 deaths had been reported from 111 countries and territories worldwide. Looking back on this outbreak one year later, several important questions have arisen. Here, we address these questions using the classic five Ws: What, When, Where, Who and Why? We discuss these questions and outline what needs to be done to prevent, or at least minimize, outbreaks from emerging and re-emerging viral infection.

In this work, polyacrylic acid-functionalized MCM-41 was synthesized, which was further interacted with calcium ions, to realize enhanced pH-responsive nanocarrier for sustained drug release. First, mesoporous silica nanoparticles (MSNs) were prepared by the sol-gel method. Afterward, (3-trimethoxysilyl)propyl methacrylate (TMSPM) modified surface was prepared by using the post-grafting method, then polymerization of acrylic acid was proceeded. After adding calcium chloride solution, polyacrylic acid-functionalized MSNs with calcium-carboxyl ionic bonds in the polymeric layer, which can prevent the cargo from leaking out of the mesopore, were prepared. The structure and morphology of the modified nanoparticles (PAA-MSNs) were characterized by X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), and N2 adsorption-desorption analysis, etc. The controlled release of guest molecules was studied by using 5-fluorouracil (5-FU). The drug molecules-incorporated nanoparticles showed different releasing rates under different pH conditions. It is considered that our current materials have the potential as pH-responsive targeted nanocarriers in the field of medical treatment.

Trace amine-associated receptors (TAARs) are a family of G protein-coupled receptors present in mammals in the brain and in several peripheral organs. Apart from its olfactory role, TAAR5 is expressed in the major limbic brain areas and regulates brain serotonin functions and emotional behaviors. However, most of its functions remain undiscovered. Given the role of serotonin and limbic regions in some aspects of cognition, we used a temporal decision-making task to unveil a possible role of TAAR5 in cognitive processes. We found that TAAR5 knock-out (KO) mice showed a generally better performance due to a reduced number of errors and displayed a greater rate of improvement at the task than WT littermates. However, task-related parameters, such as time accuracy and uncertainty have not changed significantly. Overall, we show that TAAR5 modulates specific domains of cognition, highlighting a new role in brain physiology.

Erectile dysfunction (ED) due to diabetes mellitus remains difficult to treat despite advances in pharmacotherapeutic approaches in the field. Therefore, this study investigated the erectogenic effect of the methanolic extract of Maytenus procumbens roots on type 2 diabetes in rats. The fructose-streptozotocin model was used to induce type 2 diabetes-linked ED in male rats. The sexually active male Sprague Dawley rats were randomly divided into two major groups; normal group and high fructose fed group for 120 days. After 120 days, the high fructose fed group rats were given a single intraperitoneal injection of a freshly prepared streptozotocin solution (30 mg/kg). The diabetic ED rats were orally administered with the extract at 250 mg/kg, daily for 28 days. The serum, brain and penile tissues were removed for biochemical analysis and protein expression. Increased testosterone level, mounting frequency, reduced blood glucose level and serum fructosamine content was observed after 28 days of treatment in diabetic rats. Methanolic extract also exhibited an inhibitory effect on arginase, AChE, and ACE activities. The crude extract further downregulated proteins PDE-5, RhoA and increased expression of eNOS in the diabetic ED treated rats. The results obtained indicate that the methanolic extract of Maytenus procumbens roots ameliorates erectile dysfunction in type 2 diabetes-induced erectile dysfunction in rats.

Lung cancer is almost the most common cause of cancer death in the world. Clinically, the conventional therapy to eradicate the cancer cells is chemotherapy but a better drug remains required. In this study, the effects of three bufadienolides, kalantuboside B, kalantuboside A and bryotoxin C, isolated from Kalanchoe tubiflora (Harvey) were evaluated and characterized in CL1-5 highly metastatic human lung cancer cells. Contrary to the apoptosis-promoting activity in other cancer cells, these three bufadienolides did not induce apoptosis in CL1-5 cancer cells. Instead, they activated an autophagy pathway, as indicated by the increase of autophagosomes formation. The induction of autophagy by these three bufadienolides was demonstrated to link to down-regulation of p-mTOR as well as up-regulation of LC3-II, ATG5, ATG7, Beclin-1. Moreover, among these three compounds, kalantuboside B in which a monosaccharide is attached at the bufadienolide aglycon, exhibited a better autophagy induction. Our findings revealed an alternative mechanism of drug action by bufadienolides in lung cancer cells and provided evidence for the possibility of treating highly metastatic human lung cancer through an autophagy pathway.

Staphylococcus aureus and coagulase-negative staphylococci account for about 80% of infections associated with medical devices and are associated with increased virulence due to their ability to form biofilm. In this study, we aimed to construct a comprehensive reference map followed by significant pathway analysis in the proteome of S. aureus biofilm grown for 3-days as compared with 24 h planktonic using a high-resolution TMT based MS. We identified proteins associated with secondary metabolites, ABC transporters, biosynthesis of amino acids, response to stress, and amino sugar and nucleotide sugar metabolism were significantly upregulated in the 3-day biofilm. In contrast, proteins associated with virulence factors, microbial metabolism in diverse environments, translation, and energy metabolism were significantly downregulated. GO functional annotation indicated that more proteins are involved in metabolic processes, catalytic activity, and binding in biofilm, respectively. Among the significantly dysregulated proteins, hyaluronidase (hysA) in conjunction with chitinase may play a significant role in the elimination and/or prevention of biofilm development. This study advances the current S. aureus subproteomes, identified potential pathways significant to biofilm biology and helped to understand their potential role in S. aureus which may shed light on developing new therapeutic regimes including antibiofilm agents in the treatment of biofilm-infections related with implantable medical devices.

Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and an efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even many of them have been proved effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarise the available scientific information on these joint-friendly medicinal plants, which have been already tested in human studies: Arnica montana, Boswelliaspp., Curcuma spp., Equisetum arvense, Harpagophytumprocumbens, Salix spp., Sesamumindicum, Symphytumofficinalis, Zingiberofficinalis, Panaxnotoginseng, Whitaniasomnifera.

Background and Objectives: Stroke is a main leading cause for mortality and morbidity worldwide. Treat-ment of this pathology is still under development and its risk factors remain the main target to be reached. Therefore, we aim to determine the role of interleukin 1 beta in atheromatosis, as risk factor for stroke and the reole of this biomarker in stroke prognosis. Materials and Methods: The study conducted enrolled 56 patients diagnosed with ischemic stroke in the anterior (AVT) and posterior vascular territory (PVT). All patients had venous blood collected at admission and 7 days after the onset of the cerebral ischemia in order to determine plasma concentration for interleukin 1 beta. At the same time an extracranial carotid ultrasound was performed. Results: Interleukin 1 beta collected at admission was positively correlated with NIHSS at admission (Pearson index 0,424) and both measurements were corelated with carotid stenosis (Spearmen correlation index 0,529, respectively 0,653). Conclusion: Interleukin 1 beta could be a reliable biomarker for stroke prognosis and carotid atheromatosis development.

Some glucagon-like peptide-1 receptor agonists (GLP-1 RAs), first used in the treat-ment of type 2 diabetes mellitus (T2DM), have been approved for the treatment of obe-sity in patients with or without T2DM (liraglutide – LIR, semaglutide - SEM, and tir-zepatide - TIR). Social media had an important influence on the off-label use of GLP-1 RAs for obesity, especially for SEM. We analysed the Google queries related to SEM to assess people's interest in this drug. We also investigated the occurrence of adverse drug reactions (ADRs) by searching the EudraVigilance database (EV) for Individual Case Safety Reports (ICSRs) that reported SEM as the suspected drug and performed a descriptive and a disproportionality analysis. Data obtained for SEM were compared to other GLP-1 RAs. SEM had the highest proportions of searches on Google associated with the term “weight loss” and presented the lowest number of severe ADRs, but it also had the highest number of ICSRs reported in EV. Even though no unexpected safety issues have been reported for it until now, SEM has a high tendency for overdose reports. The most frequent off-label use was reported for SEM and TIR. In order to lower the ADRs’ risks, the off-label use should be reduced and carefully monitored.

Background: Fullerenes and metallofullerenes can be considered promising nanopharmaceuticals themselves and as a basis for chemical modification. As reactive oxygen species homeostasis plays a vital role in cells, the study of their effect on genes involved in oxidative stress and anti-inflammatory response is of particular importance. Methods: Human fetal lung fibroblasts were incubated with aqueous dispersions of C60, C70, and Gd@C82 in concentrations of 5 nM and 1.5 µM for 1, 3, 24, and 72 hours. Cell viability, intracellular ROS, NOX4, NFκB, PRAR-γ, NRF2, heme oxygenase 1, and NAD(P)H quinone dehydrogenase 1 expression have been studied. Results & conclusion: The aqueous dispersions of C60, C70, and Gd@C82 fullerenes are active participants in ROS homeostasis. Low and high concentrations of AFDs have similar effects. C70 was the most inert substance, C60 was the most active substance. All AFDs have both a “prooxidant” and “antioxidant” effect, but with a different balance. Gd@C82 was a substance with more pronounced antioxidant and anti-inflammatory properties, while C70 had more pronounced “prooxidant” properties.

Air filtration mechanisms in the composite filter media used in practical applications are important and challenging to understand because the component fibers could have various size scales and morphologies. In this work, a three-dimensional digital model of nanofiber-based filter media was reconstructed for the first time based on the X-ray tomography data for the cellulose substrate and the Focused Ion Beam-Scanning Electron Microscope (FIB-SEM) image analysis for the several microns thick (3.82-7.90 μm) electrospun polyvinylidene fluoride (PVDF) nanofiber membrane. Besides the high-resolution model where the details of the fibrous structures were fully resolved, another low-resolution model with approximated unresolved structures was also established. Filtration simulations utilizing these models were conducted considering the drag force, Brownian diffusion and aerodynamic slip. The simulated filtration efficiencies agreed well with the experiments for particles of 70-400 nm, including the most penetrating particle size (MPPS, 100-200 nm). Moreover, the structure-resolved models had higher accuracy but higher computational costs, while the unresolved simulations saved much running time but over-predicted the filtration efficiency, especially for smaller particles (<100 nm). Our study presents a comprehensive strategy for investigating the composite filter media with multiscale complex structures using a combination of advanced characterization technologies and modular simulation models.

The copolyester of 3-hydroxybutyrate (3HB) and 3-hydoxyhexanoate (3HHx), PHBHHx, is a bi-odegradable plastic that has a high flexibility, softness, wide process window and marine bio-degradability. PHBHHx is usually produced from structurally related carbon sources such as vegetable oils or fatty acids but not from inexpensive carbon sources like sugars. In the previous studies, we demonstrated that engineered strains of hydrogen-oxidizing bacterium, Cupriavidus necator synthesized PHBHHx with high cellular content from not only sugars but also from CO2 as the sole carbon source in the flask culture. In this study, highly efficient production of PHBHHx from CO2 was investigated by pH-stat jar cultivation of the recombinant C. necator strains with feeding the substrate gas mixture (H2/O2/CO2=8:1:1) to complete mineral medium in recycled-gas closed-circuit culture system. As the result with the strain MF01/pBPP-ccrMeJAc-emd, the dry cell mass and PHBHHx concentration reached up to 59.62 ± 3.18 g･L-1 and 49.31 ± 3.14 g･L-1, respectively after 212 h of jar cultivation with limited addition of ammonia and phosphate solutions. The 3HHx composition was close to 10 mol% which is suitable for practical applica-tions. It is expected that autotrophic cultivation of the recombinant C. necator can be a feasible process for mass production of PHBHHx from CO2.

