One of the influential factors in estimating the service life of reinforced concrete bridges (RCB) is determining the long-term seismic performance of these structures. Corrosion due to chloride ion diffusion leads to the destruction of critical members of the RCB during the useful life of the structure. So, the long-term seismic performance of the bridge deteriorates as a result. It is essential to study the effect of corrosion deterioration on the long-term seismic performance of bridges in the southern regions of Iran, near the coasts of the Persian Gulf and the Oman Sea, because of the seismicity of the region and high corrosion rate of reinforced concrete (RC) members is the result of environmental conditions. In order to investigate this issue, considering studies about environmental conditions of southern Iran, the onset time of corrosion in the columns, as seismic critical members of the bridge, was determined. Based on that, the corrosion's effect on characteristics of RC at specific time points during the bridge's useful life (0, 15, 30, 45, 60, 75 and 90 years) have been calculated. The effects of corrosion include deterioration of the core and cover concrete properties, steel bar and the connection between concrete and steel bar. In the next step, at each time point, according to the modified stress-strain relationships, the moment-curvature analysis of the bridge pier was done, and the properties of the plastic hinge were determined. Finally, based on the obtained data about plastic hinge characteristics at each time point, overload analysis of the bridge was performed in both longitudinal and transverse directions. Then the capacity curves of RCB were compared at the mentioned time-points. The results show that the capacity of the bridge deteriorates over time due to corrosion. Therefore, a proposal to increase the value of base shear design has been made to ensure the long-term seismic performance of RCB in corrosive environments.

Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus, is significantly underreported in Mongolia due to geographical remoteness, lack of early diagnostics, and poor clinical management. This study aimed to provide a more accurate estimate of CE in Mongolia by comparing data of surgical (reported) and diagnosed (unreported) cases, and assessing the challenges faced by rural doctors in disease management and surveillance. We collected data on surgical cases hospitalized between 2006-2016 and newly diagnosed CE cases in 2016 from eight provinces. Using a quasi-Poisson regression model of the collected data, we used extrapolation to estimate the number of diagnosed cases for the entire country. Additionally, fourty health professionals from all 21 provinces rated local clinical management for CE through a questionnaire. Results reveal that surgical cases (2.2 per year) represent only one-eighth of diagnosed cases (15.9 per year). The laboratory facilities, disease reporting, and cyst classification usage scored below 2. These results highlight the significant underreporting of CE in Mongolia and urges human and animal health experts, along with policymakers, to invest into combating CE, particularly in remote provincial areas. It also emphasizes the need for standard clinical management involving cyst classification according to WHO-IWGE, seamless integration of CE reporting and monitoring mechanisms, which can significantly contribute to the national and global burden estimation of CE.

Traditional photodynamic therapy (PDT), a clinical cancer therapeutic approach using light in killing cancer cells, is often limited by insufficient light penetration, inefficient photosensitizer energy transfer, and inadequate oxygen in hypoxic tumors. Employing X-ray to activate photosensitizer in PDT can potentially overcome these limitations. Here, we compared protocols to synthesize a novel nano-photosensitizer composed of a europium-doped yttrium oxide core with a silica shell (Y₂O₃:Eu@SiO₂) which can be utilized in such therapeutic method, i.e., X-ray activated PDT (XPDT). Transmission electron microscopy (TEM) and dihydroethidium (DHE) were utilized to evaluate the effects of various synthesis conditions on the characteristics of Y₂O₃:Eu@SiO₂ and their ability to generate reactive oxygen species (ROS). The in vivo tumor suppression effects of the Y₂O₃:Eu@SiO₂ were assessed by ¹⁸F-fluorothymidine position emission tomography (¹⁸F-FLT PET) in human ovarian cancer xenografts using radiation sensitive CAOV3 and radiation resistant SKOV3 cell lines. Our data revealed a positive correlation between nanoparticle condensation time and core size as well as a negative correlation between urea concentrations and core size. Addition of cetyltrimethylammonium bromide (CTAB) during core synthesis enhanced particle dispersion. Two silica coating conditions showed the greatest efficiency in the enhancement of ROS generation. Furthermore, our in vivo study revealed suppression of tumor growth by Y₂O₃:Eu@SiO₂ administration when compared to non-treated control. Silica shell provides flexibility to conjugate moieties that specifically target to cancers. This nano-photosensitizer demonstrates the significant promise for overcoming limitations of conventional PDT and combating various cancers in clinical applications.

In this research, a novel collector cetyl trimethyl ammonium chloride (CTAC) was used to separate hematite from quartz via reverse flotation for the first time. Micro-flotation tests showed that CTAC had a strong ability to selectively collect quartz and a separation of hematite from quartz could be accomplished with a concentration of 0.00263 mmol/L CTAC. Zeta-potential measurements indicated that the positive CTAC+ species could selectively increase the surface potential of quartz, but it had rather a weak effect on the hematite surface. X-ray photoelectron spectroscopy (XPS) detection indicated that CTAC had a stronger binding affinity to oxygen sites on the surface of quartz than that of hematite, resulting in a large amount of CTAC predominantly adsorbed on quartz rather than hematite.

We discuss the electrodeposition of two-dimensional (2D) Pt-nanostructures on HOPG achieved under constant applied potential versus a Pt counter electrode (Eappl = ca. - 2.2 V vs RHE). The deposition conditions are discussed in terms of the electrochemical behavior of the electrodeposition precursor (H2PtCl6). We performed cyclic voltammetry (CV) of the electrochemical Pt deposit on HOPG and on Pt substrates to study the relevant phenomena that affect the morphology of Pt deposition. Under conditions where the Pt deposition occurs and H2 evolution is occurring at the diffusion-limited rate (- 0.3 V vs RHE), Pt forms larger structures on the surface of HOPG, and the electrodeposition of Pt is not limited by diffusion. This indicates the need for large overpotentials to direct the 2D growth of Pt. Investigation of the possible effect of Cl- showed that Cl- deposits on the surface of Pt at low overpotentials, but strips from the surface at potentials more positive than the electrodeposition potential. The CV of Pt on HOPG is a strong function of the nature of the surface. We propose that during immersion of HOPG in the electrodeposition solution (3 mM H2PtCl6, 0.5 M NaCl, pH 2.3) Pt islands are formed spontaneously, and these islands drive the growth of the 2D nanostructures.

M184V is a single-base mutation in the YMDD domain of reverse transcriptase (RT). The M184V resistance-associated mutation is related to virological unresponsiveness to lamivudine (3TC) and emtricitabine (FTC) and induces high-level resistance to these two antiretroviral agents. M184V is rapidly selected in the setting of non-suppressive antiretroviral therapy (ART) and accumulates in the HIV reservoir. There were continuous efforts to evaluate the impact of M184V mutation on the treatment outcomes in people with HIV (PWH). Since lamivudine remains an extensively used part of recommended antiretroviral combinations, M184V is commonly detected in patients with virological failure. ART guidelines do not recommend the use of drugs impacted by resistance-associated mutations as they have been confirmed to comprise a risk factor for virological failure. However, previous authors suggest that 3TC/FTC can remain active even in the presence of M184V. Obtaining the viral resistance profile for each individual both treated or ART-naïve is a key challenge for lifelong treatment management.Given the potential benefits of lamivudine in the ART combinations, the investigation of M184V remains of high interest for clinicians and researchers. This is a review of literature for the challenges in treating both naïve and experienced individuals carrying the M184V resistance mutation, including virological failure, virological suppression, and resistance to ART.

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

Inflammation is an essential protective response against injury or infection. Physiological inflammation eliminates the pathogen, promotes tissue repair and healing. An exaggerated, out of control inflammation, however, can become pathological. Inflammation can generate secondary cell damage, inflame the vessels (endothelitis), activate coagulation processes. Among these pathogenetic factors (cell damage, inflammation, endothelitis, coagulopathies), self-amplification mechanisms can be created, spreading beyond the initial site, up to Multiple Organ Failure (MOF) and host death. If the inflammation does not resolve in a physiological way, the remodeling of the tissues can be maladaptive and lead to the onset of chronic inflammatory degenerative diseases. Diseases such as sepsis, burns, polytrauma, severe forms of influenza or COVID-19, are characterized by a condition of hyperinflammation, associated with a condition of immunosuppression. The initial events triggered by the pathogen (cell damage, interferon response in the case of viruses) ignite the inflammation by activating the inflammasome, the transcription factor NFkB, the release of pro-inflammatory eicosanoids (Prostaglandins, Leukotrienes, Thromboxanes) by neutrophils and macrophages. Hence, the cells of the innate immune system produce pro-inflammatory cytokines. Indeed, the ‘’eicosanoid storm’’ precedes the ‘’cytokine storm’’. Eicosanoids are a group of potent endogenous lipid mediators derived from omega-6 fatty acids Arachidonic Acid (AA). Eicosanoids include a group of molecules with pro-inflammatory (Prostaglandins, Leukotriens) and pro-coagulant (Thromboxanes) action. In addition, Arachidonic Acid (AA) is the source of Lipoxins (LXs). Lipoxins belong to a group of molecules collectively referred to as specialized pro-solving mediators (SPMs) which also include molecules derived from w-3 eicosapentaenoic acid (EPA): Resolvins (ReV-E sieres) and w-3 docohexanoic (DHA): Resolvins D-series (ReV D-series); Protectins (PTs); Maresins (MaRs). SPMs are important for the resolution phase of inflammation to take place properly. Their deficiency could be involved in both acute uncontrolled inflammation and chronic inflammation. The active regulation of the acute inflammatory process, integrating the precursors of Specialized Pro-resolving Mediators (SPMs), such as ⍵-6 and ⍵-3 in balanced ratio, or the SPMs themselves, could be a complementary therapeutic approach useful for taming the "storm of cytokines '' which characterizes exaggerated forms of inflammation. ⍵-3 and ⍵-6 are part of already widely used, readily available, inexpensive and safe supplements. Resolvins have already been included in clinical trials for various other inflammatory diseases (eye diseases, periodontal diseases).

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

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).

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

In this work, pure TiO₂ and binary nanocomposites of Fe₃O₄/TiO₂ and Ag/TiO₂ were synthesized in order to improve photocatalytic performance of these samples for degradation of 2, 4-dichlorophenol (2, 4-DCP) as an organic pollutant. A range of analytical techniques including XRD, DRS, SEM/EDX, and elemental mapping were employed to reveal the crystal structure, morphology and property of the nanocomposites. XRD data demonstrated that the prepared samples are purely in TiO₂ anatase phase and cubic spinel Fe₃O₄ exist in the synthesized nanocomposite. We calculated the TiO₂ crystal size from XRD patterns, in the range of 8.35-11.09 nm. The presence of Ag, Fe, O, and Ti atoms in the synthesized nanocomposites was confirmed by SEM/EDX. We obtained 30.43, 32.02 and 42.40 % degradation of 2, 4-DCP (100 ml 2, 4-DCP 40 ppm and 0.01 g catalyst) for pure TiO₂, Fe₃O₄/TiO₂ and Ag/TiO₂, respectively, after 180 min of irradiation under visible light. Similar conditions were employed for 2, 4-DCP degradation under UV irradiation, we obtained 53.05, 51.00 and 71.50 % degradation of 2, 4-DCP pure TiO₂, Fe₃O₄/TiO₂ and Ag/TiO₂, respectively. Thus, the synthesized binary nanocomposites exhibited higher photocatalytic activity compared to pure TiO₂ under visible light.

Thanks to the pioneering studies of Østerud and co-workers it is now increasingly understood that natural polyphenols present in marine oils play an essential role in protecting omega-3 lipids from oxidation and autooxidation ensuring that no proinflammatory products are formed after intake as it often happens with assumption of refined omega-3 concentrates. Strong antioxidants exerting multiple biological functions, olive biophenols are ideally suited to functionalize marine oils creating a synergy which has the potential to foster public health across the world. This study identifies suitable avenues to advance the sustainable production of health-beneficial formulations based on newly obtained natural marine oils and olive phenolic extracts. Important educational outcomes for bioeconomy educators conclude the study.

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

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

Development of new techniques of multimodal treatment, diagnostics of various neoplasms and improvement of these techniques can significantly increase the life expectancy of patients with carcinomas of the colon and abdominal cavity organs, since prevention of various side effects of radiation therapy is one of the main problems of oncological care. Electron irradiation is one of the most promising types of radiation therapy. There are no data on proliferation and apoptosis of the colon epithelium after irradiation with electrons, especially in different modes (single and summary). Aim of the study: Morphological evaluation of apoptosis and proliferation of colonic epithelium after local irradiation with electrons at doses 2 Gy and 25 Gy. Materials and methods. Colon fragments from sexually mature Wistar rats (n=50, body weight 200 ± 10 g) were divided into three groups: I - control (n = 10); II - experimental group (n = 20; local single electron irradiation at a dose of 2 Gy), III - experimental group (n=30), local fractional irradiation with electrons at a total dose of 25 Gy. They were studied by light microscopy using hematoxylin and eosin staining and immunohistochemical reactions with antibodies to Ki-67 and Cas3. Morphological disorders were accompanied by increased expression of pro-apoptotic molecules (caspase-3), and the period of regeneration by proliferative marker (Ki-67). Conclusions: Local fractional irradiation of the colon with electrons at a dose of 2 Gy and 25 Gy resulted in minor changes in the epithelium, a decrease in the number of goblet cells, but with preservation of regenerative potential, mild degenerative-dystrophic lesions. Intestinal crypts were damaged, leading to a decrease in Ki-67 and an increase in the number of caspase-3-positive epitheliocytes.