Lung cancer (LC) is the second most common cancer and the leading cause of cancer deaths in the U.S. Insulin therapy, a key treatment for managing Type 2 Diabetes Mellitus (T2DM), may increase LC risk. The impact of non-insulin antidiabetic drugs, particularly GLP-1 receptor agonists (GLP-1RAs), on LC risk is not well understood. This study evaluated LC risk in T2DM patients comparing seven non-insulin antidiabetic agents to insulin. Using the TriNetX Analytics platform, we analyzed de-identified electronic health records of 1,040,341 T2DM patients treated between 2005-2019, excluding those with prior antidiabetic use or LC diagnoses. We calculated hazard ratios and confidence intervals for LC risk and used propensity score matching to control for confounding factors. All non-insulin antidiabetic drugs, except alpha-glucosidase inhibitors, significantly reduced LC risk compared to insulin, with GLP-1RAs showing the greatest reduction (HR: 0.49, 95% CI: 0.41, 0.59). GLP-1RAs were consistently associated with lowered LC risk across all histological types, races, genders, and smoking statuses. These findings suggest that non-insulin antidiabetic drugs, particularly GLP-1RAs, may be preferable for managing T2DM while reducing LC risk.

Adverse medical events not only harm patients and families, but also cause significant negative impact on healthcare providers, with potential to compromise future professional functioning. These “second victims” may need organizational support and rehabilitation to return to functionality. We analyzed the validity of an adapted tool, the Second Victim Experience and Support Tool (SVEST), to a population in Israel, H-SVEST. The H-SVEST was completed by 172 nurse participants working in a variety of patient care settings. The H-SVEST was assessed for content validity, internal consistency, and construct validity with confirmatory factor analysis (CFA). The CFA run on the initial model with 10 factors and 36 items did not meet criteria for goodness of fit. After removing five items based on their low factor loadings and the correlation, The model fit significantly improved with acceptable CFI, TLI, RMSEA, and SRMR; χ2(389) =626.939, p<.001; χ2/df=1.61; TLI=0.901; CFI=0.917; RMSEA [90% CI]=0.060 [0.051, 0.068]; SRMR=0.064. The final version included 31 items and 10 factors with Cronbach α values ranging from 0.66 to 0.94. The H-SVEST demonstrates robust psychometric properties and valuable insights into the second victim experience in the Israeli context. Comparative analysis with other versions highlights potential cultural influences and areas for further investigation. Implementing this tool and developing evidence-based interventions based on its results can significantly improve well-being and resilience of healthcare providers in Israel and other countries with diverse cultural populations. This study was not registered.

A typical vibrational spectrum in the ice phase has four separate bands: translation, libration, bending and stretching. Ice X, the final ice phase under high pressure, shows an exotic vibrational spectrum. Theoretically, an ideal crystal of ice X only has one peak at 998 cm-1 for Raman scattering and two peaks at 450 cm-1 and 1507 cm-1 for infrared absorption in this work. These three characteristic peaks are indicators of the phase transition between ice VII/VIII and ice X. Despite much experimental and theoretical work on ice X, only this study has clearly indicated these characteristic peaks in the region of the IR band. The phonon density of states shows quite different features than ice VIII, which could be verified by inelastic neutron scattering in the future. The dynamic processes of 15 vibrational normal modes are discussed and the typical hydrogen bonds are missing.

In this research, new setting is introduced for new SuperHyperNotions, namely, an 1-failed SuperHyperForcing and Neutrosophic 1-failed SuperHyperForcing. Assume a SuperHyperGraph. Then an ``1-failed SuperHyperForcing'' $\mathcal{Z}(NSHG)$ for a neutrosophic SuperHyperGraph $NSHG:(V,E)$ is the maximum cardinality of a SuperHyperSet $S$ of black SuperHyperVertices (whereas SuperHyperVertices in $V(G) \setminus S$ are colored white) such that $V(G)$ isn't turned black after finitely many applications of ``the color-change rule'': a white SuperHyperVertex is converted to a black SuperHyperVertex if it is the only white SuperHyperNeighbor of a black SuperHyperVertex. The additional condition is referred by ``1-'' about the usage of any black SuperHyperVertex only once to act on white SuperHyperVertex to be black SuperHyperVertex; a ``neutrosophic 1-failed SuperHyperForcing'' $\mathcal{Z}_n(NSHG)$ for a neutrosophic SuperHyperGraph $NSHG:(V,E)$ is the maximum neutrosophic cardinality of a SuperHyperSet $S$ of black SuperHyperVertices (whereas SuperHyperVertices in $V(G) \setminus S$ are colored white) such that $V(G)$ isn't turned black after finitely many applications of ``the color-change rule'': a white SuperHyperVertex is converted to a black SuperHyperVertex if it is the only white SuperHyperNeighbor of a black SuperHyperVertex. The additional condition is referred by ``1-'' about the usage of any black SuperHyperVertex only once to act on white SuperHyperVertex to be black SuperHyperVertex. Assume a SuperHyperGraph. Then an ``$\delta-$1-failed SuperHyperForcing'' is a \underline{maximal} 1-failed SuperHyperForcing of SuperHyperVertices with \underline{maximum} cardinality such that either of the following expressions hold for the (neutrosophic) cardinalities of SuperHyperNeighbors of $s\in S:$ $~|S\cap N(s)| > |S\cap (V\setminus N(s))|+\delta,~|S\cap N(s)| < |S\cap (V\setminus N(s))|+\delta.$ The first Expression, holds if $S$ is an ``$\delta-$SuperHyperOffensive''. And the second Expression, holds if $S$ is an ``$\delta-$SuperHyperDefensive''; a``neutrosophic $\delta-$1-failed SuperHyperForcing'' is a \underline{maximal} neutrosophic 1-failed SuperHyperForcing of SuperHyperVertices with \underline{maximum} neutrosophic cardinality such that either of the following expressions hold for the neutrosophic cardinalities of SuperHyperNeighbors of $s\in S:$ $~|S\cap N(s)|_{neutrosophic} > |S\cap (V\setminus N(s))|_{neutrosophic}+\delta,~ |S\cap N(s)|_{neutrosophic} < |S\cap (V\setminus N(s))|_{neutrosophic}+\delta.$ The first Expression, holds if $S$ is a ``neutrosophic $\delta-$SuperHyperOffensive''. And the second Expression, holds if $S$ is a ``neutrosophic $\delta-$SuperHyperDefensive''. A basic familiarity with SuperHyperGraph theory and neutrosophic SuperHyperGraph theory are proposed.

Our study focused on investigating the impact of Instagram use on body satisfaction and self-esteem among participants aged 20 to 40 years (N = 95) through a cross-sectional survey design in which the Rosenberg Self-Esteem Scale, the Body Shape Questionnaire (BSQ), and ad hoc designed questions were administered. The results highlight the influence of Instagram on body dissatisfaction (p = .005) but not on self-esteem (p = .211). Gender was not found to be an influential factor (p = .173). However, it was found that greater body satisfaction correlates with higher self-esteem and vice versa (p < .001). Finally, we concluded that the number of hours users in the sample spend on Instagram is related to greater body dissatisfaction but not to lower self-esteem.

We report on recent experimental results on β decay into self-conjugate (N=Z) nuclei with mass number 58≤A≤70. Super-allowed β decays from the Jπ=0+ ground state of a Z=N+2 parent nucleus are to the isobaric analogue state, through so-called Fermi transitions, and to Jπ=1+ states, by way of Gamow–Teller (GT) transitions. The operator of the latter decay is a generator of Wigner’s SU(4) algebra and as a consequence GT transitions obey selection rules associated with this symmetry. Since SU(4) is progressively broken with increasing A, mainly as a consequence of the spin–orbit interaction, this symmetry is not relevant for the nuclei considered here. We argue, however, that the pseudo-spin–orbit splitting can be small in nuclei with 58≤A≤70, in which case nuclear states exhibit an approximate pseudo-SU(4) symmetry. To test this conjecture, GT decay strength is calculated with use of a schematic Hamiltonian with pseudo-SU(4) symmetry. Some generic features of the GT β decay due to pseudo-SU(4) symmetry are pointed out. The experimentally observed GT strength indicates a restoration of pseudo-SU(4) symmetry for A=70.

This article introduces a new method for modelling and verifying the execution of timed security protocols (TSP) and their time-dependent security properties. The method, which is both novel and reliable, uses an extension of interpreted systems, accessible semantics in multi-agent systems, and timed interpreted systems (TIS) with dense time semantics to model TSP executions. We enhance the models of TSPs by incorporating delays and varying lifetimes to capture real-life aspects of protocol executions. To illustrate the method, we model a timed version of the Needham-Schroeder Public Key Authentication Protocol. We have also developed a new SMT-based bounded model checking reachability algorithm for the proposed structures and implemented it with the tool. The method comprises a new procedure for modelling TSP executions, a translation of TSP into TIS, and a translation of TIS's reachability problem into the SMT problem. The paper also includes thorough experimental results for nine protocols modelled by TIS and discusses the findings in detail.

Conventional monitoring relies on "in vivo" (non-destructive) measurements of aboveground organ traits (such as stems, branches, and leaves) to analyze plantation growth trends and assess the effectiveness of management practices like watering and fertilization. This study reveals the necessity of “ex vivo” (destructive) approaches, post-excavation, to ensure fully reliable monitoring of plantation performance, including belowground organ growth and development trends. We showcase the effectiveness of dendrometric analysis, which measures the annual ring width in the secondary xylem (wood) of the taproot and stem. Monitoring above- and belowground organ growth trends allow for the exploration of similarities and differences in how different tree organs respond to internal and external factors. Such monitoring is especially crucial for assessing plantation performance in challenging climates, such as those found in arid and semi-arid lands.

Diabetes mellitus (DM) poses a significant challenge to global health, with its prevalence projected to rise dramatically by 2045. This narrative review explores the bidirectional relationship between periodontitis (PD) and type 1 diabetes mellitus (T1DM), focusing on cellular and molecular mechanisms derived by the interplay between oral microbiota and the host immune response. A comprehensive search of literature published between 2008 and 2023 was conducted to elucidate the association between these two diseases. Preclinical and clinical evidence suggests a bidirectional relationship, with individuals with T1DM exhibiting heightened susceptibility to periodontitis, and vice versa. The review includes recent findings from human clinical studies, revealing variations in oral microbiota composition in T1DM patients, including increases in certain pathogenic species such as Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, along with shifts in microbial diversity and abundance. Molecular mechanisms underlying this association involve oxidative stress and dysregulated host immune responses, mediated by inflammatory cytokines such as IL-6, IL-8, and MMPs. Furthermore, disruptions in bone turnover markers, such as RANKL and OPG, contribute to periodontal complications in T1DM patients. While preventive measures to manage periodontal complications in T1DM patients may improve overall health outcomes, further research is needed to understand the intricate interactions between oral microbiota, host response, periodontal disease, and systemic health in this population.