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

Bioactive glass (BG) represents a promising biomaterial for bone healing; here injectable BG pastes biological properties were improved by 25 wt% gelatin or chitosan, as well as mechanical resistance was enhanced by adding 10 or 20 wt% 3-Glycidyloxypropyl trimethoxysilane (GPTMS) cross-linker. Composites exhibited bioactivity as apatite formation was observed by SEM and XRD after 14 days immersion in SBF; moreover, polymers did not enhance degradability as weight loss was >10% after 30 days in physiological conditions. BG-gelatin-20 wt% GPTMS composites demonstrated the highest compressive strength (4.8±0.5 MPa) in comparison with 100% BG control (1.9±0.1 MPa). Cytocompatibility was demonstrated towards human mesenchymal stem cells (hMSC), osteoblasts progenitors and endothelial cells. The presence of 20 wt% GPTMS conferred antibacterial properties thus inhibiting the joint pathogens Staphylococcus aureus and Staphylococcus epidermidis infection. Finally, hMSC osteogenesis was successfully supported in a 3D model as demonstrated by alkaline phosphatase release and osteogenic genes expression.

The efficacy of chemotherapy depends on sensitivity and intrinsic or acquired drug resistance of cancer cells. The n-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs) are considered chemosensitizing agents and revertants of multidrug resistance by pleiotropic mechanisms. The specific mechanisms are not fully understood, but nowadays, it is widely accepted that there are a complex network of mechanisms, including alteration in gene expression, modulation of cellular proliferation and differentiation, induction of apoptosis, generation of reactive oxygen species and lipid peroxidation. A crucial mechanism in the control of cell drug uptake and efflux is related to n-3 LCPUFA influence on membrane lipid composition. The incorporation of docosahexaenoic acid in the lipid rafts produces significant changes in their physical-chemical properties affecting content and functions of transmembrane proteins, such as growth factors, receptors and ATP-binding cassette transporters. Of note, n-3 LCPUFAs often impact on the lipid compositions more in chemoresistant cells than in chemosensitive cells, suggesting their adjuvant role in cancer treatment.

There is an urgent need to better understand the mechanisms involved in scar formation in brain. It is well known that astrocytes are critically engaged in this process. Here we analyze in-cipient scar formation one week after a discrete ischemic insult to the cerebral cortex. We show that the infarct border zone is characterized by pronounced changes in the organization and subcellular localization of the major astrocytic protein AQP4. Specifically there is a loss of AQP4 from astrocytic endfoot membranes that anchor astrocytes to pericapillary basal laminae and a disassembly of the supramolecular AQP4 complexes that normally abound in these membranes. This disassembly may be mechanistically coupled to a downregulation of the newly discovered AQP4 isoform AQP4ex. AQP4 has adhesive properties and is assumed to facilitate astrocyte mo-bility by permitting rapid volume changes at the leading edges of migrating astrocytes. Thus, the present findings provide new insight in the molecular basis of incipient scar formation.

In cold-climate regions, road salt is used as a de-icer for winter road maintenance. The applied road salt melts ice and snow on roads, being washed off through storm sewer systems into nearby urban streams, harming the freshwater ecosystem. Addressing the gap in the knowledge regarding the use of deep learning approaches for urban stream water quality forecasting, the present work discusses our implementation of a “Graph Neural Network” - “Sample and Aggregate” (GNN-SAGE) model for forecasting chloride concentrations in the Credit River in Ontario, Canada. The proposed GNN-SAGE is compared to other models, including a Deep Neural Network based transformer (DNN-Transformer) and a benchmarking persistence model for 6 hours forecasting horizon. Ac-cording to the results, the GNN-SAGE model surpasses other models in providing accurate predic-tions of chloride concentrations within the assessed prediction window. Also, a SHAP analysis provides insight into the variables that influence the model’s forecasting, showing the impact of the spatiotemporal neighbouring data from the network and the seasonality variables on the model’s result. The GNN-SAGE model shows potential for use in real-time forecasting of water quality in urban streams, aiding in the development of regulatory policies to protect the vulnerable freshwater ecosystems in urban areas.

Deep eutectic solvents (DESs) have emerged as novel alternatives to common solvents and VOCs. Their employment as electrolytes in battery has been an area of intense research. In this context, understanding changes in physicochemical properties of DESs in the presence of Li salts becomes of utmost importance. Solvatochromic probes have potential to gauze such changes. It is reported herein that one such uv-vis molecular absorbance probe, Reichardt’s betaine dye 33, effectively manifests changes taking place in a DES Glyceline, composed of H-bond accepting salt choline chloride and H-bond donor glycerol in 1 : 2 molar ratio, as salt LiCl is added. Lowest energy intramolecular charge-transfer absorbance band of this dye exhibits 17 nm hypsochromic shift as up to 3.0 molal LiCl is added to Glyceline. The estimated ETN parameter shows linear increase with LiCl mole fraction. Spectroscopic responses of betaine dye 33, N,N-diethyl-4-nitroaniline and 4-nitroaniline are used to assess empirical Kamlet-Taft parameters of dipolarity/polarizability (π*), H-bond donating acidity (α) and H-bond accepting basicity (β) as a function of LiCl concentration in Glyceline. LiCl addition to Glyceline results in increase in α and no change in π*and β. It is proposed that added lithium interacts with oxygen of the –OH functionalities on the glycerol rendering the solvent with increased H-bond donating acidity. It is observed that pyrene, a popular fluorescence probe of solvent polarity, does respond to the addition of LiCl to Glyceline, however, the change in pyrene response starts to become noticeable only at higher LiCl concentration (mLiCl ≥ 1.5 m). Reichardt’s betaine dye is found to be highly sensitive and versatile in gauzing physicochemical properties of DESs in the presence of LiCl.

Background. Traumatic brain injury (TBI) is the main cause of disabilities over the industrialized countries. Cognitive decline appears in the chronic phase of the pathology consecutively to cellular and molecular processes. Here we described the use of KCC2, a neuronal-specific potassium-chloride transporters as potent biomarker to predict cognitive dysfunctions after TBI. Methods. Using neuronal and total exosomes collection from blood serum in control and TBI subjects we were able to anticipate the decline of cognitive performance. Results. After TBI, we observed a significative and persistant loss of KCC2 expression in the blood exosomes that is correlated to changes in network activity and cellular processes such as secondary neurogenesis. Also we correlated this KCC2 loss in expression to the appearance of the cognitive decline observed in mice and more particularly we correlate the KCC2 loss of expression to the appearance of the depressive-like behavior. Conclusion. According to our protocol, we were able to confirm our previous findings in agreement with the potential therapeutic effect of bumetanide in the prevention of the post traumatic depression after TBI, by restoring the KCC2 expression thus preventing the massive neuronal death of interneurons and the secondary neurogenesis effect observed in such model.

In this study, the effect of extraction conditions on the total phenolic content of clove buds was investigated. Clove buds were extracted using a deep eutectic solvents like mixtures choline chloride: lactic acid in the 1:2 molar ratio. Additionally, the HPLC-DAD method was used to determine the main components of the clove extracts, including eugenol, eugenol acetate, and β-caryophyllene. The conditions used in the extraction with choline chloride: lactic acid (molar ratio 1:2) included extraction temperature (t = 40 – 80°C), water addition (5.6 – 40%), and extraction time (30 – 90 min). Determination of the phenolic compounds was done by the Folin-Ciocalteu method. The optimum operating conditions for the total phenolic content were identified at 77°C, 30 min, and a water addition of 40%. Based on the results, the highest amount of eugenol (307.26 ± 8,44 mg/g dry raw material) was determined in clove extracts which were extracted under condition of 60°C, 22.8%, and 30 min.

The interfacial polymerization (IP) of piperazine (PIP) and trimesoyl chloride (TMC) has been extensively utilized to synthesize nanofiltration (NF) membranes. However, it is still a huge challenge to monitor the IP reaction, because of the fast reaction rate and the formed ultra-thin film. Herein, two effective strategies were applied to reduce the IP reaction rate: (1) the introduction of hydrophilic interlayers between the porous substrate and the formed polyamide layer, and (2) the addition of macromolecular additives in the aqueous solution of PIP. As a result, in situ Fourier transform infrared (FT-IR) spectroscopy was firstly used to monitor the IP reaction of PIP/TMC with hydrophilic interlayers or macromolecular additives in the aqueous solution of PIP. Moreover, the formed polyamide layer growth on the substrate was studied in a real-time manner. The in situ FTIR experimental results confirmed that the IP reaction rates were effectively suppressed and that the formed polyamide thickness was reduced from 138 ± 24 nm to 46 ± 2 nm according to TEM observation. Furthermore, an optimized NF membrane with excellent performance was consequently obtained, which included boosted water permeation of about 141–238 (L/m²·h·MPa) and superior salt rejection of Na₂SO₄ > 98.4%.

The seeds of red clover are heteromorphic and two color morphs can be visually recognized, light purple and yellow, resulting from heterozygosity and recessive homozygosity at two loci. Here, we report the responses of seed imbibition, seed germination, and early seedling growth of the two morphs to distilled water, sodium chloride, and complete nutrient solution. The sensitivity of red clover seeds to treatments increased with the stage of development in what seems to be a cumulative process. No differences were found in seed imbibition between morphs or between treatments. In seedling growth, on the contrary, treatments were always effective, but differences between morphs were only observed in seeds that were treated with nutrient solution, whereas in the intermediate stage of seed germination, the effects by treatments were observed together with the appearance of differences between morphs in distilled water and in the treatment by sodium chloride solution. Simultaneously, the superior performance of the yellow morph that was found in germination, which appears to be a trait stable across cultivars of red clover seeds, turned into a superior performance of the light purple morph in seedling growth.

Preeclampsia (PE) is a common pregnancy complication. It is associated with high maternal morbidity and mortality rates and intrauterine foetal growth restriction. This condition is characterised by high blood pressure and urinary protein levels. Apelin and galectin-3 (Gal- 3) are peptides involved in the regulation of body fluid homeostasis, inflammation and cardiovascular functions. This study aimed to determine the correlations amongst serum apelin and Gal-3 levels and insulin resistance (IR) in women with PE. Sixty patients with PE and 30 healthy controls participated in this study. The PE group had significantly lower apelin levels (p < 0.01) and higher Gal-3 levels (p < 0.05) than the control group. The PE group had higher serum glucose levels and β-cell functions than the control group. Moreover, patients with PE exhibited dyslipidaemia. Correlation analysis indicated that apelin and Gal-3 levels were not significantly correlated. Moreover, no correlation existed between the apelin levels and any measured parameters of the PE group. In conclusion, the elevations in serum Gal-3 levels with increments in IR-related parameters and lipid profiles reflect the possible contribution of Gal-3 to the harmful effects of IR and dyslipidemia levels on women with PE.

Anti-interferon (IFN)-γ autoantibodies are linked to varicella-zoster virus (VZV) infection. Given the elevated risks of herpes zoster (HZ) in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKi), we aimed to examine the relationship between anti-IFN-γ autoantibodies with HZ development in JAKi-treated patients. In twenty-four RA patients with new-onset HZ and forty-two without HZ, serum titers of anti-IFN-γ autoantibodies, plasma levels of IFN-γ, monocyte chemoattractant protein-1 (MCP-1), and IFN-γ inducible protein-10 (IP-10) were measured by ELISA. Significantly lower MCP-1 levels were observed in patients with HZ compared to those without (median, 98.21pg/ml, interquartile range (IQR) 77.63-150.30pg/ml versus 142.3pg/ml, IQR 106.7-175.6pg/ml, p&lt;0.05). There was no significant difference in anti-IFN-γ titers, IFN-γ levels, or IP-10 levels between patients with and without HZ. Three of 24 patients with HZ had severe HZ with multi-dermatomal involvement. Anti-IFN-γ titers were significantly higher in patients with severe HZ than in those with non-severe HZ (median 24.8ng/ml, IQR 21.0-38.2ng/ml versus 10.5ng/ml, IQR 9.9-15.0ng/ml, p&lt;0.005). In conclusion, patients with HZ had significantly lower MCP-1 levels than those without HZ, and patients with severe HZ had significantly higher titers of anti-IFN-γ than those with non-severe HZ. Given small sample size, our results need further validation in future studies.

The paper proposes a universal algorithm for parallelizing calculations that arise when using highly-optimized minimization functions available in many computing packages. The main idea of the proposed algorithm is based on the fact that although the “inner workings” of the minimization function used may not be known to the user, it inevitably uses in its work auxiliary functions that implement the calculation of the minimized functional and its gradient, which are usually implemented by the user, which means that in most cases they can be parallelized relatively easily. The paper discusses in detail both the parallelization algorithm and its software implementation using MPI parallel programming technology. Examples of the software implementation of the proposed algorithm are demonstrated using the Python programming language, but can be easily rewritten using the C/C++/Fortran programming languages.

We demonstrate, for the first time, a highly sensitive detection of 4-methylimidazole (4-MeI), a carcinogenic material, by applying an electric field enhancement technique using a terahertz (THz) metamaterial at the THz region. The THz metamaterials were fabricated with a metal array using an electric-field-coupled inductor-capacitor (ELC) resonator structure, and FDTD simulation showed good agreement with experimental results. We measured the THz spectra of the metamaterials to detect 4-MeI concentrations of 0, 1, 2, 5, 10, 15, and 20 mg/L. The resonance frequency of the metamaterial was shifted by approximately 8 GHz and transmittance at the resonance frequency increased to 2 x 10-3 as the concentration was increased, up to 20 mg/L. Our study provides new insight into application of metamaterials to detect carcinogen using a THz technique.