The processes of the sublimation and thermal decomposition of the 1‐ethyl‐3‐methylimidazolium hexafluorophosphate ionic liquid (EMImPF6) were studied by a complex approach including Knudsen effusion mass spectrometry, IR and NMR spectroscopy, and quantum chemical calculations. It was established that the vapor over liquid phase primarily consists of decomposition products under equilibrium conditions. Otherwise, the neutral ion pairs are the only vapor components under Langmuir conditions. To identify the nature of the decomposition products an experiment on the distillation of the ionic liquid was performed and the collected distillate was analyzed. It was revealed by the IR and NMR spectroscopy that EMImPF6 decomposes to substituted imidazole‐2‐ylidene (C6N2H10PF5) and HF. The measured vapor pressure of C6N2H10PF5 reveals a very low activity of the decomposition products (&lt;10–4) in the liquid phase. The absence of significant accumulation of decomposition products in the condensed phase makes it possible to determine the enthalpy of sublimation of the ionic liquid assuming its unchanged activity. The thermodynamics of the EMImPF6 sublimation was studied by Knudsen effusion mass spectrometry. The formation enthalpy of EMImPF6 in ideal gas state was found from combination of the sublimation enthalpy and formation enthalpy of ionic liquid in the condensed state. The obtained value is in good agreement with those calculated by quantum chemical methods.

Multinuclear NMR studies of the gaseous mixtures that involve volatile compounds and ³He atoms are featured in this review. Precise analyses of the ³He and other nuclei resonance frequencies show linear dependences on the gas density. Extrapolation of the gas phase results to the zero-pressure limit gives ν₀(³He) and ν₀(ⁿX) resonance frequencies of nuclei in a single 3-helium atom and nuclei in molecules at a given temperature. The NMR frequency comparison method provides an approach for determining different nuclear magnetic moments. Application of quantum chemical shielding calculations which include a more complete and careful theoretical treatment allows the shielding of isolated molecules to be achieved with great accuracy and precision. They are used for evaluation of nuclear moments without shielding impact on bare nuclei: ^10/11B, ¹³C, ¹⁴N, ¹⁷O, ¹⁹F, ²¹Ne, ²⁹Si, ³¹P, ³³S, ^35/37Cl, ³³S , ⁸³Kr, ^129/131Xe, and ¹⁸³W. On the other hand, new results of nuclear moments were used for reevaluation of absolute nuclear magnetic shielding in molecules under study. Additionally, ³He gas in water solutions of lithium and sodium salts was used for measurements of ^6/7Li and ²³Na magnetic moments and reevaluation of shielding parameters of Li⁺ and Na⁺ water solvated cations. In this paper, guest ³He atoms that play a role in probing the electron density in many host macromolecules are presented as well.

In this work antiparasitic peptidomimetics inhibitors (PEP) of falcipain-3 (FP3) of Plasmodium falciparum (Pf) have been proposed using structure-based and computer-aided molecular design. Beginning with the crystal structure of PfFP3-K11017 complex (PDB ID: 3BWK), three-dimensional (3D) models of FP3-PEPx complexes with known activities (IC50exp) were prepared by in situ modification, based on molecular mechanics and implicit solvation to compute Gibbs free energies (GFE) of inhibitor-FP3 complex formation. This resulted in a quantitative structure-activity relationships (QSAR) model based on a linear correlation between computed GFE (ΔΔGcomp) and the experimentally measured IC50exp: (pIC50exp=-(IC50exp/109) =-0.4517×∆∆Gcomp+4.0865 ; R2 = 0.89). Apart from the structure-based relationship, a ligand-based quantitative pharmacophore model (PH4) of novel PEP analogs where substitutions were directed by comparative analysis of the active site interactions was derived using the proposed bound conformations of the PEPx. This provided structural information useful for the design of virtual combinatorial libraries (VL), which was virtually screened based on the 3D-QSAR PH4. The end results were predictory inhibitory activities falling within the low nanomolar concentration range.

This document describes the theoretical basis of the algorithms used to determine properties of snow and ice from the measurements of the Ocean and Land Color Instrument (OLCI) onboard Sentinel-3 satellites within the Pre-operational Sentinel-3 snow and ice products (SICE) project: http://snow.geus.dk/. The code used for the SICE retrieval and its documentation can be found at https://github.com/GEUS-SICE/pySICE. The algorithms were developed after the work from Kokhanovsky et al. (2018, 2019, 2020).

The energy yield of the Vehicle-integrated photovoltaic (VIPV) differs from that of the standard photovoltaics (PV). It is mainly by the difference of the solar irradiance onto the car-roof and car-bodies as well as its curved-shape. Both meaningful and practical modeling and measurement of the solar irradiance for VIPV are needed to be newly established, not the extension of the current technologies. The solar irradiance was modeled by a random distribution of the shading objects and car-orientation with the correction of the curved surface of the PV modules. The measurement of the solar irradiance onto the car-roof and car-body was done using five pyranometers in five local axes on the car for one year. The measured dynamic solar irradiance onto the car-body and car-roof was used for validation of the solar irradiance model in the car.

The Sentinel Application Platform (SNAP) architecture facilitates Earth Observation data processing (http://step.esa.int/main/toolboxes/snap/). In this work we present results from a new Snow Processor for SNAP. We also describe physical principles behind the developed snow property retrieval technique based on the analysis of Ocean and Land Colour Instrument (OLCI) onboard Sentinel-3A/B measurements over clean and polluted snow fields. Using OLCI spectral reflectance measurements in the range 400-1020nm, we derive important snow properties such as spectral and broadband albedo, snow specific surface area, snow extent and grain size on the spatial grid of 300m. The algorithm also incorporates cloud screening and atmospheric correction procedures over snow surfaces. We present validation results using ground measurements from Antarctica, the Greenland ice sheet and the French Alps. We find the spectral albedo retrieved with accuracy of better than 3% on average, making our retrievals sufficient for a variety of applications. Broadband albedo is retrieved with the average accuracy of about 5% over snow. Therefore, the uncertainties of satellite retrievals are close to experimental errors of ground measurements. The retrieved surface grain size shows good agreement with ground observations. Snow specific surface area observations are also consistent with our OLCI retrievals. We present snow albedo and grain size mapping over the inland ice sheet of Greenland for areas including dry snow, melted/melting snow and impurity rich bare ice. The algorithm can be applied to OLCI Sentinel-3 measurements providing an opportunity for creation of long – term snow property records essential for climate monitoring and data assimilation studies - especially in the Arctic region, where we face rapid environmental changes including reduction of snow/ice extent and, therefore, planetary albedo.

Objective: Lipids are secreted into milk as bilayer-coated structures: milk lipid globules (MLGs). Adipophilin (ADRP) and perilipin 3 (TIP47) are associated with MLGs in human breast milk; however, the role of these proteins in milk lipid secretion is not fully understood. The aim of the study was to investigate levels of ADRP, TIP47 and total lipid content in human breast milk, their mutual correlations and dynamics during lactation. Research Methods & Procedures: Milk samples from 22 healthy lactating women (Caucasian, Central European) were collected at five time points during lactation (1–3, 12–14, 29–30, 88–90 and 178–180 days postpartum). Mass spectrometry-based method was used for quantification of ADRP and TIP47 in the samples. The gravimetric method was used to determine milk total lipid content. Results: We observed distinctive trends in ADRP, TIP47 levels and lipid content in human breast milk during the first 6 months of lactation. We also found a significant association between lipid content and ADRP, lipid content and TIP47, and ADRP and TIP47 concentrations in breast milk at all sampling points. Moreover, we derived an equation for estimating the mean lipid content of milk based on ADRP concentration in human breast milk. Conclusions: A mass spectrometry-based method was developed for quantifying ADRP and TIP47 in human breast milk. Strong mutual correlations were found between ADRP, TIP47 and total lipid content in human breast milk.

In this present study, 3-pentadecyl-phenol was selected as a modifier to prepare a foamable phenolic resin with excellent performance, which was successfully prepared by in-situ modification. Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (¹H NMR, ¹³C-NMR) were used to test and characterize the molecular structure of the modified resin. The results showed that 3-pentadecyl-phenol successfully modified the molecular structure of phenolic resin with a reduction in resin gel time. The effect of changing the added amount of 3-pentadecyl-phenol on the mechanical properties, microstructure and flame retardancy of the modified foam was investigated. The results showed that when the amount of added 3-pentadecyl-phenol was 15% of the total amount of phenol, this resulted in the best toughness of the modified foam, which could be increased to 300% compared to the bending deflection of the unmodified phenolic foam. The cell structure showed that the modified phenolic foam formed a more regular and dense network structure and the closed cell ratio was high. Furthermore, the compressive strength, bending strength, and limited oxygen index were improved, while the water absorption rate was lowered. However, the foam density could be kept below 40 mg/cm³, which does not affect the load.

This paper presents a novel 3-degrees-of-freedom (3-DOF) haptic master with rubber bands for self-resetting. The mechanical design avoids coupling between three directions mechanically by using three perpendicular axis intersecting at one point. Bevel gear transmission is adopted to increase the compactness of the overall structure. VR-based interactive system is designed and built by incorporating the proposed haptic master. The proposed haptic device can generate force feedback along 3-degree-of-freedom motion using motors and provide command signals to the avatar in the virtual environment. In order to analyze the performance of the developed device in terms of haptic feedback operation, ergonomics assessments are designed and experimentally implemented. Preliminary studies on the influencing factor including the guidance force, the reset force, the speed of the avatar and the arm the length have been conducted. The results of this paper are of great significance for the design of the haptic master and interactive system.

Relationship between the results of penile duplex doppler ultrasound (PDDU) and response to vardenafil was investigated in patients diagnosed with erectile dysfunction (ED). Data of 148 patients with ED were analysed retrospectively. Patients who did not respond to therapy were classified as Group I (n = 32), those responded partially were classified as Group II (n = 40) and complete responders were classified as Group III (n = 76). Age, comorbid diseases, vascular and penile pathology were compared among the three groups. While diabetes mellitus (DM) and dyslipedimia positivity adversely affect the response to treatment, the presence of hypertension (HT), peyronie's disease and priapism increase the therapeutic response to the treatment (p < 0.05). Arterial insufficiency was present in 20(30.3%), 25(37,9%) and 21(31.8%) of the patients in Group I, Group II and Group III, respectively (p = 0.001). Venous insufficiency was observed in 3(14.3%) patients in Group I and in 8(85.7%) patients in Group III (p = 0.001). Arterial/venous insufficiency was seen in 9(30%), 14(46.7%) and 7(23.3%) of the patients in Group I, Group II and Group III, respectively (p = 0.001). Response rate to treatment was highest in normal patients according to PDDU, followed by patients with venous insuffiency. Besides, it was found that DM decreased the response to treatment, whereas response was increased in cases with HT, priapism and Peyronie’s disease.