Cutaneous leishmaniasis (CL) is a neglected tropical disease, which causes severe skin lesions. Due to the lack of effective vaccines, and toxicity or reduced effectiveness of available drugs in addition to complex and prolonged treatments, there is an urgent need to develop alternatives for the treatment for CL with different mechanisms of action. In our effort to search for new promising hits against Leishmania parasites we prepared 18 acyl hydrazone derivatives of thiochroman-4-ones. Compounds were evaluated for their in vitro antileishmanial activity against the intracellular amastigote form of Leishmania panamensis and cytotoxic activity against human monocytes (U-937 ATCC CRL-1593.2). Our results show that derivatization of the thiochroman-4-ones with acyl hydrazones significantly enhances the antileishmanial activity. Among the compounds tested semicarbazone and thiosemicarbazone derivatives of thioflavanone 19 and 20 displayed the highest antileishmanial activities, with EC₅₀ values of 5.4 and 5.1 µM and low cytotoxicities (100.2 and 50.1 µM respectively), resulting in higher indexes of selectivity (IS).

Premature ovarian insufficiency (POI) is a highly prevalent disorder, characterized by the development of menopause before age of 40. Most cases are idiopathic; however, in some women the cause of this condition (e.g. anticancer treatment, genetic disorders, and enzymatic defects) may be identified. Although hormone replacement therapy, the principal therapeutic approach for POI, helps to alleviate the related symptoms, this does not effectively solve the issue of fertility. Assisted reproductive techniques also lack efficacy in these women. Thus, the effective approach to manage the patients with POI is highly warranted. Several mechanisms, associated with POI, have been identified, including lack of FSH receptor functioning, alterations in the apoptosis control, mutations in Sal-like 4 genes, thymulin or basonuclin-1 deficiency etc. The above-mentioned may be good targets for gene therapy in order to correct defects, leading to POI. The goal of this review is to summarize the current experience on the POI studies, that employed gene therapy, and to discuss the possible future directions in this field.

A shrimp oil rich in omega-3 lipids and carotenoids is obtained in remarkably high 5 wt% yield extending to pink shrimp processing waste (head and carapace) the circular economy approach to extract fish oil from fish processing by-products using d-limonene. Biobased limonene, a powerful antimicrobial and antioxidant agent, is an excellent solvent for both lipids and astaxanthin-based carotenoids preventing oxidative degradation during the extraction cycle including solvent and oil separation at 85°C. A new low cost route is established to extract valued marine oil from biowaste annually made available in over 2.2 million tonnes.

Cytokines secreted by individual immune cells regulate tissue regeneration and allow communication between various cell types. Cytokines bind to cognate receptors and trigger the healing process. Determining the orchestration of cytokine interactions with their receptors on their cellular targets is essential to fully understand the process of inflammation and tissue regeneration. To this end, we have investigated the interactions of Interleukin-4 cytokine (IL-4)/Interleukin-4 cytokine receptor (IL-4R) and Interleukin-10 cytokine (IL-10)/Interleukin-10 cytokine receptor (IL-10R) using in situ Proximity Ligation Assays in a regenerative model of skin, muscle and lung tissues in the mini-pig. The pattern of protein-protein interactions was distinct for the two cytokines. IL-4 bound predominantly to receptors on macrophages and endothelial cells around the blood vessels while the target cells of IL-10 were mainly receptors on muscle cells. Our results show that in situ studies of cytokine-receptor interactions can provide unravel the fine details of the mechanism of action of cytokines.

Bacterial infections are world-wide problem and resistant bacteria is increasing globally that lead to treatments failure. Thus, it is important to find new techniques that are effective for the treatment antibiotic-resistant microorganisms. Green medicine used for the medication of different bacterial infection. Therefore , the study aimed to evaluate the immunomodulatory activity of essential fatty acid semi carbazide (EFASC) compounds extracted from flaxseed to eradicate resistance pathogens . Crud extracts of Linum usitatissimum was extracted by hexane for extraction of EFASC. The results of LD₅₀ appear that a live suspension of E.coli was 0.49×10⁷ ,while HK E.coli was 10⁸ , 125 mg /ml were the optimum dose in stimulate immune response of EFASC which gave maximum dose of total WBC , Neutrophil and Monocyte count. The immunomodulatory activity appear that E.coli + EFASC released moderate levels of IL-4 . HK E.coli release higher IL-4 lead to increase the hypersensitivity and hyper responses of immune system. HK + EFASC immunogen revealed moderate increased in IL-12 mean level 0.99 pg /ml, HK bacteria recorded 1.49 pg/ml, while the mean of EFASC revealed no significant different compare with control. An effective protection was observed in immunized groups with HK E.coli and EFASC challenged with 100 of LD50 of a live E.coli.

It was the aim of this study to compare the ratio of salbutamol and its major metabolite salbutamol-4’-O-sulfate as well as the quantity excreted renally after oral and inhalative administration. Additionally, the excretion pattern after application of racemic salbutamol opposed to the pure enantiomer levosalbutamol was evaluated. For quantitation of the sulfonated metabolite of salbutamol, reference material was synthesized and characterized by NMR and HRMS. Urine samples were analyzed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Salbutamol is mainly metabolized by sulfotransferase 1A3 (SULT1A3), which is most abundantly found in the jejunum. A high first pass effect occurs upon oral administration, which leads to a higher amount of salbutamol-4’-O-sulfate in urine compared to unchanged salbutamol excreted within the first hour post administration. Thus, when administered orally, the proportion of metabolite to total salbutamol was higher than for inhalative administration in the early urinary excretion. Levosalbutamol is the favored enantiomer of SULT1A3 and therefore metabolized at a higher rate whereas racemic salbutamol shows a reduced proportion between metabolite and parent compound. The amount of sulfoconjugate was found higher than that of the parent compound for all urine samples except for those excreted in the first hour after inhalative administration.

Background: Cell-free plasma DNA (cfDNA) is composed of circulating extracellular DNA originating from apoptosis or cell necrosis. It is generally present in healthy individuals, but its levels increase in different clinical conditions, such as kidney disease, sepsis, myocardial infarction, trauma and cancer. Caspase-3 plays a central role in apoptosis, a mechanism of programmed cell death involved in the pathogenesis of chronic kidney disease (CKD). Methods: We compared cfDNA and caspase-3 levels in 25 CKD patients and in 10 healthy subjects, evaluating the modification of their concentrations according to CKD stage. We also analyzed the correlation between cfDNA and caspase-3 levels in CKD patients and the correlation between cfDNA and caspase-3 levels and creatinine and urea. Results: CfDNA and caspase-3 levels were higher in CKD patients compared to healthy subjects, in particular in patients with advanced renal disease. A positive correlation between cfDNA and caspase-3 levels and between cfDNA and caspase-3 and creatinine and urea was also observed. Conclusion: Patients with chronic kidney disease present higher levels of cfDNA and caspase-3 levels compared with healthy subjects. The worsening of renal damage and the increase in uremic toxin concentration are associated to higher levels of cfDNA and caspase-3 levels, thus reflecting a central role of apoptosis in the pathogenesis of CKD.

A novel effective vibrational mode was discovered in the conventional transducer with an array of orthogonal (square) regular piezoelectric rods in 1-3 piezocomposite, containing the damping backing and front matching layers. The operational resonance in the structure was determined as the Surface Acoustic Wave (SAW) on the backing boundary excited by the adjacent piezo-rods, with its frequency typically near 3 times lower the fundamental half-lambda conventional piezocomposite resonance. Pulse-echo sensitivity and transmitting sound-pressure-level (SPL) in air showed that the signal strength is roughly comparable to the industrial similar air transducers at the frequency range 100…700 kHz, where at these frequencies the lateral and longitudinal piezoelement dimensions in the conventional transducer design are typically close to each other causing interference with unwanted coupling modes. As was determined theoretically and proved in experiments, the backing SAW resonance effect in the transducer performance is inherent just to the regular periodic 1-3 piezocomposite structure, and does occur neither with randomly located/oriented piezo-rods, nor in the homogeneous piezo-plate at least with the same lateral cross-section as the connected to it backing. The purpose of the article is to investigate a newly discovered operational vibrational mode of a SAW type in 1-3 regular piezocomposite, other than piezoelectric resonance. The investigated phenomena can improve the transceiver sensitivity, bandwidth, providing lower drive voltage, and smaller and lighter weight ultrasonic transducers. Based on the piezocomposites with thickness’ 1…1.5 mm (rod resonance near 2…3 MHz), pillar width 0.2…0.8 mm, kerf width 0.1…0.4 mm, the transceivers with an operating frequency from 140 kHz to 650 kHz were designed and fabricated with a conventional backing of a mixture of high-density tungsten powder and epoxy, and a matching layer of a mixture of low-density glass bubbles and epoxy. Experimental evaluation of their acoustical performance showed expected characteristics suitable for practical applications.

Immune checkpoint blockade (ICB)-based therapy is revolutionizing cancer treatment by fostering successful immune surveillance and effector cell responses against various types of cancers. However, patients with HER2+ cancers are yet to benefit from this therapeutic strategy. Precisely, several questions regarding the right combination of drugs, drug modality, and effective dose recommendations pertaining to the use of ICB-based therapy for HER2+ patients remain unanswered. In this study, we use a mathematical modeling-based approach to quantify the growth inhibition of HER2+ breast cancer (BC) cell colonies (ZR75) when treated with anti-HER2; trastuzumab (TZ) and anti-PD-1/PD-L1 (BMS-202) agents. Our data show that a combination therapy of TZ and BMS-202 can significantly reduce the viability of ZR75 cells and trigger several morphological changes. The combination decreased the cell’s invasiveness along with altering several key pathways, such as Akt/mTor and ErbB2 compared to monotherapy. In addition, BMS-202 causes dose-dependent growth inhibition of HER2+ BC cell colonies alone, while this effect is significantly improved when used in combination with TZ. Based on the in-vitro monoculture experiments conducted, we argue that BMS-202 can cause tumor growth suppression not only by mediating immune response but also by interfering with the growth signaling pathways of HER2+ BC. Nevertheless, further studies are imperative to substantiate this argument and to uncover the potential crosstalk between PD-1/PD-L1 inhibitors and HER2 growth signaling pathways in breast cancer.

MicroRNAs (miRNAs) play important roles in the control of HIV-1 infection. Here, we performed RNAseq profilings of miRNAs and mRNAs expressed in CD4+ T-lymphocytes upon HIV-1 infection. Our results reveal significant alterations of miRNAs and mRNAs expression profiles in infected relative to uninfected cells. One of the miRNAs markedly downregulated in infected cells is miRNA-26a. Among the putative targets of miRNA-26a are CD59 receptor transcripts, which are significantly upregulated in infected CD4+ T-cells. Addition of miRNA-26a mimics to CD4+ T-cells reduces CD59 at both mRNA and surface protein levels, validating CD59 as a miRNA-26a target. Consistent with the reported inhibitory role of CD59 in complement-mediated lysis (CML), knocking-out CD59 in CD4+ T-cells renders both HIV-1 infected cells and progeny virions more prone to antibody-dependent CML (ADCML). Addition of miRNA-26a mimics to infected cells leads to enhanced sensitivity of progeny virions to ADCML, a condition linked to a reduction of CD59 packaging into released virions. Lastly, HIV-1-mediated downregulation of miRNA-26a expression is shown to be dependent on integrated HIV-1 expression but does not involve viral accessory proteins. Overall, these results highlight a novel mechanism by which HIV-1 limits ADCML by upregulating CD59 expression via miRNA-26a downmodulation.

Consumption is thus fundamentally related to sustainably because every decision pertaining to what to buy, what quantity the buy, how many to consume, or how to dispose of things has a direct influence on the natural world and the generations to come, and the overall impact of every single the customer's purchase is disastrous. A framework-based systematic literature review (SLR) was conducted to better comprehend the body of research on digital innovation and sustainability driving consumer behavior. This was done in order to acquire a deeper understanding of the studies that have already been done in this area. to provide (i) a comprehensive review of the current research landscape and (ii) a rich roadmap for future research. This study evaluated the literature especially in terms of theory, context, traits, and methodology. A total of 107 research articles published between 2013 and 2022 were found using scientific methods in the Scopus database. The findings showed that most research appears to have employed qualitative methodologies and was grounded in the setting of China and Italy. This review could help scholars better grasp the relationship between digital innovation and sustainability, opening the door for additional study and advancement in the field. Additionally, by extending the literature study and emphasizing the elements that can improve digital innovation and sustainability, practitioners will be given a better overall understanding of how to approach the problem.

SMARCA4-deficient non-small cell lung cancer (NSCLC) is a more recently recognized subset of NSCLC. We describe the 18F-fluorodeoxyglucose (FDG) PET/CT findings in a rare case of SMARCA4-deficient NSCLC and response to therapy. A 45-year-old male patient with a history of heavy smoking (10 years) underwent an 18F-fluorodeoxyglucose (FDG) PET/CT dynamic (chest) + static (whole-body) scan for diagnosis and pre-treatment staging. 18F-FDG PET/CT showed an FDG-avid mass in the upper lobe of the left lung (SUVmax of 22.4) and FDG-avid lymph nodes (LN) in the left pulmonary hilar region (SUVmax of 5.7). In addition, there are multiple metastases throughout the body, including distant LNs, adrenal glands, bone, and brain. Pathological findings confirmed SMARCA-4 deficient NSCLC. After 4 cycles of chemotherapy and immune checkpoint inhibitors（ICI）, the patient underwent again an 18F-FDG PET/CT scan (including dynamic scan) for efficacy evaluation. We report cases that deepen the understanding of the 18F-FDG PET/CT presentation of SMARCA4-deficient NSCLC as well as dynamic imaging features and parametric characteristics.