Magneto-optic surface plasmon resonance (MOSPR) based sensors are highly attractive as next generation biosensors. However, these sensors suffer from oxidation leading to degradation of performance, reproducibility of the sensor surface because of the difficulty of removing adsorbed materials, and degradation of sensor surface during surface cleaning, and these limit their applications. In this paper, I propose MOSPR-based biosensors with 0 to 15 nm thick inert polycarbonate laminate plastic as a protective layer and theoretically demonstrate the practicability of our approach in water-medium for three different probing samples: ethanol, propanol, and pentanol. I also investigate microstructure and magnetic properties. The chemical composition and layered information of the sensor are investigated using X-ray reflectivity and X-ray diffraction analyses and these show distinct fcc-Au (111) phases, as dominated by the higher density of conduction electrons in Au as compared to Co. The magnetic characterization measured with the in-plane magnetic field to the sensor surface for both the as-deposited and annealed multilayers showed isotropic easy axis magnetization parallel to the multilayer interface at a saturating magnetic field of <100 Oe. The sensor showed a maximum sensitivity of 5.5 × 10⁴%/RIU for water-ethanol media and the highest detection level of 2.5 × 10⁻⁸ for water-pentanol media as the protective layer is increased from 0 to 15 nm.c

Background & Aims: This RCT aimed to investigate the safety and efficacy of MF4637, a medical food comprising highly concentrated, highly purified, long chain (LC) omega-3 fatty acids, (460 mg eicosapentaenoic acid (EPA) and 380 mg docosahexaenoic acid (DHA)) in correcting the omega-3 fatty acid nutritional deficiency present in non-alcoholic fatty liver disease (NAFLD). The potential for MF4637 to reduce liver fat was evaluated in a subset of patients. Methods: 176 subjects with NAFLD were randomised to receive 3 g/d of LC-omega-3 fatty acids (n=87) or placebo (olive oil; n=89) for 24 weeks, in addition to following standard-of-care dietary guidelines for these patients. Thus, interventions were given on top of the dietary advice. The omega-3 index, omega-6:omega-3 fatty acid ratio (primary outcome) and quantitative measurements of red blood cell (RBC) EPA and DHA (secondary outcome) were determined at baseline and study completion. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) assessment of change in liver fat fraction was conducted in a subset of patients. Results: Of the 176 randomised subjects, 167 were analysed for the primary and secondary outcomes (n=81 in the MF4637 group; n=86 in the placebo group). Supplementation with MF4637 for 24 weeks significantly increased the omega-3 index and absolute values of RBC EPA and DHA, and decreased the omega-6:omega-3 fatty acid ratio in NAFLD patients compared to placebo (p<0.0001). There was a statistically significant reduction in liver fat content within both groups with no difference between them. An inverse relationship between change in absolute RBC EPA+DHA and change in liver fat, AST and ALT levels was seen suggesting that a greater increase in omega-3 content was associated with a reduction for both liver fat content and improvement in liver enzyme levels. Additionally, a significant liver fat-lowering effect of MF4637 compared to placebo was demonstrated in a subset of patients with baseline fatty liver index (FLI) score ≥ 40. There were no serious adverse events related to study interventions. Conclusions: The study results demonstrate that the medical food MF4637, was able to correct the nutritional deficiency of omega-3 in NAFLD patients above and beyond that obtained with nutritional counselling. This demonstrates that MF4637 is beneficial in raising the low omega-3 index observed in these patients. A reduction in hepatic steatosis was demonstrated with both intervention groups although no distinction between groups was seen. Further analyses demonstrate the potential to identify omega-3 sensitive patients using an easily available clinical tool for steatosis prediction.

Fucoidans, known for their diverse biological properties such as anti-inflammatory, antiviral, antitumor, and immune-stimulatory effects, have recently gained attention for their potential benefits in exercise endurance, muscle mass, and anti-fatigue. However, the mechanisms by which fucoidans enhance exercise performance are still unclear. To investigate these effects, we administered 400 mg/kg/day of fucoidan extract derived from Undaria pinnatifida to sixty-four C57BL/6J mice over ten weeks. We evaluated changes in running activity, mitochondrial-related gene expression in skeletal muscle, and alterations in the intestinal microbiome. Our results showed that fucoidan supplementation significantly increased daily running distance and muscle mass by 25.5% and 10.4%, respectively, in mice on a standard chow diet, and with more modest effects observed in those on a high-fat diet (HFD). Additionally, fucoidan supplementation led to a significant increase in beneficial gut bacteria, including Bacteroides/Prevotella, Akkermansia muciniphila, and Lactobacillus, along with a notable reduction in the Firmicutes/Bacteroidetes ratio, indicating improved gut microbiome health. Mechanistically, fucoidan supplementation upregulated the mRNA expression of key genes related to mitochondrial biogenesis and oxidative capacity, such as COX4, MYH1, PGC-1α, PPAR-γ, and IGF1, in both standard chow and HFD-fed mice. Our findings suggest that fucoidan supplementation enhances exercise performance, improves muscle function, and positively modulates the gut microbiome in mice, regardless of diet. These effects may be attributed to fucoidans' potential prebiotic role, promoting the abundance of beneficial gut bacteria and contributing to enhanced exercise performance, increased muscle strength, and improved recovery.

We previously reported a novel secondary progressive multiple sclerosis (SPMS) model, progressive experimental autoimmune encephalomyelitis (pEAE), in oligodendroglia-specific Cx47-inducible conditional knockout (Cx47 icKO) mice. Based on our prior study showing the efficacy of iguratimod (IGU), an anti-rheumatic drug, for acute EAE treatment, we aimed to elucidate the effect of IGU on the SPMS animal model. We induced pEAE by immunizing Cx47 icKO mice with myelin oligodendrocyte glycoprotein peptide 35–55. IGU was orally administered from 17 to 50 days postimmunization. We also prepared primary mixed glial cell culture and measured cytokine levels in the culture supernatant after stimulation with designated cytokines (IL-1α, C1q, TNF-α) and lipopolysaccharide. A migration assay was performed to evaluate the effect of IGU on the migration ability of T cells toward mixed glial cell cultures. IGU treatment ameliorated the clinical signs of pEAE, decreased the demyelinated area, and attenuated glial inflammation on immunohistochemical analysis. Additionally, IGU decreased the intrathecal IL-6 level and infiltrating Th17 cells. The migration assay revealed reduced Th17 cell migration and IL-6 levels in the culture supernatant after IGU treatment. Collectively, IGU successfully mitigated the clinical signs of pEAE by suppressing Th17 migration through inhibition of IL-6 production by proinflammatory-activated glial cells.

Education and heritage are fundamental to achieving sustainable development goals. Integrating heritage into education is crucial for cultivating children's connection to heritage and promoting sustainable development. However, the lack of a scientific framework to guide educational goals across age groups results in unclear integration. This study aims to develop a framework for cultural identity enlightenment within heritage education by conducting literature research and validating it through field observations in kindergartens. It identifies cognitive, emotional and behavioral dimensions, outlining the developmental trajectory of these goals. This framework illustrates how children's understanding progresses from direct experiences to deeper appreciation and creative involvement. It provides teachers with a tool to set goals that empower children as agents, fostering the emergence of cultural awareness and identity. This approach not only enhances cultural identity but also supports sustainable development by advancing the transmission and innovation of cultural heritage.

Objective: Obstructive sleep apnea syndrome (OSAS) is a common sleep disorder that is caused by the reduction or cessation of airflow in the upper airway. Irisin, retinol-binding protein-4 (RBP-4), and adiponectin are the three significant factors in the metabolic process of the human body. The objective of this study was to investigate whether plasma irisin, RBP-4, and adiponectin levels are associated with the severity of OSAS. Methods: According to inclusion and exclusion criteria, 125 patients with OSAS and 46 healthy, gender matched controls were included to the study. The patients were classified according to the apnea hypopnea index (AHI) as 14 mild cases (5<AHI<15), 23 moderate OSAS cases (15<AHI<30) and 88 severe OSAS cases (AHI>30). The plasma irisin, RBP-4 and adiponectin levels were measured and compared between groups. Results: RBP-4 levels were higher in severe OSAS compared to moderate (p<0.05) and mild (p<0.001) OSAS groups, irisin levels were significantly lower compared to moderate (p<0.05) and mild (p<0.001) OSAS groups. There was a negative correlation between irisin and RBP-4 (r=-0.379; p<0.001) and AHI (r=-0.834; p<0.001) and a positive correlation with minimum oxygen saturation (MOS) (r=0.341; p<0.001) in the patient group. In the patient group, there was a negative correlation between adiponectin and BMI (r=-0.682; p<0.001), RBP-4 (r=-0.292; p<0.01) and AHI (r=-0.179; p<0.05) and a positive correlation with MOS (r=0.397; p<0.001). In the patient group, there was a positive correlation between RBP-4 and BMI (r=0.406; p<0.001) and AHI (r=0.473; p<0.001) and a negative correlation with MOS (r=-0.805; p<0.001). As a predictor of OSAS, adiponectin showed the highest specificity (84.8%) and RBP-4 the highest sensitivity (92.0%). Conclusion: The results of the present study demonstrated that the severity of OSAS causes more metabolic problems, including decreased plasma irisin and adiponectin levels and an increased plasma RBP-4 level. As a result, patients with an AHI score greater than thirty should be closely monitored for metabolic and cardiovascular abnormalities.

Gram-negative bacterial infections pose a significant threat to public health. Toll-like receptor 4 (TLR4) recognizes bacterial lipopolysaccharide (LPS) and induces innate immune responses, autophagy and cell death, which have major impacts on the body physiological homeostasis. However, the role of TLR4 in bacterial LPS-induced autophagy and apoptosis in large mammals remains unknown, which are closer to humans than rodents in many physiological characteristics. So far, few reports focus on the relationship between TLR, autophagy and apoptosis in large mammal levels. We urgently need more tools to further explore their crosstalk. Here, we generated a TLR4-enriched mammal model (sheep) and found that a high-dose LPS treatment blocked autophagic degradation and caused strong innate immune responses and severe apoptosis in PBMCs of transgenic offspring. Excessive accumulation of autophagosomes/autolysosomes might contribute to LPS-induced apoptosis in PBMCs of transgenic animals. Further study demonstrated that inhibiting TLR4 downstream NF-κB or p38 MAPK signaling pathways reversed the LPS-induced autophagy activity and apoptosis. These results indicate that the elevated TLR4 aggravates LPS-induced PBMCs apoptosis by leading to lysosomal dysfunction and impaired autophagic flux, which is associated with TLR4 downstream NF-κB and MAPK signaling pathways. This study provides a novel TLR4-enriched mammal model to study its potential effects on autophagy activity, inflammation, oxidative stress and cell death. These findings also enriched the biological functions of TLR4 and provided powerful evidence for bacterial infection.

Chest X-ray (CXR) is the first tool globally employed to detect cardiopulmonary pathologies. These acquisitions are highly affected by scattered photons due to the large field-of-view required. Scatter in CXRs introduces background in the images, which reduces their contrast. We developed three deep learning-based models to estimate and correct the scatter contribution to CXRs. We used a Monte Carlo (MC) ray-tracing model to simulate CXRs from human models obtained from CT scans using different configurations (depending on the availability of dual-energy acquisitions). The simulated CXRs contained the separated contribution of direct and scattered X-rays in the detector. These simulated datasets were then used as the reference for the supervised training of several NN. Three NN models (single and dual energy) were trained with the MultiResUNet architecture. The performance of the NN models was evaluated on CXRs obtained with the MC code from chest CTs of patients affected by COVID-19. The results showed that the NN models were able to estimate and correct the scatter contribution to CXRs with an error &lt;5%, being robust to variations in the simulation setup and improving the contrast in soft tissue. The single-energy model was tested with real CXRs, providing robust estimations of the scatter-corrected CXRs.

Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The antidiabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of antiapoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.

This study investigated the factors affecting consumers’ acceptance to use cashless payment services in Malaysia through the construction of the Cashless Society Acceptance (CSA) model. The Technology Readiness Index 2.0 and Unified Theory of Acceptance and Use of Technology 2 were employed to create the CSA model. A total of 434 questionnaires were collected from Malaysian consumers, aged 18 years and above. The results show that Perceived Usefulness, Perceived Ease of Use, and Discomfort have the most significant influence on the consumers’ acceptance of cashless payment services with R-square of 71.4%.

This paper is devoted to the study of reproducing kernels on 2-inner product Hilbert spaces. We focus on a new structure to produce reproducing kernel Hilbert and Banach spaces. According to multi-variable computing, this structures can be useful in electrocardiographs, machine learning and economy

Environmental effects and climate change are lately representing an increasing strain of the coastal areas which topography strongly depends on these conditions. However, the processes by which weather and environmental phenomena influence the highly variable beach morphology are still unknown. A continuous monitoring of the beach environment is necessary to implement protection strategies. This paper presents the results of an innovative study performed on a coastal area using satellite remote sensing data with the aim of understanding how environmental phenomena affect beaches. Two-years of synthetic aperture radar (SAR) Sentinel-1 images are used over a test area in Noordwijk, the Netherlands. At the same time as the SAR acquisitions, information on tidal and weather conditions are collected and integrated from nearby meteorological stations. Dedicated codes are implemented in order to understand the relationship between the SAR amplitude and the considered phenomena: wind, precipitation, tidal conditions. Surface roughness is taken into account. The results indicate a strong correlation between the amplitude and the wind. No particular correlation or trend could be noticed in the relation with the precipitation. The analysis of the amplitude also shows a decreasing trend moving from the dry area of the beach towards the sea and the correlation coefficient between the amplitude and the tide level gets negative with the increase of the water content.

Adolescents most often experience mild acute COVID-19 but may still face fatigue and persistent symptoms such as post-COVID-19 condition (PCC) and post-infective fatigue syndrome (PIFS). We explored the fecal microbiota in a prospective controlled cohort of 136 non-hospitalized SARS-CoV-2-positive and 32 SARS-CoV-2-negative controls aged 12–25 years. With a targeted qPCR approach, the quantities of 100 fecal bacterial taxa were measured at baseline (early convalescent stage) and after six months. Results: Faecalibacterium prausnitzii M21.2 and Gemmiger formicilis (both p&lt;0.001) were enriched in the SARS-CoV-2-positive participants compared to controls at baseline. Lower baseline abundance of Faecalibacterium prausnitzii M21/2 (p=0.013) and higher abundance of Clostridium spiroforme (p=0.006), Sutterella wadsworthensis (p&lt;0.001) and Streptococcus thermophilus (p=0.039) were associated with six-month fatigue. Sutterella wadsworthensis and Streptococcus thermophilus enrichment was additionally associated with PCC in the SARS-CoV-2-positive group (p&lt;0.001 and 0.042 respectively). Conclusions: In mild SARS-CoV-2 infection in adolescents and young adults, beneficial Faecalibacterium prausnitzii M21/2 and Gemmiger formicilis were enriched compared to SARS-CoV-2 negative controls. Additionally, both known (Faecalibacterium prausnitzii, Streptococcus thermophilus) and new (Clostridium spiroforme, Sutterella wadsworthensis) bacteria were associated with persistent symptoms in the COVID-19 infected group, warranting further exploration of the role of these bacteria in COVID-19 disease and PCC pathophysiology.

On average, one in ten patients die because of a diagnostic error and medical errors are the third largest cause of death in the US. While LLMs have been proposed to help doctors with diagnoses, no research results have been published on comparing the diagnostic ability of many popular LLMs on an openly accessible real-patient cohort. In thus study, we compare LLMs from Google, OpenAI, Meta, Mistral, Cohere and Anthropic using our previously published evaluation methodology and explore improving their accuracy with RAG.

We successfully fabricated Ag@Cu2O core-shell decorated on reduced graphene oxide (rGO) nanocomposites (ACRN) by a simple and convenient in situ substitution method. The properties of these ACRN with heterostructure layers were characterized by scanning and transmission electron microscopies and absorption spectroscopy. We used p-nitrophenol (4-NP) as a probe molecule to determine the chemical catalytic activity of the ACRN. Upon introduction of rGO, a high electron transfer efficiency was achieved; thus, the catalytic activity was improved significantly. Therefore, the ACRN exhibited significantly improved catalytic activity for the reduction of 4-NP and showed the high application value in the removal of toxic and harmful substances from water. In addition, the fabricated ACRN was used for the reduction of organic dyes and explosive pollutants to generate nontoxic products. Furthermore, the high charge redistribution and transfer among Ag, Cu2O and rGO in the ACRN induced the high catalytic reduction of organic pollutants, indicating the excellent potential of these materials for applications in water pollution treatment.

Various 4-aminotetrahydropyridinylidene salts were treated with aldehydes in alkaline medium. Their conversion to 5-substituted -hydroxyketones in a one-step reaction succeeded only with an aliphatic aldehyde. Instead, aromatic aldehydes gave 5-substituted -aminoketones or a single -diketone. The new compounds were characterized by spectroscopic methods and a single crystal structure analysis. Some of them showed anticancer and antibacterial properties.

Excess hepatic lipid accumulation is the hallmark of non-alcoholic fatty liver disease (NAFLD), for which no medication is currently approved. However, Glucagon-Like Peptide-1 Receptor Ag-onists (GLP-1RAs), already approved for treating type 2 diabetes, have lately emerged as possible treatments. Herein we aimed to investigate how the GLP-1RA Exendin-4 (Ex-4) affects the mi-croRNA (miRNAs) expression profile using an in vitro model of steatosis. Total RNA, including miRNAs, was isolated from untreated, steatotic, and Ex-4-treated steatotic cells and used for probing a panel of 799 highly curated miRNAs using NanoString technology. Enrichment path-way analysis was used to find the signaling pathways and cellular functions associated with the differentially expressed miRNAs. Our data shows that Ex-4 reversed the expression of a set of miRNAs. Functional enrichment analysis highlighted many relevant signaling pathways and cellular functions enriched in the differentially expressed miRNAs, including hepatic fibrosis, in-sulin receptor, PPAR, Wnt/β-Catenin, VEGF, and mTOR receptor signaling pathways, fibrosis of the liver, cirrhosis of the liver, proliferation of hepatic stellate cells, diabetes mellitus, glucose metabolism disorder and proliferation of liver cells. Our findings suggest that miRNAs may play essential roles in the processes driving steatosis reduction in response to GLP-1R agonists, which warrants further functional investigations.

CD44 has been known as a marker of tumor initiating cells, and plays pro-tumorigenic functions in many cancers. The splicing variants play critical roles in malignant progression of cancers by promoting the stemness, cancer cell invasion or metastasis, and resistance to chemo- and radiotherapy. To understand each CD44 variant (CD44v) function is essential to know the property of cancers and establishment of the therapy. However, the function of the variant 4-encoded region has not to be elucidated. Therefore, specific monoclonal antibodies (mAbs) against the variant 4 are indispensable for basic research, tumor diagnosis, and therapy. In this study, we established anti-CD44 variant 4 (CD44v4) monoclonal antibodies (mAbs) by immunizing mice with a peptide containing the variant 4-encoded region. We next performed flow cytometry, western blotting, and immunohistochemistry to characterized them. One of the established clones (C₄₄Mab-108; IgG₁, kappa) reacted with CD44v3-10-overexpressed Chinese hamster ovary-K1 cells (CHO/CD44v3-10). The K_D of C₄₄Mab-108 for CHO/CD44 v3-10 was 3.4 × 10⁻⁷ M. In western blot analysis, C₄₄Mab-108 detected CD44v3-10 in the lysate of CHO/CD44v3-10 cells. Furthermore, C₄₄Mab-108 stained formalin-fixed paraffin-embedded oral squamous carcinoma tissues in immunohistochemistry. These results indicated that C₄₄Mab-108 is useful to detect CD44v4 in various applications.

Endoplasmic reticulum (ER) stress perturbs cell homeostasis and induces the unfolded protein response (UPR). In breast cancer, this process is activated by oestrogen deprivation and is associated with tamoxifen resistance. We present evidence that the transcription factor SOX2 and the long noncoding RNA SOX2 overlapping transcript (SOX2OT) are up-regulated in oestrogen receptor-positive (ER+) breast cancer and in response to oestrogen deprivation. We examined the effect of the UPR on SOX2 and SOX2OT expression, and the effect of SOX2OT on UPR pathways in breast cancer cell lines. The induction of the UPR by thapsigargin or glucose deprivation up-regulates SOX2OT expression. This up-regulation is also shown with the anti-oestrogen 4OH-tamoxifen and mTOR inhibitor everolimus in ER + breast cancer cells that are sensitive to oestrogen deprivation or everolimus treatment. SOX2OT overexpression decreased BiP and PERK expression. This effect of SOX2OT overexpression was confirmed on BiP and PERK pathway by q-PCR. Our results show that a long noncoding RNA regulates the UPR and evince a new function of SOX2OT as a participant of ER stress reprogramming of breast cancer cells.

The toxic effects of 4-octylphenol (4-OP) have been studied in species such as mouse and fish; however, the toxic effects of 4-OP in male specific niche cells has not been researched. In this study, we investigated the molecular mechanism of toxicity of 4-OP in mouse TM4 Sertoli cells. TM4 cells were treated with four concentrations (0, 10, 30, and 50 µM/mL) of 4-OP at time points 24, 48, and 72 h. Cell viability and apoptosis assay was conducted following exposure. 4-OP significantly decreased cell viability in a concentration- and time-dependent manner, and increased apoptosis. Quantitative PCR analysis showed that Bad, Bax, and Bak mRNA expression levels were higher in exposed cells than in the control, but Bcl-2 expression was decreased. Western blotting revealed that 4-OP induced activities of caspase-3 and phosphorylation of Bad in a concentration- and time-dependent manner. Additionally, cytochrome C protein did not colocalize with mitochondria marker dye by 24 h. Cytochrome c protein expression increased in a time-dependent manner with 50 µM/mL. These results suggest that 4-OP induces mitochondria-mediated apoptosis by regulation of Bcl-2 family proteins and caspase-3 activation in male Sertoli cells.