Aim: Evaluation of role of supplementation of omega-3 polyunsaturated fatty acids on endothelial function in patients with metabolic syndrome. Methods: Total of 80 patients with metabolic syndrome were enrolled to two groups. We evaluated endothelial function in subjects before and after three-month treatment with omega-3 polyunsaturated fatty acids in dose 2.4g daily (800mg 3 times a day) vs placebo. Using the Endo-PAT2000 device (Itamar Medical Ltd. Caesarea, Israel), reactive hyperemia index – a parameter of endothelial function and augmentation index– a parameter of arterial stiffness were measured. Plasmatic level of glutation peroxidase, homocysteine, apolipoprotein B and lipoprotein (a) were also evaluated. Results: The average values of reactive hyperemia index before the treatment with n-3PUFA was 1.62 ± 0.42 , whereas 1.96 ± 0.62 at the end of the study (p<0.005). Augmentation index changed from 14.66 ± 19.55 to 9.21 ± 15.64 after the treatment (p=0.003). We also observed statistically significant decrease of apolipopotein B (0.94 ± 0.36 vs 1.13 ± 0.35, p = 0.001) and homocysteine (19.31 ± 5.29 vs. 13.78 ± 3.05, p = 0.001) and increase of the glutathion perxidase plasma levels (41.65 ± 8.90 vs. 45.20 ± 8.01), p=0.001. Conclusion: We have observed significant improvement of the endothelial function in subjects with metabolic syndrome treated with omega-3 polyunsaturated fatty acids in dose 2.4g daily.

Gastric cancer is an aggressive disease with increasing global incidence in recent years. Human epidermal growth receptor 2 (HER2) is overexpressed in approximately 10-20% of gastric cancers. The implementation of targeted therapy against HER2 as part of the standard of care treatment in metastatic disease has improved the prognosis of this subset of patients. However, gastric cancer still has high mortality rates and urgently requires new treatment strategies. The combination of immunotherapy with HER2-targeted therapies has shown synergistic effects in preclinical models, being the rationale behind exploring this combination in clinical trials in locally advanced and metastatic settings. Additionally, the irruption of antibody-drug conjugates and other novel HER2-targeted agents has led to the development of numerous clinical trials showing promising results. This review presents the molecular mechanisms supporting the use of HER2-targeted drugs in combination with immunotherapy and provides an overview of the therapeutic scenario of HER2-positive disease. We focus on the role of immunotherapy but also summarize emerging therapies and combinations under clinical research that may change the standard treatment in HER-2 positive disease in the future.

This study addresses the pressing need for flood extent and exposure information in data-scarce and vulnerable regions, with a specific focus on West Africa, particularly Senegal. Leveraging the Google Earth Engine (GEE) platform and integrating data from Sentinel-1 SAR, Global Surface Water, HydroSHEDS, Global Human Layer Settlement, and MODIS Land Cover, our primary ob-jective is to delineate flood extents and compare them with centennial flood-prone areas, offering a comprehensive assessment of exposure during the period from July to October 2022 across Sen-egal's 14 regions. The findings underscore a total inundation area of 2 951 square kilometers, impacting 297 142 people, 175 square kilometers of urban and 16 square kilometers of crops. Notably, August wit-nessed the largest flooded areas, reaching 780 square kilometers, constituting 0.40% of the coun-try's surface. Subsequent regions, including Saint-Louis, Ziguinchor, Fatick, and Matam, experi-enced varying extents of flooding, with August data showing a 1.34% overall overlap compared to centennial flood-prone areas derived from hydrological and hydraulic modeling. This low per-centage reveals the distinct purposes and natures of the two approaches (remote sensing and modeling), as well as their complementarity. Turning to flood exposure, August emerges as the most critical month, affecting 76 595 people (0.43% of the total population). Dakar, Diourbel, Thiès, and Saint-Louis regions bore substantial impacts, affecting 100 707, 57 648, 31 579, and 26 581 people, respectively. These findings emphasize the imperative for comprehensive disaster preparedness and mitigation efforts. The study provides a crucial national-scale perspective to guide Senegal's authorities in formulating effective flood management, intervention, and adaptation strategies.

A 2-year prospective study carried out on ventilator-associated pneumonia (VAP) patients in the intensive care unit at King Khalid hospital, Hail, Kingdom of Saudi Arabia (KSA), revealed a high prevalence of extremely drug-resistant (XDR) Acinetobacter baumannii. About a 9% increase in the incidence rate of A. baumannii has occurred in the VAP patients between 2019 and 2020 (21.4% to 30.7%). In 2019 the isolates were positive for IMP-1 and VIM-2 (31.1% and 25.7%, respectively) as detected by PCR. In comparison, a higher proportion of isolates produced NDM-1 in 2020. Here, we observed a high resistant proportion of ICU isolates towards the most common antibiotics in use. Colistin sensitivity dropped to 91.4% in the year 2020 as compared to 2019 (100%). Thus, the finding of this study has a highly significant clinical implementation in the clinical management strategies for VAP patients. Furthermore, strict implementation of antibiotic stewardship policies, regular surveillance programs for antimicrobial resistance monitoring, and screening for genes encoding drug resistance phenotypes have become imperative.

Type 2 diabetes mellitus (T2D) is a metabolic disorder characterized by inappropriate insulin function. Despite wide progress in genome studies, defects in gene expression for diabetes prognosis still incompletely identified. Prolonged hyperglycemia activates NF-κB, which is a main player in vascular dysfunctions of diabetes. Activated NF-κB, triggers expression of various genes that promote inflammation and cell adhesion process. Alteration of pro-inflammatory and profibrotic gene expression contribute to the irreversible functional and structural changes in the kidney resulting in diabetic nephropathy (DN). To identify the effect of some important NF-κB related genes on mediation of DN progression, we divided our candidate genes on the basis of their function exerted in bloodstream into three categories (Proinflammatory; NF-κB, IL-1B, IL-6, TNF-α and VEGF); (Profibrotic; FN, ICAM-1, VCAM-1) and (Proliferative; MAPK-1 and EGF). We analyzed their expression profile in leukocytes of patients and explored their correlation to diabetic kidney injury features. Our data revealed the overexpression of both proinflammatory and profibrotic genes in DN group when compared to T2D group and were associated positively with each other in DN group indicating their possible role in DN progression. In DN patients, increased expression of proinflammatory genes correlated positively with glycemic control and inflammatory markers indicating their role in DN progression. Our data revealed that the persistent activation NF-κB and its related genes observed in hyperglycemia might contribute to DN progression and might be a good diagnostic and therapeutic target for DN progression. Large-scale studies are needed to evaluate the potential of these molecules to serve as disease biomarkers.

Synthesis and antitumour activity of a palladium compound, [Bis (quinoline) palladium (II) chloride] (coded as NH1) alone and in combination along with its proposed mechanism of action has been described in the present study. Antitumour activity has been performed in seven different cancer cell lines using colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The investigated palladium compound demonstrated superiority over clinical standard cisplatin against drug resistant ovarian cancer cell lines. NH1 also demonstrates 4.4 times greater activity than cisplatin against breast cancer model. Binary sequenced combination study showed that NH1 in combination with curcumin is mostly additive to antagonistic. However, combination of NH1 with 6-shogaol demonstrated synergism depending on dose and sequence. Proteomic study revealed that changes in expression of 14 proteins were significantly associated with anticancer mechanism of NH1. In vivo anticancer activity of NH1 at a dose of 0.75 mg/kg was also evaluated using Erlich Ascites Carcinoma (EAC) cell lines in Swiss-albino mice model. Preliminary toxicity study in Swiss-albino mice proved that NH1 is comparatively less toxic at both of the administered doses, either 2.5 mg/kg or 5 mg/kg. However, cisplatin demonstrated significant toxicity at both of the administered doses. Biochemical investigations also supported that NH1 demonstrated lesser toxicity profile towards liver or kidney compared to clinical standard cisplatin.

The anodic polarization response of magnesium alloy AZ31 was characterized during exposure to aerated 0.1M NaCl solutions with millimolar additions of NaVO₃, Na₃PO₄, Na₂HPO₄, NaF and various pairings to assess their ability to inhibit corrosion kinetics and retard localized corrosion. Each of the candidate inhibitors reduced the corrosion rate of the alloy to some degree. A Na₃PO₄ - NaVO₃ pair produced a powerful inhibiting response decreasing the corrosion rate to about 10^-7 A/cm², which was two orders of magnitude lower than the uninhibited control case. A Bliss Independence assessment indicated that this inhibitor pair acted synergistically. A Na₂HPO₄ - NaVO₃ pair reduced the corrosion rate to 10^-6 A/cm² but was not assessed to be acting synergistically. The NaVO₃ - NaF pair did not reduce the corrosion rate significantly compared to the control case and was an antagonistic pairing. SEM imaging showed film formation due to exposure, which appears to be the origins of the observed inhibition. The resistance to localized corrosion was assessed as the difference in the breakdown potential and the corrosion potential with larger values indicating a lower probability of localized corrosion during free corrosion exposures. Effects of the inhibitors on this characteristic were mixed, but each of the inhibitor pairs yielded potential differences in excess of 100mV. A conceptual conversion coating process based on a mixture of vanadate and phosphate compounds were demonstrated. A fluoride-bearing formulation produced coatings whose total impedance was increased by a factor or 2 compared to an uncoated control. A fluoride-free formulation produced coatings whose corrosion resistance was increased by more than a factor of 3.

O26 enteropathogenic Escherichia coli (EPEC), possesses a unique pseudocapsule composed of polysaccharides identical to the O antigen in their lipopolysaccharide (LPS) membrane. Therefore, the impact of O26 polysaccharides on the immune evasion mechanisms of capsulated O26 EPEC was investigated. Our findings reveal that the concentration of GlcNAc, an immunodominant unit of O26 polysaccharides capable of activating the MBL (Mannose Biding Lecting) pathway of the complement system, was found to be lower in capsulated EPEC O26 compared to naked shiga toxin-producing E. coli (STEC) O26 strain. It was noted that, unlike the naked STEC strain, the capsulated EPEC O26 strain was protected against lysis by the alternative pathway of the com-plement system by inhibiting C3b adhesion to its bacterial surface. Capsulated EPEC O26 strains were also able to avoid phagocytosis by macrophages. However, the immune evasion provided by the capsule was overcome in the presence of anti-O26 polysaccharide antibodies. Additionally, these antibodies were able to recognize O26 EPEC in the presence of biofilm and inhibit their adhesion to human epithelial cells. Overall, the results indicate that the O26 polysaccharides can generate an effective humoral immune response, making them promising antigens for the de-velopment of a vaccine against capsulated O26 E. coli

Due to the growing interest in biopolymers, biosynthesizable and biodegradable polymers currently occupy a special place. Unfortunately, the properties of native biopolymers are not satisfactory, which explain that attempts are being made to modify them. The work attempts to improve the properties of poly(3-hydroxybutyrate) (P3HB) using linear aliphatic polyurethane (PU) based on 1,4-butanediol and hexamethylene 1,6-diisocyanate. The conducted studies on the effect of the amount of PU used (5, 10, 15 and 20 wt.%) showed an improvement in the thermal properties of the prepared polymer blends. There was an increase in the degradation temperature of the ob-tained blends in relation to the native P3HB by 12-57C, and the difference between the melting point and the degradation point was above 100°C for most of the obtained blends. As part of the tested mechanical properties of the new polymer blends, we noted the desired increase in the tensile strength, in the relative elongation at break and in the impact strength with a decrease in hardness, in particular with the presence of 5 wt.% PU. Therefore, for further improvement, hybrid nanobiocomposites with 5 wt.% PU and organically modified montmorillonite (MMT – Cloisite 30B) were produced. The nanoadditive was used in typical amount of 1-3 wt.%. The nanostructure of the biocomposites produced by extrusion was examined by small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM), the morphology by scanning electron microscopy (SEM), and compatibility by infrared spectroscopy (FT IR). In addition, selected mechanical properties were determined and thermal properties were tested by the thermogravimetric analysis (TGA) and the standard differential scanning calorimetry (DSC). The polyester and polyurethane chains penetrated into the interlayer spaces of organically modi-fied nanoclay – Cloisite30B and the complete delamination occurred during direct mixing in the extrusion process. FT IR spectral analysis showed the compatibility of the polymer biocomposite components by the coexistence of intermolecular interactions in the form of hydrogen bonds. The morphology studies of the produced hybrid nanobiocomposites showed an interaction of the bi-opolymer matrix with PU and Cloisite30B and the formation of easily migrating polyester-polyurethane-montmorillonite adducts, which resulted in improved mechanical properties com-pared to the properties of the native P3HB and P3HB-PU compositions. The influence of the presence of a nanofiller on the properties of the prepared nanobiocomposites was tested and it was found that, as expected, the smallest amount of nanofiller provides the best results.It was found that the obtained nanobiocomposites containing the smallest amount of nano-fillers, i.e. 1 wt.% Cloisite30B exhibited the best mechanical and thermal properties. The desired decrease in hardness by 15% and a higher value of impact strength by 15%, an increase in elonga-tion at break by 60% and an increase in thermal stability of the newly produced biocomposites compared to to the native P3HB were observed. The prepared nanobiocomposites combined the best features caused by the elasticizing effect of polyurethane and the formation of P3HB-PU-MMT adducts.

Some aporphine alkaloids, such as crebanine, were found to present arrhythmic activity and also higher toxicity. A series of derivatives were synthesized by using three kinds of aporphine alkaloids (crebanine, isocorydine, and stephanine) as lead compounds. Chemical methods, including ring-opening reaction, bromination, methylation, acetylation, quaternization, and dehydrogenation, were adopted. Nineteen target derivatives were evaluated for their antiarrhythmic potential in the mouse model of ventricular fibrillation (VF), induced by CHCl₃, and five of the derivatives were investigated further in the rat model of arrhythmia, induced by BaCl₂. Meanwhile, preliminary structure-activity/toxicity relationship analyses were carried out. Significantly, N-acetamidesecocrebanine (1d), three bromo-substituted products of crebanine (2a, 2b, 2c), N-methylcrebanine (2d), and dehydrostephanine (4a) displayedantiarrhythmic effects in the CHCl₃-induced model. Among them, 7.5 mg/kg of 2b was able to significantly reduce the incidence of VF induced by CHCl₃ (p<0.05), increase the number of rats that resumed sinus rhythm from arrhythmia, induced by BaCl₂ (p<0.01), and the number of rats that maintained sinus rhythm for more than 20 minutes (p<0.01). Therefore, 2b showed remarkably higher antiarrhythmic activity and a lower toxicity (LD₅₀=59.62 mg/kg, mice), simultaneously, indicating that 2b could be considered as a promising candidate in the treatment of arrhythmia. Structural-activity analysis suggested that variationsin antiarrhythmic efficacy and toxicity of aporphines were related to the C-1,C-2-methylenedioxy group on ring A, restricted ring B structural conformation, N-quaternization of ring B, levoduction of 6a in ring C, and the 8-, 9-, 10-methoxy groups on ring D on the skeleton.

Nitriding has long been used to engineer the surfaces of engineering steels to improve their surface and subsurface properties. The role of the surface compound layer (’-Fe4N and/or -Fe2-3N) in improving the tribological and corrosion resistant properties of nitrided steels has been established. However, there have been very few studies on the response of the compound layer to tribocorrosion in corrosive environments. In this work, the tribocorrosion behaviour of a 5 m thick ’-Fe4N nitride layer produced on mild steel (MS) by plasma nitriding has been studied in a NaCl containing solution under various electrochemical conditions. The results show that at a cathodic potential, where mechanical wear is predominant, the total material removal (TMR) from the ’-Fe4N layer is 37% smaller than that from the untreated MS, and at open circuit potential, TMR from the layer is 35% smaller than that from the untreated MS, while at an anodic potential, the ’-Fe4N layer can reduce TMR from mild steel by 87%. The beneficial effect of the ’-Fe4N nitride layer in improving the tribocorrosion behaviour of mild steel is derived from its high hardness and good corrosion resistance in the test solution and its ability to resist both mechanical wear and chemical wear.

Molten salt reactors have gained substantial interest in the last years due to their flexibility and their potential for simplified closed fuel cycle operation for massive net-zero energy production. However, a zero-power reactor experiment will be an essential first step into the process delivering this technology. The choice of the optimal reflector material is one of the key issues for such experiments since on the one hand it offers huge cost saving potential due to reduced fuel demand, on the other hand an improper choice of the reflector material can have negative effects on the quality of the experiments. The choice of the reflector material is for the first time introduced through a literature review and a discussion of potential roles of the reflector. The 2D study of different potential reflector materials has delivered a first down selection with SS 304 as representative for stainless steel, lead, copper, graphite, and beryllium oxide. A deeper look identified in addition iron-based material with high Si content. The following evaluation of the power distribution has shown the strong influence of the moderating reflectors creating a massively disturbed power distribution with a peak at the core boundary. This effect has been confirmed through a deeper analysis of the 2D multi-group flux distribution which lead to the exclusion of the BeO and the graphite reflector. The most promising materials identified have been SS 304, lead, and copper. The final 3D Monte-Carlo study demonstrated that all three materials have the potential to reduce the required amount of fuel by up to 60% compared NaCl which has been used in previous studies and is now taken as reference A first cost analysis has identified the SS 304 reflector as the most attractive solution. The results of the 2D multi group deterministic study and the 3D multi group Monte-Carlo study have been confirmed through a continuous energy Monte-Carlo reference calculation showing only minor differences.

Our environment has been significantly impacted by man-made pollutants, primarily due to industries make substantial use of synthetic chemicals, resulting in significant environmental consequences. In this research investigation, the co-precipitation approach was employed for the synthesis of cellulose-based ferric oxide (Fe₂O₃/cellulose) and copper oxide nanoparticles (CuOx-NPs). Scanning electron microscopy (SEM) analyses were conducted to determine the properties of the newly synthesised nanoparticles. Furthermore, the synthesized nanoparticles were employed for eliminating chromium from aqueous media under various conditions, including temperature, contact time, adsorbent concentration, adsorbate concentration, and pH. Additionally, the synthesised materials were used to recover Cr(VI) ions from real samples, including tap water, seawater, and industrial water, and the adsorptive capacity of both materials evaluated under optimal conditions. The synthesis of Fe₂O₃/cellulose and CuOx-NPs proved to be effective, as indicated by the outcomes of the study.

The prevalent pathogens associated with bovine uterine infections are bacteria that appear to increase the host's susceptibility to secondary infections with other bacteria or viruses, among which BoHV-4 is the most frequently found. In this work, the study of the pathways of apoptosis induction was carried out on an experimental model of primary culture of endometrial cells, in order to know the implication of BoHV-4 and the presence of bacterial LPS in the pathogenesis of the bovine reproductive tract. For this, different staining techniques and molecular analysis by RT-PCR were used. The results obtained allowed us to conclude that the level of cell death observed in the proposed primary culture is directly related to the time of viral infection and the presence of LPS in BoHV-4 infection. The apoptosis indices in cells infected with BoHV-4, BoHV-4 + LPS presented a maximum that correlates with the appearance of the cytopathic effect, and the maximum viral titers in the model studied. However, morphological, biochemical and molecular changes were evident during both early and late stages of apoptosis. These findings provide information on the factors that may influence the pathogenesis of BoHV-4 and help to better understand the mechanisms involved in virus infection.

The major auxin, indole-3-acetic acid (IAA), is associated with a plethora of growth and developmental processes including embryo development, expansion growth, cambial activity, and the induction of lateral root growth. Accumulation of the auxin precursor indole-3-acetamide (IAM) induces stress related processes by stimulating abscisic acid (ABA) biosynthesis. How IAM signaling is controlled is, at present, unclear. Here, we characterize an ami1/rooty double mutant, that we initially generated to study the metabolic and phenotypic consequences of a genetic blockade of the indole glucosinolate and IAM pathways in Arabidopsis thaliana. Our mass spectrometric analyses of the mutant revealed that the combination of the two mutations is not sufficient to fully prevent the conversion of IAM to IAA. The detected strong accumulation of IAM was, however, recognized to substantially impair seed development. We further show by genome-wide expression studies that the double mutant is broadly affected in its translational capacity, and that a small number of cell proliferation and plant growth regulating transcriptional circuits are repressed by the high IAM content in the seed. In accordance with the previously described growth reduction in response to elevated IAM levels, our data support the hypothesis that IAM is a growth repressing counterpart to IAA.

Although conventional chemotherapeutic drugs are the first line of treatment for cancer, they have numerous side effects. One of the emerging challenges in cancer treatment is drug resistance. Nat-ural compounds have proven effective against various hallmarks of cancer for their multi-target inhibition properties, but especially for their ability to synergistically bypass low bioavailability. Methods: The present study investigated the in vivo antitumor effects of a combination of two natural dietary agents, epigallocatechin-3-gallate (EGCG) from Camelia Sinensis and curcumin, a component of turmeric (Curcuma longa). We aimed to compare, for the first time in vivo, the antiangiogenic and antitumor effects of sunitinib with the combination of curcumin and EGCG in a mouse model of renal cell carcinoma (ccRCC). It was shown that they are able to inhibit cell survival, proliferation of several type of cancer, including renal cell carcinoma (ccRCC), by mod-ulating different signaling pathways and that their combination respect to single compound syn-ergistically decreased angiogenesis. Results: Herein, we highlighted that these compounds inhib-ited the growth of xenografted renal cancer in nude mice by significant inhibition of tumor vol-ume, tumor weight and CD31 expression with no signs of hepatic toxicity. Moreover, mice treated with these natural compounds showed a significant reduction in angiogenesis and an improve-ment in survival rate with p<0.05. Finally, pretreatment of mice with a diet containing 0.6% curcumin before injection of tumor cells showed a significant inhibition of tumor engraftment in 60% of mice with respect to controls and other groups. Conclusions: Taken together, our data in-dicate, for the first time, that the combination of curcumin and EGCG acts in a synergistic manner to inhibit the growth and angiogenesis of ccRCC and with less toxicity than sunitinib and provide an important rationale for future clinical development for chemoprevention and treatment of re-nal cancer.

Large-scale genetic studies have identified numerous genetic risk factors that suggest a central role for innate immune cells in susceptibility to Alzheimer’s disease (AD). CD33, an immunomodulatory transmembrane sialic-acid binding protein expressed on myeloid cells, was identified as one such genetic risk factor associated with Alzheimer’s disease. Several studies explored the molecular outcomes of genetic variation at the CD33 locus. It has been determined that the risk variant associated with AD increases the expression of the large isoform of CD33 (CD33M) in innate immune cells and alters its biological functions. CD33 is thought to signal via the interaction of its ITIM domain and the protein tyrosine phosphatase, SHP-1. Here, we utilize different molecular and computational approaches to investigate how AD-associated genetic variation in CD33 affects its interaction with SHP-1 in human microglia and microglia-like cells. Our findings demonstrate a genotype-dependent interaction between CD33 and SHP-1, which may functionally contribute to the AD risk associated with this CD33 variant. We also found that gene-gene interactions impact AD-related traits.

Infection by human immunodeficiency virus type I (HIV-1) requires virus particle binding to host cell-surface receptor CD4 via the viral envelope glycoprotein gp120. HIV-1 therapy and prevention efforts involve development of mimetic or recombinant gp120 vaccines or deployment of antiviral agents that target specific epitopes of gp120. The unliganded conformational state of gp120 is closed, whereas the CD4-bound state is open. However, in between, there exist dynamic conformational states, indicating intrinsically flexible region(s) of structural dynamics, imposing a structural challenge for developing drug or antibody targets. Known conformational states of gp120 were determined by X-ray crystallographic and cryo-electron microscopy, and neither method captures the population of gp120 species arising from conformational plasticity, motions, and transitions. gp120 plasticity brings up several important questions. How will differences in conformation affect receptor binding, antibody recognition, and neutralization? Which regions are crucial for gp120 structural plasticity? How could structural dynamics influence HIV-1 evasiveness against host immunity and drugs or vaccines, and facilitate the viral entry into its host? This review explores the structural constraints presented by conformational states of the glycoprotein to antibodies or drugs and how these conformational states provide structural avenues for the virus to escape neutralizing agents and evade host immunity.

After a long limbo, RNA has gained its credibility as a druggable target, fully earning its de-served role in the next-generation area of pharmaceutical R&D. We have recently probed the Trans-Activation Response element (TAR), a RNA stem–bulge–loop domain of the HIV-1 genome with bis-3-chloropiperidines (B-CePs), and revealed the compounds unique behavior in stabiliz-ing TAR structure, thus impairing in vitro the chaperone activity of the HIV-1 nucleocapsid (NC) protein. Seeking to elucidate the determinants of B-CePs inhibition, we have further characterized here their effects on the target TAR and its NC recognition, while developing quantitative analyti-cal approaches for the study of multicomponent RNA-based interactions.

Satellite altimeters have been used to monitor river and reservoir water levels, from which water storage estimates can be derived. Inland water altimetry can therefore play an important role in continental water resource management. Traditionally, satellite altimeters were designed to monitor homogeneous surfaces such as oceans or ice sheets, resulting in a poor performance over small inland water bodies due to the contribution from land contamination in the returned waveforms. The advent of synthetic aperture radar (SAR) altimetry (with its improved along-track spatial resolution) has enabled the measurement of inland water levels with a better accuracy and an increased spatial resolution. This paper presents three specialized algorithms or retrackers to retrieve water levels from SAR altimeter data over inland water bodies dedicated to minimizing land contamination from the waveforms. The performances of the proposed waveform portion selection method with three retrackers, namely, the threshold retracker, Offset Centre of Gravity (OCOG) retracker and 2-step physical-based retracker, are compared. Time series of water levels are retrieved for water bodies in the Ebro River basin (Spain). The results show good agreement with in situ measurements from the Ebro Reservoir (width is approximately 1.8 km) and Ribarroja Reservoir (width is approximately 400 m) with un-biased root-mean-square errors (RMSEs) of approximately 0.28 m and 0.16 m, respectively. The performances of all three retrackers are also compared with the European Space Agency’s ocean retracker in the Sentinel-3 Level-2 product.

Background Olfactory perception is an important physiological function for the human well-being and health. Loss of olfaction, or anosmia, caused by viral infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) received a considerable attention especially in the persistent cases that take long time to recover. Objectives This review discusses the integration of different components of the olfactory epithelium to serve as a structural and functional unit, and explores how they are affected during viral infections, leading to the development of olfactory dysfunction. Methods The review mainly focused on the role of receptors mediating the disruption of olfactory signal transduction pathways such as ACE2, TMPRSS2 protease, neuropilin 1 (NRP1), basigin (CD147), olfactory, TRPV1, purinergic, and interferon gamma receptors. Furthermore, the compromised function of the epithelial sodium channel (ENaC) induced by SARS-CoV-2 infection and its contribution in olfactory dysfunction is also discussed. Results Collectively, this review provides fundamental information about the many types of receptors that may modulate olfaction and participate in olfactory dysfunction. It will help to understand the underlying pathophysiology of virus-induced anosmia which may help in finding and designing effective therapies targeting molecules involved in viral invasion and in olfaction. Conclusion This wide and complex spectrum of receptors that mediates the pathophysiology of olfactory dysfunction reflects the many ways by which anosmia can be therapeutically managed.