In this work, the solar light-induced redox photoactivity of the ZnO semiconductor material was used to prepare at room temperature CuxO-ZnO composite catalysts with a control of the chemical state of the copper oxide phase. The preparation of Cu2(I)O-ZnO and Cu(II)O-ZnO composite catalysts was achieved by using Cu(acac)2 in THF-water and Cu(NO3)2 in water as metallic precursor, respectively. Prior to the implementation of the photo-assisted synthesis method, the most efficient photoactive ZnO material was selected among different ZnO materials prepared by the low temperature polyol method and through the precipitation method with carbonates and carbamates as precipitation agent, by taking the photocatalytic degradation of the 4-chlorophenol compound in water under simulated solar light as model reaction. The ZnO support materials were characterized by XRD, BET, TGA, SEM and TEM, and the synthesis method was strongly influencing their photoactivity in terms of 4-chlorophenol degradation and of total organic carbon removal. The most photoactive ZnO material was prepared by precipitation with carbonates and calcined at 300°C, and was taking advantage of a high specific surface area and a small mean crystallite size for achieving a complete 4-chlorophenol mineralization within 70 min of reaction, with a minimum Zn2+ released to the solution due to surface photocorrosion. Beside thermal catalysis applications, this work opened a new route for the facile synthesis of Cu2O-ZnO heterojunction photocatalysts, that could take advantage under solar light of the heterojunction built between the p-type semi-conductor Cu2O with direct visible light band gap and the ZnO semiconductor phase.

Exposure to predator scent (PS) has been used as a model of stress associated with danger to life and body integrity. We tested the hypothesis that repeated PS exposure alters the excitability of serotonin (5-HT) neurons of the dorsal raphe nucleus. To study the mechanisms involved, we approached serum and adrenal corticosterone and aldosterone concentrations, as well as cortical brain-derived neurotrophic factor (BDNF) expression. Adult male Sprague-Dawley rats were exposed to PS for ten minutes daily for ten consecutive days. Two weeks after the last exposure, electrophysiological and biochemical assessments were performed. Measurements by in vivo electrophysiology showed increased spontaneous firing activity of 5-HT neurons in rats exposed to PS. PS exposure resulted in reduced serum corticosterone and aldosterone concentrations. Concentrations of both corticosteroids in the adrenal glands, as well as the relative weight of the adrenals, were unaffected. The gene expression of hippocampal BDNF of rats exposed to PS remained unaltered. In conclusion, repeated exposure of rats to PS leads to enhanced firing activity of 5-HT neurons accompanied by reduced serum, but not adrenal aldosterone and corticosterone concentrations. Reduced corticosteroid concentrations in the blood appear to be the result of increased metabolism and/or tissue uptake rather than altered steroidogenesis. The decrease in circulating corticosterone in rats experienced repeated PS may represent part of the mechanisms leading to increased excitability of 5-HT neurons. The increase in 5-HT neuronal firing activity might be an important compensatory mechanism designated to diminish the harmful effects of the repeated PS exposure on the brain.

Nonlinear catastrophes caused by geological fluids are a fundamental issue in rock mechanics and the geoengineering hazard field. For the consideration of hydrodynamic force on red-bed mudstone softening damage, X-ray visualization test on the fissure flow in mudstone block failure under hydrodynamic force was performed in this study based on block scale and the physical phenomena of fissure seepage and nonlinear diffusion were further explored. A new method for evaluating the hydro-damage degrees of rocks using an X-ray image analysis was proposed, and the quantitative relation of diffusion coefficients of hydro-damage and seepage was established. The research results revealed that the hydrodynamic force promoted the fluid-filled fissure behavior in mudstone specimen failure. Also, the seepage and diffusion phenomena of fluid in rocks during failures were indicated using X-ray imaging. A dual mechanical behavior was presented in the nonlinear seepage and abnormal diffusion of a red mudstone geological body under hydrodynamic conditions. The damaged degree of mudstone was aggravated by the effect of hydrodynamic force, and the initial seepage–diffusion coefficient with respect to lower hydro-damage was larger than the final seepage–diffusion coefficient with respect to higher hydro-damage of rocks with a decreasing nonlinear trend.

We extended our model of the S1 tubular segment to address the mechanisms by which SGLT1 interacts with lateral Na/K pumps and tight junctional complexes to generate isosmotic fluid reabsorption via tubular segment S3. The strategy applied allowed simulation of laboratory experiments. Reproducing known experimental results constrained the range of acceptable model outputs and contributed to minimizing the free parameter space. 1. In experimental conditions, published Na and K concentrations of proximal kidney cells were found to deviate substantially from their normal physiological levels. Analysis of the mechanisms involved suggested insufficient oxygen supply as the cause and indirectly, that a main function of the Na/H exchanger (NHE3) is to extrude protons stemming from mitochondrial energy metabolism. 2. The water path from the lumen to the peritubular space is through aquaporins on the cell membrane and claudin-2 at paracellular tight junctions, with a smaller additional contribution to water transport by the coupling of 1 glucose:2 Na:200 H2O in SGLT1. 3. A Na+-uptake component passed through paracellular junctions by solvent drag in Na- and water-permeable claudin-2, thus bypassing the Na/K-pump, in agreement with the findings of early studies. 4. Electrical cross talk between apical rheogenic SGLT1 and lateral rheogenic Na/K pumps results in tight coupling of luminal glucose uptake and transepithelial water flow. 5. Isosmotic transport is achieved by Na-mediated ion recirculation at the peritubular membrane.

Seed longevity is a crucial trait for the seed industry and genetic resource preservation. To develop excellent cultivars with extended seed lifespans, it is important to understand the mechanism of keeping seed germinability long-term and to find useful genetic resources as prospective breeding materials. This study was conducted to identify the best cultivars with a high and stable seed longevity trait in the germplasm of rice (Oryza sativa L.) and to analyse the correlation between seed longevity and embryonic RNA integrity. Seeds from 69 cultivars of the world rice core collection selected by the NIAS in Japan were harvested in different years and subjected to long-term storage or controlled deterioration treatment (CDT). The long-term storage (4 °C, RH under 35%, 10 years) was performed on seeds harvested in 2010 and 2013. The seeds harvested in 2016 and 2019 were used for CDT (36 °C, RH of 80%, 40 days). Seed longevity and embryonic RNA integrity were estimated by a decrease in germination rate and RNA integrity number (RIN) after long-term storage, or CDT. The RIN value was obtained by electrophoresis of total RNA extracted from seed embryos. Seeds of ‘Vandaran (Indica)’, ‘Tupa 729 (Japonica)’, and ‘Badari Dhan (Indica)’ consistently showed higher seed longevity and embryonic RNA integrity both under long-term storage and CDT conditions, regardless of the harvest year. A strong correlation (R2 = 0.93) was observed between germination rates and RIN values of the seeds after long-term storage or CDT among nine cultivars selected based on differences in their seed longevity. The study findings revealed the relationship between rice seed longevity and embryo RNA stability and suggested potential breeding materials, including both Japonica and Indica cultivars, for improving rice seed longevity.

Lipophilicity can be measured with different methods, such as Shake-Flask or liquid chromatography. HPLC presents the advantage of overcoming solubility issues and therefore extending the range of lipophilicity to high values. A specific HPLC method, called ELogD, had been developed 20 years ago on a C₁₆-amide stationary phase, enhancing hydrophobic and hydrogen bond interactions to mimic octanol-water partition. The emergence of novel stationary phases added to the need for a less complex mobile phase has led to the development of a new HPLC assay called alphaLogD, applicable to neutral and basic compounds at pH 7.4, that combines superficially porous particles, a high number of equilibriums between solutes and stationary phase, and results in a lower number of isocratic methods to determine the logk’_w at a higher throughput. Statistical studies have been run to successfully evaluate the alphaLogD method compared to the Shake-Flask method and to allow this lipophilicity measurement into the so-called Beyond-Rule-of-5-molecules space.

The ordered Ca3TaGa3Si2O14 and disordered La3Ga5SiO14 crystals of the lantangallium silicate family were grown by the Czochralski method. The independent coefficients of thermal expansion of crystals αc and αa were determined by X-ray powder diffraction based on the analysis of X-ray diffraction spectra measured in the temperature range of 25÷1000°C. It is shown that in the temperature range of 25÷800°C the thermal expansion coefficients are linear. At temperatures above 800°C there is a nonlinear character of the thermal expansion coefficients associated with a decrease in the Ga content in the crystal lattice of the lantangallium silicate family crystals.

Macromolecular crystallography at cryogenic temperatures has so far provided the majority of the experimental evidence that underpins the determination of the atomic structures of proteins and other biomolecular assemblies by means of single crystal X-ray diffraction experiments. One of the core limitations of the current methods is that crystal samples degrade as they are subject to X-rays, and two broad groups of effects are observed: global and specific damage. While the currently successful approach is to operate outside the range where global damage is observed, specific damage is not well understood and may lead to poor interpretation of the chemistry and biology of the system under study. In this work, we present a phenomenological model in which specific damage is understood as the result of a single process, the steady excitation of crystal electrons caused by X-ray absorption, which acts as a trigger for the bulk effects that manifest themselves in the form of global damage and obscure the interpretation of chemical information from XFEL and synchrotron structural research.

Herpesviruses produce a plethora of pleomorphic and heterogeneous particle populations. The composition and biological role of these is not understood. Detailed analysis has been challenging due to the lack of multidimensional identification and purification methodologies. Fluorescence-activated cell sorting (FACS), originally developed to sort objects with at least ten thousand-fold larger volumes, has recently been applied to cellular exosomes as well as viral particles and has been dubbed nanoscale flow cytometry or “flow virometry”. In comparison to other nanoparticles, herpesvirus concentrations can be measured with high precision using simple culturing methods. Here, we used this unique capability to evaluate a standard FACS sorter. We demonstrate that detection and separation capabilities were insufficient to distinguish infectious fluorescent viral populations from populations lacking fluorescence and infectivity. Moreover, fluorescent populations did not contain single virus particles but mostly aggregates. On top, analysis of viral samples by flow cytometry was confounded by swarm detection, as multiple objects are measured simultaneously and interpreted as a single object. Despite these technical difficulties, comparison of crude supernatant to gradient purified HCMV revealed that infectious virus is a minor proportion of the particles released from infected cells. Our data stress the need for a set of standardized controls and protocols when applying FACS to biological nanoparticles and highlights technical challenges that need to be solved before flow virometry can achieve its full potential.

Autoimmune polyglandular syndrome (APS) comprises a complex association of autoimmune pathological conditions. APS Type 1 originates from loss-of-function mutations in the autoimmune regulatory (AIRE) gene. APS2, APS3, and APS4 are linked to specific HLA alleles within the major histocompatibility complex, with single nucleotide polymorphisms (SNPs) in non-HLA genes also contributing to disease. In general, variability in the AIRE locus and the presence of heterozygous loss-of-function mutations can impact self-antigen presentation in the thymus. In this study, Whole Exome Sequencing (WES) was performed on a sixteen-year-old female APS3A/B patient to investigate the genetic basis of her complex phenotype. The analysis identified two variants (p.Arg111Trp and p.Thr101Ile) of the hepatitis A virus cell receptor 2 gene (HAVCR2) encoding for the TIM-3 (T cell immunoglobulin and mucin domain 3) protein. These variants were predicted, through in silico analysis, to impact protein structure and stability, potentially influencing the patient’s autoimmune phenotype. While Confocal Microscopy analysis revealed no alteration in TIM-3 distribution between PBMCs isolated from the patient and those of a healthy donor, RT-qPCR showed reduced TIM-3 expression in the patient’s cells. A screening conducted on a cohort of thirty APS patients indicated that the p.Thr101Ile and p.Arg111Trp mutations were unique for the proband. This study opens the pathway for the search of TIM-3 variants possibly linked to complex autoimmune phenotypes, highlighting the potential of novel variant discovery in contributing to APS classification and diagnosis.