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.

Current neural network models can demonstrate reasonable-looking behavior, considered by some developers and researchers human-like. For example, a large language model GPT-3 is susceptible to human-like cognitive biases. Yet there is no data of such models solving emotional intelligence (EI) tasks. They are connected to the abilities that has been previously considered as specifically human EI is an important aspect of human communication. The ability to understand and respond to emotional cues is essential for effective communication. Therefore, it is crucial to determine the ways AI models such as ChatGPT demonstrate EI. The present research aims to measure the EI of GPT-4, a large language model trained by OpenAI. Russian version of the Mayer–Salovey–Caruzo Emotional Intelligence Test sections B, C, D, F, G and H were used in this research. High points were obtained in Understanding emotions scale and Strategic EI. Mean points are obtained in Managing emotions scale. Low and less reliable values are obtained in Using emotions to facilitate thought scale. Thus, GPT-4 seems already capable of identifying emotions in text and describing techniques for managing them. However, complex cases and irregular situations requiring emotions qualitative analysis would be a hard task for GPT-4.

This perspective discusses the ongoing real-world practice using nitazxoanide, NSAIDs and/or azithromycin (Kelleni’s protocol) to manage the evolving manifestations of SARS CoV-2 Omicron EG.5.1, its descendant HV.1 as well as BA.2.86 and its descendant JN.1 subvariants in Egypt. These subvariants are well-known for their highly evolved immune-evasive properties and the manifestations include some peculiar manifestations as persistent cough besides high fever in young children as well as high fever, persistent severe cough, change of voice, loss of taste and smell, epigastric pain, nausea, vomiting, diarrhea, generalized malaise and marked bone aches in adults including the high risk groups. It’s suggested that the ongoing SARS CoV-2 evolution is continuing to mostly affect the high risk groups of patients, to some of whom we’ve also successfully prescribed nitazoxanide and/or NSAIDs for post-exposure prophylaxis of all household contacts. We also continue to recommend starting the immune-modulatory antiviral Kelleni’s protocol as soon as possible in the course of infection and adjusting it in a personalized manner to be more aggressive from the beginning for the high risk patients, at least until the currently encountered surge of infections subsides.

It is discovered that writing an odd integer as $2^m - 1$ for $m \geq 1$ helps in understanding the dynamics of the Collatz-type sequences. Starting with the original Collatz sequence $3n + 1$, it is found that when the odd step is applied to an odd integer $2^m - 1$, an even integer $2^{m+1} + 2^m - 2$ is obtained, which is exactly once divisible by 2. This implies that the sequence alternates between odd and even steps $m$ times. This governs the dynamics of the Collatz-type sequences because: (i) for the sequence to diverge to infinity, $m$ must be infinite, and (ii) the value of $m$ determines the number of times the integer can be divided by 2 in each even step. This formulation allows construction of odd integers like $\sum 2^m - 1$ to follow specific patterns of odd and even steps. Applying this understanding to the modified Collatz sequence $5n + 1$ reveals that for $m = 3$, the integer $2^{m + 1} + 2^m - 1$ is obtained, indicating that any integer formulation ending with $2^3 - 1$ in $5n + 1$ will diverge to infinity.

Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research pro-gresses in the effect of bacterial dysbiosis from a metabolic point of view, particularly on the bio-chemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with an-ti-inflammatory and anti-tumor properties in CRC. Increased daily intake of omega-3 polyun-saturated fatty acids (PUFAs) significantly increases the density of bacteria that are known to produce butyrate. Omega-3 PUFAs have been proposed as a treatment to prevent gut microbiota dysregulation and lower the risk or progression of CRC.

Trigonella foenum is one of the oldest medicinal plants that grow in many parts of Iran with the diverse ecological situation. Employing this plant for treating diabetes and high cholesterol has a long history, because of some metabolites. Due to the habitat of fenugreek is a wide range of climatic conditions, it may have power to cope with climate variation. The main intention of this inquiry was to understand the effect of the environmental variables on this therapeutic plant features. It was also interesting for us to understand which environment variables are more impressive for enhancing of trigonelline and 4-hydroxy isoleucine content as the most important metabolites of this plant. For achieving this goal, environmental information and vegetal data were analyzed to discover the role of nature on the seed part of fenugreek life in 50 different regions of Iran. Canonical correspondence analysis (CCA) displayed that high content of metabolites and some morphological characteristics happened in high temperature and solar irradiation. Partial least squares regression (PLSR) and path analysis used to find the best predictors and direct and indirect effect of all variables on 4-hydroxy isoleucine and trigonelline. Ecological condition were the best predictors and had the highest direct and indirect impact on 4-hydroxy isoleucine. However, for trigonelline, the environment did not play a senior role. It seems that the reaction of components of fenugreek does not follow the same way. Studying on morphological, primary and secondary metabolites, and surrounding environment of fenugreek, helped us to have a more precise judgment about the life of this plant.

(1) Background: The aim of this study was to analyze the relationship between the serum levels of soluble transferrin receptor (sTfR) and interleukin 4 (IL-4), and disease activity and organ mani-festations in SLE patients. (2) Methods: We studied 200 SLE patients and 50 controls. We analyzed disease activity, organ involvement, serum sTfR, IL-4, and interleukin-6 (IL-6) levels, and antinu-clear and antiphospholipid antibody profiles. (3) Results: The median serum levels of sTfR (p>0.000001) and IL-4 (p<0.00001) were higher in the study group than in the controls. SLE patients, compared to the controls, had significantly lower HGB levels (p<0.0001), a lower iron concentration (p=0.008), a lower value of total iron-binding capacity (TIBC) (p=0.03), and lower counts of RBC (p=0.004), HCT (p=0.0004), PLT (p=0.04), neutrophil (p=0.04), and lymphocyte (p<0.0001). Serum sTfR levels were negatively correlated with lymphocyte (p=0.0005), HGB (p=0.0001) and HCT (p=0.008), and positively correlated with IL-4 (p=0.01). Elevated serum sTfR >2.14 mg/dL was associated with an increased risk of myocardial infarction (OR: 10.6 95 CI 2.71–464.78; p=0.001), ischemic heart disease (OR: 3.25 95 CI 1.02–10.40; p=0.04), lung manifestations (OR: 4.48 95 CI 1.44–13.94; p=0.01), and hematological manifestations (OR: 2.07 95 CI 1.13–3.79; p=0.01), and with a reduced risk of neuropsychiatric manifestations (OR: 0.42 95 CI 0.22–0.80; p=0.008). Serum IL-4 was negatively correlated with CRP (p=0.003), and elevated serum IL-4 levels > 0.17 mg/l were associated with a reduced risk of mucocutaneous manifestations (OR: 0.48 95 CI 0.26–0.90; p=0.02). (4) Conclusions: In SLE patients, elevated serum levels of sTfR were associated with an increased risk of cardiovascular, pulmonary, and hematological manifestations, and with a decreased risk of neuropsychiatric manifestations. In contrast, elevated serum IL-4 levels were associated with a decreased risk of mucocutaneous manifestations.

It has been long recognized that under hypoxia conditions cancer cells reprogram their metabolism through shift from oxidative phosphorylation (OXPHOS) to glycolysis to meet elevated requirements in energy and nutrients for proliferation, migration and survival. However, data accumulated over the last years increasingly evidence that cancer cells can revert from glycolysis to OXPHOS and maintain both reprogrammed and oxidative metabolism even in the same tumor. The phenomenon denoted as cancer cell metabolic plasticity or hybrid metabolism depends on a tumor micro-environment, which is highly heterogeneous and influenced by intensity of vasculature and blood flow, oxygen concentration, nutrient and energy supply, and requires regulatory interplay between multiple oncogenes, transcription factors, growth factors, reactive oxygen species (ROS), etc. Hypoxia-inducible factor-1 (HIF-1) and AMP-activated protein kinase (AMPK) represent key modulators of switch between reprogrammed and oxidative metabolism. The present review focuses on cross-talks between HIF-1, GLUTs, and AMPK and other regulatory proteins including oncogenes such as c-Myc, p53 and KRAS, growth factor-initiated PKB/Akt, PI3K and mTOR signaling pathways and tumor suppressors such as LKB1 and TSC1 in controlling cancer cell metabolism. The multiple switches between metabolic pathways can underlie chemo-resistance to conventional anti-cancer therapy and should be taken into account in choosing molecular targets to discovery novel anti-cancer drugs.

This article utilized electrodeposition technology to fabricate Zn and Zn-Y₂O₃-Al₂O₃ composite coatings on Q235 steel plates. The composite coatings were obtained by adding Y₂O₃/Al₂O₃ nanoparticles (0, 5, 10, and 15 g/L) to acidic chloride solutions. This study then examined the impact of these nanoparticles on the microstructure, morphology, microhardness, hydrophobicity, and corrosion resistance of the composite coatings. The results indicate that the addition of the nanoparticles increased the nucleation sites on the surface of the coating, thereby refining the grain size and reducing the roughness of the coating surface. When 10g/L of Y₂O₃ and 10g/L of Al₂O₃ nanoparticles were added, the hardness of the composite coating (369 Hv) was 2.49 times higher than that of the pure Zn coating (148 Hv), which was attributed to the dispersion strengthening and grain refinement effects of the nanoparticles. The corrosion resistance of the Zn and Zn-Y₂O₃-Al₂O₃ composite coatings was studied using linear sweep voltammetry and AC impedance spectroscopy. The addition of the nanoparticles improved the corrosion resistance of the composite coating, and the composite coating prepared in an electrolyte containing 10 g/L of Y₂O₃ and 10 g/L of Al₂O₃ nanoparticles exhibited the best corrosion resistance. Meanwhile, the composite coating exhibited good hydrophobicity, with a contact angle of 120.9°, 1.94 times that of the pure Zn coating (62.2°). The Zn-Y₂O₃-Al₂O₃ nanocomposite coating material has significant potential advantages in the field of steel corrosion.

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.

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a human DNA repair protein. It is a member of the phospholipase D family based on the structure similarity. TDP1 is a key enzyme involved in repairing stalled topoisomerase 1 (TOP1)-DNA complexes. Previously we obtained with the CRISPR/Cas9 method HEK293A cells with the homozygous knockout of the Tdp1 gene and used knockout cells as a cellular model for studying the mechanisms of anticancer therapy. In this work we studied for the first time by transcriptomic analysis the effect of Tdp1 gene knockout on genes expression changes in human HEK293A cell line. We received original data that may indicate a role of TDP1 in other process besides repair of DNA-TOP1 complex. The differentially expressed genes (DEGs) analysis revealed that TDP1 could be involved in different processes such as cell adhesion and communication, spermatogenesis, mitochondrial function, neurodegeneration, cytokine response, and MAPK pathway signaling.

We describe an efficient and cost effective data access mechanism for Sentinel-1 TOPS 1 mode bursts. Our data access mechanism enables burst-based data access and processing, thereby 2 eliminating ESA’s Sentinel-1 SLC data packaging conventions as a bottleneck to large scale processing. 3 Pipeline throughput is now determined by available compute resources and efficiency of the analysis 4 algorithms. For targeted infrastructure monitoring studies, we are able to generate coregistered, 5 geocoded stacks of SLCs for any AOI in the world in a few minutes. In addition, we describe our 6 global scale radar backscatter and interferometric products and associated pipeline design decisions 7 that ensure geolocation consistency across the suite of derived products from Sentinel-1 data. Finally, 8 we discuss the benefits and limitations of working with geocoded SAR SLC data.

To understand the biological relevance and mode of action of artificial protein ligands, crystal structures with their protein targets are essential. Here, we describe and investigate all known crystal structures that contain a so-called “molecular tweezer” or one of its derivatives with an attached natural ligand on the respective target protein. The aromatic ring system of these compounds is able to include lysine and arginine side chains, supported by one or two phosphate groups that are attached to the half-moon shaped molecule. We analyse the corresponding crystal structures with 14-3-3 proteins in complex with mono- and diphosphate tweezers. Furthermore, we solved crystal structures of two different tweezer variants in complex with the enzyme 1-Pyrroline-5-carboxyl-dehydrogenase (P5CDH), and found that the tweezers are bound to a lysine and methionine side chain, respectively. The different binding modes and their implications for affinity and specificity are discussed, as well as the general problems in crystallizing protein complexes with artificial ligands.

For Interferometry Synthetic Aperture Radar (InSAR), the normal baseline is one of the main factors that affect the accuracy of the ground elevation. For Gaofen-3 (GF-3) InSAR processing, the poor accuracy of the real-time orbit determination resulting in a large baseline error, leads to the modulation error in azimuth and the slope error in range for timely Digital Elevation Model (DEM) generation. In order to address this problem, a baseline estimation method based on external DEM is proposed in this paper. Firstly, according to the characteristic of the real-time orbit of GF-3 images, orbit fitting is executed to remove the non-linear error factor. Secondly, the height errors are obtained in slant-range plane between Shuttle Radar Topography Mission (SRTM) DEM and the GF-3 generated DEM after orbit fitting. At the same time, the height errors are used to estimate the baseline error which has a linear variation. In this way, the orbit error can be calibrated by the estimated baseline error. Finally, DEM generation is performed by using the modified baseline and orbit. This procedure is implemented iteratively to achieve a higher accuracy DEM. Based on the results of GF-3 interferometric SAR data for Hebei, the effectiveness of the proposed algorithm is verified and the accuracy of GF-3 real-time DEM products can be improved extensively.