Polypharmacy, the use of multiple medications, is a prevalent issue globally that contributes to increased healthcare costs and places additional burdens on patients' organs. This study aims to reduce the incidence of polypharmacy in the emergency department. We conducted a retrospective review of randomly selected medical records from the Internal Medicine Department of Taipei MacKay Emergency Department, spanning from August 1, 2023, to October 31, 2023. For cases identified as involving polypharmacy, pharmacists provided medication education using the TRM Polypharmacy Interview Guide, while social workers contacted patients via phone to recommend follow-up visits for deprescribing. Patients experiencing polypharmacy were significantly older than those on appropriate medication regimens (79.8 vs. 67.3 years, p=0.002). After deprescribing interventions, the average number of medications for polypharmacy patients was 5.9 higher than for those receiving appropriate prescriptions (9.2 vs. 3.3, p=0.001). The most common conditions associated with polypharmacy were diabetes mellitus, hypertension, and arrhythmia. Polypharmacy poses a significant medication management challenge, with affected patients taking an average of 6.9 more medications than those on appropriate treatment regimens. Our team’s resource management module successfully reduced the incidence of polypharmacy by 8.4% in the emergency department.

Let $\mathcal{N}$ be an arbitrary class of matroids, closed under isomorphism. For $k$ a positive integer, we say that $M \in \mathcal{N}$ is \emph{$k$-minor-irreducible} if $M$ has no minor $N \in \mathcal{N}$ such that $1\leq\left|E\left(M\right)\right|-\left|E\left(N\right)\right|\leq k $. Tutte's Wheels and Whirls Theorem establish that, up to isomorphism, there are only two families of 1-minor-irreducible matroids in the class of 3-connected matroids. More recently, Lemos classified the 3-minor-irreducibles with at least 14 elements in the class of triangle-free 3-connected matroids. Here we prove a local characterization for the 2-minor-irreducible matroids with at least 11 elements in the class of triangle-free 3-connected matroids. This local characterization is used to establish two new families of 2-minor-irreducible matroids in this class.

Image fusion is a useful tool for producing a high-resolution multispectral image to be used for land use and land cover mapping. In this study, we use nine pansharpening algorithms namely Color Normalized (CN), Gram-Schmidt (GS), Hyperspherical Color Space (HCS), High Pass Filter (HPF), Nearest-Neighbor Diffusion (NND), Principal Component Analysis (PCA), Resolution Merge (RM), Stationary Wavelet Transform (SWT), and Wavelet Resolution Merge (WRM) to fusion Worldview-3 multispectral Bands and panchromatic band. In spectral and spatial fidelity, several image quality metrics are used to evaluate the performance of pansharpening algorithms. The SWT and PCA algorithms showed better results compared to other pansharpening algorithms while GS and CN algorithms showed the worst results for the original image fusion. The effect of fusion on each band was separately investigated and according to the calculations, we found that the CoastalBlue band and the Blue band showed the best result and the NIR-1 band and NIR-2 band show the worst result for the original image fusion. In the end, we conclude that the choice of fusion method depends on the requirement of remote sensing application.

Lung nodule segmentation in CT images and its subsequent volume analysis can help determinethe malignancy status of a lung nodule. While several efficient segmentation schemes have beenproposed, only a few studies evaluated the segmentation’s performance for large nodules. In thisresearch, we contribute a semi-automatic system which is capable of performing robust 3-D segmen-tations on both small and large nodules with good accuracy. The target CT volume is de-noisedwith an anisotropic diffusion filter and a region of interest is selected around the target nodule ona reference slice. The proposed model performs nodule segmentation by incorporating a mean in-tensity based threshold in Geodesic Active Contour model in level sets. We also devise an adaptivetechnique using image intensity histogram to estimate the desired mean intensity of the nodule.The proposed system is validated on both lung nodules and phantoms collected from publicly avail-able diverse databases. Quantitative and visual comparative analysis of the proposed work withthe Chan-Vese algorithm and statistic active contour model of 3D Slicer platform is also presented.The resulting mean spatial overlap between segmented nodules and reference nodules is 0.855, themean volume bias is 0.10±0.2 ml and the algorithm repeatability is 0.060 ml. The achieved resultssuggest that the proposed method can be used for volume estimations of small as well as large-sizednodules.

Vilsmeier–Haack reaction of (E)-1-(1-(3,5-difluorophenyl)ethylidene)-2-phenylhydrazine (1) using dimethyl formamide in excess of phosphorous oxychloride by conventional method, resulted in the synthesis of title compound 3-(3,5-difluorophenyl)-1-phenyl-1H-pyrazole-4- carbaldehyde (2) in good yield and high purity. Structure characterization of the novel title compound was done by IR, ¹H NMR, ¹³C NMR and mass spectral analysis.

This paper presents a new optical, multi-functional, high-resolution 3-axis sensor which serves to navigate and can, for example, replace standard joysticks in medical devices such as electric wheelchairs, surgical robots or medical diagnosis devices. A light source, e.g. a laser diode is affixed to a movable axis and projects a random geometric shape on an image sensor (CMOS or CCD). The software in the downstream microcontroller identifies the geometric shape’s center, distortion and size, then calculates X, Y, and Z coordinates. These coordinates can then be processed in attached devices. The 3-axis sensor is characterized by its very high resolution, precise reproducibility and plausibility of the coordinates produced. In addition, optical processing of the signal provides a high level of safety against electromagnetic and radio frequency interference. The sensor presented here is adaptive and can be adjusted to fit a user’s range of motion (stroke and force). This recommendation aims to optimize sensor systems such as joysticks in medical devices in terms of safety, ease of use, and adaptability.

Since cART was introduced to treat AIDS, the mortality rate due to AIDS has markedly decreased and the convalescence of HIV-infected individuals has improved drastically. However, HIV-1 sexual transmission has made HIV become a global epidemic. Sacran is a megamolecular poly-saccharide extracted from cyanobacterium Aphanothece sacrum that exhibits numerous desirable characteristics for transdermic applications, such as safety as a biomaterial, a high moisture re-tention effect, the ability to form a film and hydrogel, and an anti-inflammatory effect. In this study, we evaluated the anti-HIV-1 effects of Sacran as a barrier to HIV transmission. Sacran inhibited HIV-1 infection and envelope-dependent cell-to-cell fusion. Moreover, we used a Transwell assay to confirm that sacran inhibited viral diffusion and captured viruses. The synergistic effects of sacran and other anti-HIV infection drugs were also evaluated.HIV-1 infections can be reduced through the synergistic effects of sacran and anti-HIV-1 drugs. Our study suggests the use of sacran gel to protect against HIV-1 transmission.

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs, n-3 PUFAs), including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA), are essential polyunsatu-rated fats primarily obtained from fatty fish and plant-based sources. Compelling evidence from preclinical and epidemiological studies consistently suggests beneficial effects of ω-3 PUFAs on bone health and healthy aging processes. However, clinical trials have yielded mixed results, with some failing to replicate these benefits seen in preclinical models. This contraindication is mainly due to challenges such as low bioavailability, potential adverse effects with higher doses, and susceptibility to oxidation of ω-3 fatty acids, hindering their clinical effectiveness. This review provides an in-depth analysis of recent findings, focusing on clinical perspectives and encom-passing all relevant published studies to date, including preclinical and epidemiological research, with an emphasis on the role of omega-3 fatty acids in promoting bone health and supporting healthy aging. Additionally, it explores strategies to improve ω-3 PUFA efficacy, including na-noparticle encapsulation and incorporation of specialized pro-resolving mediators (SPM) derived from DHA and EPA, to mitigate oxidation and enhance solubility, thereby improving therapeutic potential. By consolidating evidence from various studies, this review underscores current in-sights and future directions in leveraging ω-3 PUFAs for therapeutic applications.

Cocrystallizaiton could improve most physicochemical properties of specific active pharmaceutical ingredients, which has great potential in pharmaceutical development. In this study, the cocrystal of nitrofurantoin and 4-aminobenzoic acid was prepared with solid-state (solvent-free or green-chemistry) grinding approach, and the above cocrystal has been characterized by Raman and terahertz vibrational spectroscopic techniques. Spectral results show that the vibrational modes of the cocrystal within the whole spectral region are different from those of the corresponding parent materials. The dynamic process of such pharmaceutical cocrystal formation has also been monitored directly with Raman spectra. These results offer us unique means for characterizing the cocrystal conformation from molecule-level and also provide us rich information about the reaction dynamic of cocrystal formation within pharmaceutical fields.

Since December 2019, the COVID-19 virus has rapidly spread worldwide, prompting the World Health Organization (WHO) to declare it a pandemic and advocate for the widespread use of face masks to mitigate transmission. In this review, we delve into the potential impact of prolonged face mask use on temporomandibular joint (TMJ) health, an area that has garnered limited attention amidst COVID-19 research. Research has revealed that improper mask fit, and constant readjustment can lead to TMJ abnormalities. Similarly, there is a demonstrated correlation between continuous mask usage and increased incidence of headaches, temporomandibular pain, and diminished quality of life. Many studies have highlighted discomfort in the preauricular area, headaches, TMJ noises, headache, jaw pain, and muscle fatigue, as well as dermatological disorders that have been attributed to prolonged mask wear and its impact on TMJ. Our study catalyzes future research endeavors, urging a deeper exploration of the implications of long-term mask wear, not only in the context of the COVID-19 pandemic but also among occupational groups regularly exposed to extended mask use. By unraveling the complexities of TMJ health in the face of evolving preventive measures, we aim to enhance our understanding and safeguard the well-being of mask-wearers worldwide.

Glioblastomas (GBMs) are the most malignant and intractable of all cancers, with an unfavourable clinical prognosis for affected patients. The objective was analysis the sensitivity of GBM cells to the antimicrobial peptides (AMPs) cathelicidin (LL-37) and protegrin-1 (PG-1), both alone and in combination with chemotherapy, to predict overall survival (OS) in the patients. The study was conducted on 27 GBM patients treated in the neurosurgical departments of the Almazov Medical Research Centre (Saint-Petersburg, Russia) from 2021 to 2024. The cytotoxic effects of chemo-therapy, AMPs and their combinations on brain tumor cells were assessed by MTT assay using 50%-inhibitory concentration (IC50). In GBM cells from the patients, LL-37 and PG-1 exhibited strong anticancer effects, surpassing those of chemotherapy drugs. These LL-37 and PG-1 anti-cancer effects were associated with a statistically significant increase in life expectancy and OS in GBM patients. These findings were confirmed by the experiments on rats with C6 glioma, where intranasal administration of LL-37 (300 μM) and PG-1 (600 μM) increased the life expectancy of the animals to 69 and 55 days, respectively, compared to 24 days in the control group (HR=4.139, p=0.0005; HR=2.542, p=0.0759). Additionally, the combination of LL-37 and PG-1 with chemo-therapy drugs showed that a high IC50 of LL-37 with cisplatin (cutoff >800 μM) in GBM cells was associated with increased life expectancy (19 vs 5 months, HR=4.708, p=0.0101) and OS in GBM patients. These combinations could be used in future GBM treatments.