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 &amp; 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.

Metastasis is a major cause factor for breast cancer (BC)-associated mortality. During the metastatic process, disseminated tumor cells (DTCs) detach from the primary sites, and enter the bloodstream and establish the secondary colonies. Recent studies have provided substantial evidence for the importance of Notch signaling in BC metastasis. Therefore, this review focuses on the mechanisms by which Notch contributes to the origin of BC DTCs, increases their motility, regulates their intravasation and extravasation, protects them from host surveillance, and finally facilitates colonization. Identification of the mechanisms underlying Notch-related BC metastasis will lead to the development of novel Notch-targeted therapeutic strategies to reduce metastasis and significantly improve outcomes.

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.

The historical and cultural use of food as a remedy for diseases is evident in societies, such as using Hibiscus sabdariffa to address conditions like hypertension and high blood glucose. The natural biocompounds in this plant, including Delphinidin-3-Sambubioside (DS3), Quercetin (QRC), and Hibiscus Acid (HA), have been linked to various health benefits. Despite individual attention, molecular targets for these compounds remain unclear. In this study, in-silico analysis employed bioinformatic tools; including Swiss Target Prediction, ShinnyGo 0.77, KEGG, and Stringdb, to identify molecular targets, pathways, and hub genes. A PubMed literature search complemented the results. DS3 demonstrated potential modifications in genes related to nitrogen and glucose metabolism, inflammation, angiogenesis, and cell proliferation, particularly affecting the PI3K-AKT pathway. QRC displayed interconnected targets across multiple pathways, with overlap with DS3 and a focus on cancer-related pathways. HA showed distinct targets, particularly associated with nervous system-related pathways. These findings highlight the need for targeted research on the molecular effects of DS3, QRC, and HA, providing valuable insights into potential therapeutic pathways.

In this research, first a binary nanocomposite of magnetic recyclable photocatalyst Fe₃O₄/TiO₂, was synthesized by sol gel technique. Then, in order to enhance the photocatalytic activity of the synthesized nanocomposite, it was deposited by silver nanoparticles for using in degradation of organic pollutants 2, 4-dichlorophenol (2, 4-DCP) under visible light. A range of analytical techniques including XRD, FESEM/EDX, DRS, VSM and N₂ physisorption were employed to reveal the crystal structure, morphology and property of the nanocomposites. We obtained 32% and 55% degradation of 2, 4-DCP under visible light after 180 min irradiation in the presence of Fe₃O₄/TiO₂ and Fe₃O₄/TiO₂/Ag respectively. Thus, the excellent visible light photocatalytic activity of Fe₃O₄/TiO₂/Ag sample can be attributed to the surface plasmon resonance effect of Ag nanoparticles deposited on Fe₃O₄/TiO₂ nanocomposite.

Nasopharyngeal carcinoma (NPC) has not been thoroughly studied, and the pathogenesis of NPC is unclear. Scientists have neither discovered effective therapies nor achieved a desirable prognosis. Some studies have found that the regulation of intra- and extracellular ion channels hinges directly on cell apoptosis, and treatment with Gambogenic acid (GNA) brings changes to the volume-sensitive outwardly rectifying chloride (VSOR Cl-) current of CNE-2Z cells recorded by the patch clamp method. Nevertheless, rarely have any researchers probed into the relevance between this variation and the anti-tumor mechanism of GNA. This paper is suggested that GNA activates the VSOR Cl- current on the CNE-2Z cell membrane, and the activation of VSOR Cl- currents by GNA in CNE-2Z cells is blocked by the chloride channel blockers DIDS and DCPIB. GNA induces the down-regulation of GRP78 and up-regulation of ATF4 as well as chop proteins, which is evidence for the induction of CNE-2Z cell apoptosis, and this correlates with ER stress. GNA can activate the VSOR Cl- channel and lead to the occurrence of ER stress, thus inducing the apoptosis of CNE-2Z cells and inhibiting the proliferation of CNE-2Z cells.

Ionic liquids (ILs) have gained interest among researchers due to its tunable properties that can be used in wide applications. However, toxicity and bio-degradation studies of ILs proved that most of the aromatic ILs, such as imidazolium is highly toxic and non-biodegradable. Several advance oxidation processes (AOPs) have been investigated by researchers to evaluate the efficiency of the systems for the removal of ILs from wastewater. However, the issue on relative high cost and environmental concern has limited the application of these AOPs in industry. In this research, photocatalytic study using hybrid nano-materials was conducted to evaluate the efficiency of this system as an alternative AOP system for removal of ILs from wastewater. The synergistic effect of adsorption-photodegradation was introduced by depositing Fe-TiO₂ onto the functionalized activated carbon (AC). Nano-TiO₂ was synthesized using micromulsion method before modification with transition metal and deposited onto the oxidized AC. Photodegradation reaction of 1-butyl-3-methylimidazolium chloride [bmim]Cl was investigated under simulated visible light irradiation. It was observed that the overall efficiency of the system was increased with the increasing amount of Fe dopant. Investigation on the extrinsic factors such as solution pH, initial concentration of ILs and photocatalyst dosage showed to significantly affect the overall efficiency of the systems where the optimum condition for the system was observed at pH 10, with initial ILs at 1mM at 1 g/L of photocatalyst. The best performance photocatalyst was 0.2Fe-TiO₂/AC.

A new type of gold nanoparticles was synthesized by using benzoyl pyrazolone as a capping agent. The synthesized AuNPs exhibited a spherical shape and a monodisperse and fluorescence emission characteristic peak at 650 nm. The AuNPs –BMPBP was demonstrated as sensitive and selective fluorescent chemosensor for detection of Al ³⁺ ion. In the presence of Al ³⁺ ion, the fluorescent emission of BMPBP-AuNPs at 650 nm, increased with an increasing concentration of Al ³⁺ ion with a low detection limit (2 µM), the proposed method provided to apply determination of Al ³⁺ ion of tap water with satisfactory results.

Background: Although a cholesterol-lowering diet and the addition of plant sterols and stanols are suggested for the lipid management of children and adults with familial hypercholesterolemia, there is limited evidence evaluating such interventions in this population. Objectives: To investigate the impact of cholesterol-lowering diet and other dietary interventions on the incidence or mortality of cardiovascular disease and lipid profile of patients with familial hypercholesterolemia. Search methods: Relevant trials were identified by searching US National Library of Medicine National Institutes of Health Metabolism Trials Register and clinicaltrials.gov.gr using the following terms: diet, dietary, plant sterols, stanols, omega-3 fatty acids, fiber and familial hypercholesterolemia. Selection criteria: Randomized controlled trials evaluating the effect of cholesterol-lowering diet or other dietary interventions in children and adults with familial hypercholesterolemia were included. Data collection and analysis: Two authors independently assessed the trial eligibility and bias risk and one extracted the data, with independent verification of data extraction by a colleague. Results: A total of 17 trials were finally included, with a total of 376 participants across 8 comparison groups. The included trials had either a low or unclear bias risk for most of the parameters used for risk assessment. Cardiovascular incidence or mortality were not evaluated in any of the included trials. Among the planned comparisons regarding patients’ lipidemic profile, a significant difference was noticed for the following comparisons and outcomes: omega-3 fatty acids reduced triglycerides (mean difference [MD]: -0.27 mmol/L, 95% confidence interval [CI]: -0.47 to -0.07, p<0.01) when compared with placebo. A non-significant trend towards a reduction in subjects’ total cholesterol (MD: -0.34, 95% CI: -0.68 to 0, mmol/L, p=0.05) and low-density lipoprotein cholesterol (MD: -0.31, 95% CI: -0.61 to 0, mmol/L, p=0.05) was noticed. In comparison with cholesterol-lowering diet, the additional consumption of plant stanols decreased total cholesterol (MD: -0.62 mmol/l, 95% CI: -1.13 to -0.11, p=0.02) and low-density lipoprotein cholesterol (MD: -0.58 mmol/l, 95% CI: -1.08 to -0.09, p=0.02). The same was by plant sterols (MD: -0.46 mmol/l, 95% CI: -0.76 to -0.17, p<0.01 for cholesterol, and MD: -0.45 mmol/l, 95% CI: -0.74 to -0.16, p<0.01 for low-density lipoprotein cholesterol). No heterogeneity was noticed among the studies included in these analyses. Conclusions: Available trials confirm that the addition of plant sterols or stanols has a cholesterol-lowering effect on such individuals. On the other hand, supplementation with omega-3 fatty acids effectively reduces triglycerides and might have a role in lowering the cholesterol of patients with familial hypercholesterolemia. Additional studies are needed to investigate the effectiveness of a cholesterol-lowering diet or the addition of soya protein and dietary fibers to a cholesterol-lowering diet in familial hypercholesterolemia.

Neutrophil extracellular trap formation has been identified as a new cell death mediator, termed NETosis, which is distinct from apoptosis and necrosis. NETs capture foreign substances, such as bacteria, by releasing DNA into the extracellular environment, and have been associated with inflammatory diseases and altered immune responses. Short-chain fatty acids, such as acetate, are produced by the gut microbiota and reportedly enhance innate immune responses; however, the underlying molecular mechanisms remain unclear. Here, we investigated the effects of sodium acetate, which has the highest SCFA concentration in the blood and gastrointestinal tract, on NETosis by focusing on the mechanisms associated with histone acetylation in neutrophil-like HL-60 cells. Sodium acetate enhanced NETosis as shown by fluorescence staining with SYTOX green, and the effect was directly proportional to the treatment duration (16–24 h). Moreover, the addition of sodium acetate significantly enhanced the acetylation of Ace-H3, H3K9ace, H3K14ace, and H3K27ace. Sodium acetate-induced histone acetylation rapidly decreased upon stimulation with the calcium ionophore A23187, whereas histone citrullination markedly increased. These results demonstrate that sodium acetate induces NETosis via histone acetylation in neutrophil-like HL-60 cells, providing new insights into the therapeutic effects based on the innate immunity-enhancing effect of dietary fiber.

Collatz conjecture states that an integer $n$ reduces to $1$ when certain simple operations are applied to it. Mathematically, the Collatz function is written as $f^k(n) = \frac{3^kn + C}{2^{z}}$, where $z, k, C \geq 1$. Suppose the integer $n$ violates Collatz conjecture by reappearing as $2^in$, where $i \geq 1$, then the equation modifies to $n \left(1 - \frac{3^k}{2^{z}2^i}\right) = \frac{C}{2^{z}2^i}$. The article takes an elementary approach to this problem by calculating the bounds on the values of $\frac{C}{2^{z}2^i}$ and $1 - \frac{3^k}{2^{z}2^i}$. Correspondingly, an upper limit on the integer $n$ is placed that can re-appear in the sequence. The integer $n$ lies in the $(-\infty, 5)$ range, and the limit on the number of odd steps is $k < 3$. Finally, it is shown that no integer chain exists that does not lead to 1.

Background: The effect of rice bran arabinoxylan compound (RBAC), a plant-based immunomodulator, on the quality of life (QoL) in cancer patients and underlying physiological pathways remains unclear. Trial design: The RBAC-QoL study is a double-blind, randomised, controlled pilot feasibility study. The aim is to determine RBAC’s effects on QoL and the associated action mechanisms. Primary outcomes are the EORTC QLQ-C30 functional, symptom, and global QoL scores with inflammatory, nutritional, and cytokine parameters as secondary and exploratory outcomes. Methods: Recruitment targets adults diagnosed with solid organ tumours (≥ stage II) undergoing active treatment in several outpatient centres in New South Wales, Australia. Interventions are RBAC or matched placebo at 3g/day for 24 weeks allocated through stratified randomisation with participants, oncologists, and data collectors blinded. Data is collected from five study visits six weeks apart. The trial is ongoing. An interim intention-to-treat analysis was performed using repeated measure ANOVA with pairwise comparisons where statistical significance is observed and adjusted with covariates. Results: Global QoL scores from currently available data (n = 16; RBAC = 7, placebo = 9) were statistically different between groups (F[1,8] = 8.6, p = 0.019, eta2[g] = 0.267). Pairwise comparisons found significant differences at week 6 (p = 0.032, Cohen’s d = 1.454) and marginally at week 12 (p = 0.069, d = 1.427). Age-adjusted analysis showed a continuous upward trend in QoL improvement over time with RBAC, while the placebo group did not deviate from baseline QoL. Significant elevations of serum white blood cell count (week 18) and total protein (weeks 12 and 18) were detected in the RBAC group compared to placebo. The total protein levels correlated highly with white blood cell count (Pearson’s r = 0.539, p < 0.001) and moderately with the global QoL scores (r = 0.338, p = 0.01). No intervention-related adverse events were reported in both groups. Conclusions: RBAC improves QoL beyond placebo during active cancer treatment, possibly through the immuno-nutritional pathway. These findings are preliminary but valuable for future research. Funding and registration: Daiwa Pharmaceutical Co., Ltd, Japan; BioMedica Nutraceuticals Pty Ltd., Australia. ANZCTR Reg No: ACTRN12619000562178p.

Abstract Introduction: Visual perceptual skills are essential for independent participation in self-care tasks, educational, work and leisure time activities. The effect of HIV on the visual perceptual skills is not well understood among children in low resource settings like Zimbabwe. Methods: A cross sectional comparative study was done with 30 children living with HIV and 30 children living without HIV residing in Harare urban area. The TVPS-3 was used to assess their visual perceptual skills. SPSS version 22, STATISTICA 13 and Microsoft 2016 were used for data analysis. Results: Both groups of children had mean percentile ranks below 50 on their TVPS-3 scores. Children without HIV generally performed better than those with HIV but the difference was not statistically significant in most cases. Through univariate analysis, only performance on Spatial Relations significantly differed between the two groups. Both groups had lowest scores in Basic visual perceptual skills. Age and school grade were the independent predictors of the children’s performances in the study. Conclusion: There is need for Occupational therapy services in public primary schools and in the pediatric Opportunistic Infections clinics in hospitals to be part of the health team which caters for children with visual perceptual challenges.