Wastewater genomic surveillance is an efficient and economic approach to track infectious diseases and can help detect unusual epidemiological events. The current study uses this approach for the first time in Morocco to monitor the epidemiology of SARS-CoV-2 and Influenza A, B and RSV virus infections during the third wave of COVID-19 caused by the Omicron variant. The virome was concentrated from wastewater collected from two sewer sheds of two cities, Agadir and Inezgane, using the PEG/NaCl method. The viral copy number was determined using qRT-PCR. All 26 samples in both cities were tested positive for SARS-CoV-2 at various viral loads. For Influenza A virus, two samples were tested positive in Inezgane. The estimated SARS-CoV-2 viral RNA copy numbers observed were then used to estimate the number of infected individuals using the SEIR model. The number of viral copies of SARS-CoV-2 for Agadir and Inezgane varied from 82932 ± 15479 to 507865 ± 58759 copies/L and 61244 ± 8552 to 497506 ± 18061 copies/L, respectively. The estimated number of cases correlates positively with the number of reported cases. Next Generation Sequencing showed that samples contain the following two variants: BA.1 and BA.2 that have been detected in clinical samples. This study demonstrates the effectiveness and feasibility of wastewater genomic surveillance in monitoring pathogens such as SARS-CoV-2 in Morocco.

(3+1)D quantum mechanics is a four-dimensional quantum formalism, which is developed neither in a Minkowski spacetime, nor in a purely Hilbert space and not its metric is Lorentzian. This quantum mechanics also yields the quantum Einstein field equation in (3+1)D quantum spacetime. Every observable (3+1)D quantum spacetime can be found to contain internally hidden opposite spin quantum state, that results Supersymmetry. Closed continuous mappings of this hidden quantum state immediately yield more extra hidden dimensions including string. This string is found to be fundamentally eleven-dimensional (rather than lower dimensional) by nature within this quantum spacetime, which is necessarily a natural phenomenon of (3+1)D Quantum Mechanics.

The recognition of (1→3)-β-D-glucans (BGs) by β-1,3-D-glucan recognition protein (BGRP) found in invertebrates plays a significant role in the activation of toll pathway and pro-phenol oxidase system in insect host defense against fungal invasion. To examine the structural diversity of BGs in BGRP interaction, the binding specificity of BGRPs cloned from four different insectswas characterized using ELISA. Recombinant BGRPs expressed as Fc-fusion proteins of human IgG1 bound to solid phase BGs. Because of the binding specificities, the BGRPs were categorized into two different ultrastructure- binding characters. The BGRPs from Silkworm and Indian meal moth bound to BGs containing triple-helical structure. Other BGRPs from red flour beetle and yellow mealworm beetle showed no binding to triple-helical BGs, but to alkaline-treated BGs, which have partially opened helical conformation. These evidences suggest that the innate immune system distinguishes different BG conformations and it is equipped for the diversity of BG structures.

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a specific subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1's mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was safe and well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is safe and well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest.

Actively combating post-harvest food spoilage and waste can dramatically increase the efficiency of food utilization worldwide. In climacteric fruits, chemical treatments such as 1-MCP are an effective way of reducing post-harvest spoilage and waste by inhibiting the fruit’s ability to perceive ethylene. 1-MCP treatment is increasingly being used to explore the complex nature of ripening physiology at a fundamental level, however, differences in application and quantitation methods create difficulties in comparing conclusions across studies. Here we report an effective and reproducible method for 1-MCP application and quantitation for small-medium sized research applications. By use of surrogate alkene standards 1-butene and cis-2-butene, the highly volatile and elusive 1-MCP molecule can be identified and quantified by gas chromatography and subsequent standard curves may be developed. It is hoped that the methodology outlined here can help standardize consistent 1-MCP application for post-harvest research without excessive investment in specialized equipment.

(1) Background: In this work, a series of benzimidazole derivatives containing colchicine-like and cathechol-like moieties with methyl group substitution in the benzimidazole ring were evaluated for their in vitro antiproliferative, pro-apoptotic and antioxidative activity against highly invasive breast cancer cell line MDA-MB-231 and related impairment of tubulin dynamics; (2) Methods: MTT assay was used to evaluate the antiproliferative activity. In vitro tubulin polymerization assay as well as docking analysis was applied to prove the alterations in tubulin polymerization. Immunofluorescent and DAPI staining reveal the pro-apoptotic potential of benzimidazole derivatives and the effect on tubulin’s dynamics in living cells. The antioxidant activity was evaluated by scavenging of H2O2 and hypochlorite ion and ortho-phenanthroline tests; (3) Results: The compounds containing colchicine-like moiety displayed significant growth inhibitory effect against cancer cell line as was highlighted the role of methyl functional group on the tubulin aggregation and blockage of mitosis. All compounds showed an ability to scavenge H2O2, while the compounds with cathecol-like moiety were more effective against hypochlorite ion and chelation of iron; (4) Conclusions: The benzimidazole derivative containing colchicine-like moiety and methyl group substitution in benzimidazole ring is a potential antiproliferative and microtubule destabilizing agent.

Bismuth sodium titanate thin films (BNT) were deposited on Pt/SiN substrates by Sol-Gel spin coating technique under O2 atmosphere. Microstructural, structural, and electrical properties of the obtained film were investigated. Scanning electron microscopy and atomic force microscopy micrographs were used to analyze the microstructure of the films. Furthermore, EDX analysis revealed a Na-deficient composition for the obtained film. X-ray diffraction and Raman spectroscopy allowed the identification of a pure perovskite BNT phase. Dielectric, ferroelectric, and leakage current measurements revealed good frequency stability of the dielectric constant and dielectric losses for BNT thin film. The results are discussed in terms of Na-deficiency effects on the defect structure of BNT. Further, the film showed attractive electrostatic energy storage properties with energy density that exceeds 1.04 J/cm3 under E = 630 kV/cm.

Label-free optical biosensors such as interferometers can provide comparable limit of detection to widely used enzyme-linked immunosorbent assays, while minimizing the number of steps and reducing false positives/ negatives. In 2020, authors reported a novel optofluidic Young interferometer (YI) that can provide real-time spatial information on refractive index changes occurring along the length of sensor and reference channels. Herein, we exploited these features of the YI to study interactions of biomolecules with recognition elements immobilized in selected regions of agarose gel in the sensor channel. We showed that the YI is well suited for biosensing of an exemplar biomolecule, streptavidin, in the absence and presence of bovine serum albumin interferent. Equally, we coupled the YI with electrokinetic transport to reduce the time for biosensing.

The detection, characterization, and monitoring of SARS-CoV-2 recombinant variants is a challenge to public health authorities worldwide. Recombinant variants, composed of two or more SARS-CoV-2 lineages, often have unknown impacts on transmission, immune escape, and virulence in the early stages of emergence. We examined 4,213 SARS-CoV-2 recombinant SARS-CoV-2 genomes collected between 2020 and 2022 from California to describe regional and statewide trends in prevalence. Many of these recombinant genomes, such as those belonging to the XZ lineage, or novel recombinant lineages, likely originated within the state of California. We discuss the challenges and limitations surrounding Pango lineage assignments, the use of publicly available sequence data, and adequate sample sizes for epidemiologic analyses. Although these challenges will continue as SARS-CoV-2 sequencing volumes decrease globally, this study enhances our understanding of SARS-CoV-2 recombinant genomes to date while providing a foundation for future insights into emerging recombinant lineages.

(1) Background: Among the chronic complications of type 2 diabetes mellitus, cancer became the leading cause of death in several countries. Our objective was the determination of whether prevalent type 2 diabetes mellitus is associated with a higher incidence of cancer. (2) Methods: This study is a nationwide analysis performed in Hungary. Study population was divided into a group with type 2 diabetes mellitus and into a non-diabetic group. The primary outcome was the risk related to overall cancer incidence. A key secondary outcome was the overall incidence of cancer in distinct study years. Further outcomes were the annual percent changes. (3) Results: The odds ratio related to the overall incidence of cancer was 2.50 (95% confidence interval: 2.46-2.55, P&lt;0.0001) in patients with diabetes as related to controls. The odds ratio was higher in males than in females. The highest risk was found in the 18-39-year-old subgroup. The annual cancer incidence rate declined in controls, but not in patients with diabetes. Several types of cancer showed a decreasing tendency in non-diabetic controls.; (4) Conclusions: type 2 diabetes is associated with a higher risk of cancer. High risk in young patients with type 2 diabetes suggests that these young individuals should be considered as a risk group.

Cardiotonic steroids (CTS) are a group of steroid compounds derived from certain plants and animals. CTS are selective inhibitors of Na,K-ATPase, so for a long time they were widely used for medical purposes to treat heart failure and some other diseases. However, over time, doctors gradually began to refuse this group of drugs due to their narrow therapeutic range and a number of serious side effects. However, in parallel with the rise and fall of interest in CTS as a drug, interest in them as a single class of high-affinity Na,K-ATPase inhibitors has only increased. Numerous data on the effect of CTS on signaling cascades and cell viability made impelling a search for a rationale for the existence of such a subtle biological regulator. A large number of studies devoted to the potential use of CTS in the treatment of neurodegenerative, oncological, immune and other diseases "revitalized" the already "written off" group of the drugs. If initially the role of exogenous (mainly plant origin) CTS was studied, then by the 90s of the XX century the study of the role of endogenous CTS and their regulatory effects became a popular trend in biology and physiology. The role of endogenous CTS was studied in details in the pathogenesis of cardiovascular diseases [1]. A large number of researchers have unanimously stated that endogenous CTS are very complex regulators of the development of pathological processes; however, the exact cause-and-effect relationship that would unambiguously explain the processes of synthesis, utilization, and the role of endogenous CTS has not yet been established. The effects of CTS in the frame of various regulatory schemes have been described, but the predominant number of studies was devoted to arterial hypertension, heart and renal failure, cancer [2–4], aging [5,6], and neuroinflammation. The effects of both endo- and exogenous CTS on blood cells and have been studied to a much lesser extent.

Piezoelectric c-axis oriented zinc oxide (ZnO) thin films, from 1.8 up to 6.6 µm thick, have been grown by radio frequency magnetron sputtering technique onto fused silica substrates. A delay line consisting in two interdigital transducers (IDTs) with wavelength λ = 80 µm was photolith-ographically implemented onto the surface of the ZnO layers. Due to the IDTs split finger con-figuration and metallization ratio (0.5), the propagation of both the fundamental, third and nineth harmonic Rayleigh waves is excited; also, three leaky surface acoustic waves (SAWs) were detected travelling at velocity close to that of the longitudinal bulk wave in SiO2. The acoustic waves propagation in ZnO/fused silica was simulated by using 2D finite-element method (FEM) tech-nique to identify the nature of the experimentally detected waves. It turned out that, in addition to the fundamental and harmonic Rayleigh waves, also high-frequency leaky surface waves are ex-cited by the harmonic wavelengths; such modes are identified as leaky-Sezawa (LS) waves under cut-off. The velocity of all the modes was found in good agreement with the theoretically calcu-lated values. The existence of a low-loss region for the Sezawa wave below the cut off was theo-retically predicted and experimentally assessed.