The taxonomy of trilobites Abadiella Hupé, 1953 and Parabadiella Zhang, 1966 from the lower Cambrian of Gondwana has long been a controversy. Based on newly-collected and formerly-reported materials, 94 trilobite cranidia within 21 species are selected for morphometric analyses: principal components analysis (PCA) and canonical variates analysis (CVA). The integrated morphological characters are successfully accounted for by two principal components in PCA. The further validations for the presupposed qualitative groupings are indispensable to detect and calibrate the ultimate taxonomic results in CVA. By this way, all specimens distributed in a consistent morphospace in PCA and the short distances between them demonstrate their close morphological affinity, supporting their congeneric status within Abadiella. Additionally, three morphotypes were recognized from all selected specimens and they were eventually revised and incorporated into A. bourgini Hupé, 1953, A. huoi Zhang, 1966, and A. yunnanensis Luo, 1981, through stepwise test-calibration to get a high correct rate as far as possible in CVA. From this, it is certain that A. huoi is conspecific in South Australia and South China. Its occurrence allows to correlate the Australian A. huoi Range Zone to the identical zone in South China (in platform), having an approximately consistent stratigraphic range in the two regions. In comparison with A. huoi, A. bourgini was reported from fewer localities in South China. Nevertheless, its presence in the Daguinaspis Zone of Issendalenian Stage in Morocco permits a correlation with Chinese and Australian A. huoi Zone. As an auxiliary marker for A. huoi, the occurrence of A. bourgini in Morocco, South Australia and South China reinforce the correlation potential and resolution in species-level for the Cambrian Stage 3 in Gondwana region.

In the last decades droughts, deforestation and wildfires have become recurring phenomena that have affected both human activities and natural ecosystems in Amazonia. The time an ecosystem requires to recover from carbon losses is a crucial metric to evaluate disturbance impacts on forests. However, the factors influencing and controlling the recovery time and its spatiotemporal patterns at the regional scale are still poorly understood. In this study, we combined forest growth model, remote sensing and field plots, to map Amazonia-wide (300-ha resolution) impact and recovery time of aboveground biomass (AGB) after drought, fire and a combination of logging and fire. Our simulated results indicate that AGB decreases by 4%, 19% and 46% in forests disturbed by drought, fire and logging + fire, respectively, with an average AGB recovery time of 27 years for drought, 44 years for burned and 63 years for logged + burned areas and with maximum values reaching 184 years in areas of high fire intensity. Our findings provide two major insights in the spatial and temporal patterns of drought and wildfire in the Amazon: 1) the recovery time of the forests takes longer in the southeastern part of the basin, and, 2) as droughts and wildfires become more frequent – since the intervals between the disturbances is getting shorter than forest regeneration – potentially causing a long-lasting damage in these fragile ecosystems and a permanent degradation.

Novel effluent treatment solutions for dangerous organic pollutants are crucial worldwide. In recent years, chemical reduction using noble metal-based nanocatalysts and NaBH4, a reducing agent, has become common practice for eliminating organic contaminants from aquatic environments. We suggest a straightforward approach to synthesizing magnetic cellulose nanocrystals (CNC) modified with magnetite (Fe3O4) and silver nanoparticles (Ag NPs) as a catalyst for organic contamination removal. Especially, Ag NPs were decorated on the CNC surface without reducing agents or stabilizers by reducing AgNO3. XRD, FE-SEM, TEM, EDX, VSM, BET, and zeta potential tests characterized the Ag/Fe3O4/CNC nanocomposite. The nanocomposite's catalytic activity was tested by eliminating 4-nitrophenol (4-NP) and organic dyes methylene blue (MB) and methyl orange (MO) in an aqueous solution at 25 oC. The Ag/Fe3O4/CNC nanocomposite reduced 4-NP and decolored these hazardous organic dyes in short time (2 to 5 min) using a tiny amount of catalyst (2.5 mg for 4-NP and 15 mg for MO and MB). The magnetic catalyst was removed and reused three times without losing catalytic activity. This work shows that the Ag/Fe3O4/CNC nanocomposite can chemically reduce harmful pollutants in effluent for environmental applications.

Malignant gliomas are heterogeneous neoplasms. Glioma stem-like cells (GSCs) are undifferentiated and self-renewing cells that develop and maintain these tumors. These cells are the main population that resist current therapies. Genomic and epigenomic analyses has identified various molecular subtypes. Bone morphogenetic protein 4 (BMP4) reduces the number of GSCs through differentiation and induction of apoptosis, thus increasing therapeutic sensitivity. However, the short half-life of BMP4 impedes its clinical application. We have previously reviewed BMP4 signaling in central nervous system development and glioma tumorigenesis and its’ potential as a treatment target in human gliomas. Recent advances in understanding both adult and pediatric malignant gliomas highlight critical roles of BMP4 signaling pathways in the regulation of tumor biology, and indicate its’ potential as a therapeutic molecule. Furthermore, significant progress has been made on synthesizing BMP4 biocompatible delivery materials, which can bind to and markedly extend BMP4 half-life. Here, we review current research associated with BMP4 in brain tumors, especially in pediatric malignant gliomas. We also summarize BMP4 delivery strategies, with a focus on biocompatible BMP4 binding peptide amphiphile nanostructures as promising novel delivery platforms for treatment of these devastating tumors.

We previously reported that corneal fibroblasts within 3D fibrin matrices secrete, bind, and organize fibronectin into tracks that facilitate cell spreading and migration. Other cells use these fibronectin tracks as conduits, which leads to the development of an interconnected cell/fibronectin network. In this study, we investigate how cell induced reorganization of fibrin correlates with fibronectin track formation in response to two growth factors present during wound healing: PDGF BB, which stimulates cell spreading and migration; and TGFβ1, which stimulates cellular contraction and myofibroblast transformation. Both PDGF BB and TGF stimulated global fibrin matrix contraction (P < 0.005), however cell and matrix patterning were different. We found that during PDGF BB induced cell spreading, fibronectin was organized simultaneously with the generation of tractional forces at the leading edge of pseudopodia. Over time this led to the formation of an interconnected network consisting of cells, fibronectin and compacted fibrin tracks. Following culture in TGFβ1, cells were less motile, produced significant local fibrin reorganization, and formed fewer cellular connections as compared to PDGF BB (P < 0.005). Although bands of compacted fibrin tracks developed in between neighboring cells, fibronectin labeling was not generally present along these tracks, and the correlation between fibrin and fibronectin labeling was significantly less than that observed in PDGF BB (P < 0.001). Taken together, our results show that cell-induced ECM reorganization can occur independently from fibronectin patterning. Nonetheless, both events seem to be coordinated, as corneal fibroblasts in PDGF BB secrete and organize fibronectin as they preferentially spread along compacted fibrin tracks between cells, producing an interconnected network in which cells, fibronectin and compacted fibrin tracks are highly correlated. This mechanism of patterning could contribute to the formation of organized cellular networks that have been observed following corneal injury and refractive surgery.

Background: Over the past years, there has been a rise in the incidence of type 1 diabetes, partic-ularly among younger individuals. This concerning trend has prompted investigations into po-tential contributing factors, with intestinal dysbiosis emerging as a likely culprit for the escalating annual rates of the disease; (2) Methods: We conducted a retrospective ecologic correlational study involving 37 children from the southern region of Romania between 2019-2021. All participants were within the first six months following the onset of the disease; (3) Results: In the microbiota of the patients we observed a dysbiosis marked by an overabundance of bacteria (Clostridium coccoides, Faecalibacterium, Bacterioides, Enterobacteriaceae) and fungi, compared to the healthy control group. The Spearman correlation revealed a positive association between the presence of Bacteroides (p=0.0442), Butyricicoccus (p=0.0164), and Clostridium leptum (p=0.0023) with recent diabetes onset. Furthermore, a significant correlation was observed between younger age at onset and the pres-ence of Butyricicoccus (p=0.019). The use of antibiotics in the month preceding admission was linked to the presence of fungi in the microbiota (Candida, p=0.0442); (4) Conclusions: The dysbiosis of Romanian type 1 diabetes children correlates with inflammation, more severe onset of the disease and other au-toimmune diseases.

Before the adaptive immune response is established, retroviruses can be targeted by several cellular host factors at different stages of the viral replication cycle. This intrinsic immunity relies on a large diversity of antiviral processes. In the case of HTLV-1 infection, these active innate host defence mechanisms are debated. Among these mechanisms, we focused on a RNA decay pathway called nonsense-mediated mRNA decay (NMD), which can target multiple viral RNAs, including HTLV-1 unspliced RNA, as it has been recently demonstrated. NMD is a cotranslational process that depends on the RNA helicase UPF1 and regulates the expression of multiple types of host mRNAs. RNA sensitivity to NMD depends on mRNA organization and the ribonucleoprotein (mRNP) composition. HTLV-1 has evolved several means to evade the NMD threat, leading to NMD inhibition. In the early steps of infection, NMD inhibition favours the production of HTLV-1 infectious particles, which may contribute to the survival of the most fit clones despite genome instability; however, its direct long-term impact remains to be investigated.

The steady-state dissolution rates of basaltic glass and labradorite have been measured in the presence of 10 to 700 x 10-3 mol kgw-1 aqueous NaCl, KCl, CaCl2, and MgCl2 at 25 oC. All rates were measured in mixed flow reactors, and at pH~3.6 by the addition of HCl to the reactive fluids. Steady-state basaltic glass dissolution rates based on Si release increased by ~0.3 log units in the presence of 1 x 10-2 mol kgw-1 of CaCl2 or MgCl2, compared to their rates in 10 x 10-3 mol kgw-1 of NaCl, and KCl. In contrast, the steady-state dissolution rates of labradorite decreased by ~0.4 log units in the presence of 10 x 10-3mol kgw-1 of CaCl2 or MgCl2, compared to their rates in 10 x 10-3 mol kgw-1 of NaCl, and KCl. These contrasting behaviours likely reflect the varying effects of these cations on the stability of rate controlling Si-rich activated complexes on the surface of the solids. On average, the Si release rates of these solids are similar to each other and increase slightly with increasing ionic strength. As the pH of water charged with 10 to 30 bars CO2 is ~3.6, the results of this study indicate that both basaltic glass and labradorite dissolution will likely be effective at increasing pH and adding Ca to the aqueous phase in saline fluids. This observation supports potential efforts to store carbon through its mineralization in saline aquifers containing Ca-bearing feldspar and in submarine basalts.

Cellulose nanocrystals (CNCs) are a kind of nano-inclusions that have experienced tremendous expansion in the material industry due to their outstanding mechanical qualities, sizable surface area, and capacity for functional tuning. Due to their vast potential, however, present practises fall short of fully using them. For example, employing CNCs in various matrices with various surface chemistries can be challenging; this problem tends to get worse if the focus is furthered on bio-based applications. This paper reviews the use of CNCs as fillers in natural and man-made polymers; we have explored in depth the production, characterisation, and of CNCs from various sources and their inclusion into various matrices. Surface alterations and the introduction of CNCs in biodegradable polymer can have a significant impact on several industrial behemoths such as tissue engineering and biomedical applications; therefore, pursue of current manuscript is extremely warranted. Throughout the manuscript various assembly techniques that involves alteration and adjustment of polymer network in building up a hydrogel with higher fracture energy and mechanical properties are also included. From rheological perspective the hydrogel processing is also discussed with some models routinely used in the literature to describe these hydrogels. Finally, bio-based hydrogels mechanically reinforced with CNCs such as Xanthan Gum, Alginate, protein, and polysaccharides were discussed.

Background: Monoclonal antibodies against PD-1 or PD-L1 are established in clinical practice for the treatment of both early and advanced/metastatic triple-negative breast cancer. Beyond the established immune checkpoints (ICPs) (PD-1 and CTLA-4) additional ICPs such as lymphocyte activation gene-3 (LAG-3) are subject of current research. In the present retrospective gene ex-pression analysis, we evaluated the prognostic significance of LAG-3 in 461 patients with early breast cancer. In addition, we examined whether there was a correlation between the different ICPs and CD8 expression. Methods: Using microarray-based gene expression analysis, we examined the prognostic signif-icance for metastasis-free survival (MFS) of LAG-3 mRNA expression in the whole cohort of 461 breast cancer patients and among different molecular subtypes. Correlations were analyzed us-ing Spearman-Rho correlation coefficient. Results: In the whole cohort, LAG-3 expression had no significant impact on MFS (p = 0.712, Log Rank). In the subgroup analyses, there was a trend, that higher LAG-3 expression was associated with favorable outcome in the luminal B (p = 0.217), basal-like (p = 0.370) and HER2 (p = 0.089) subtypes, although significance was not reached. In contrast, in multivariate Cox regression analysis adjusted for age, tumor size, axillary nodal status, histological grade of differentiation and the proliferation marker Ki-67, LAG-3 showed a significant influence on MFS (HR 0.574; 95% CI 0.369–0.894; p = 0.014). High LAG-3 significantly correlated with CD8 ( = 0.571; p < 0.001). Conclusion: LAG-3 expression had an independent impact on MFS. In addition to PD-1 and PD-L1, further immune checkpoints such as LAG-3 could serve as therapeutic targets in breast cancer.