Among the many Lysosomal Storage Disorders (LSDs) that would benefit from the establish-ment of novel cell models, either patient-derived or genetically engineered, is Mucopolysaccha-ridosis type II (MPS II). In fact, even though a specific therapeutic approach does exist for this disorder (Enzyme Replacement Therapy, ERT, with recombinant human IDS) and haematopoiet-ic stem cell transplantation (HSCT) may also hold promise whenever the disorder is diagnosed soon enough, both approaches have their own drawbacks. Here we present our results on the establishment and characterization of two MPS II pa-tient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population is isolated from LSD patient samples obtained from the oral cavity. Taking into account our results on the molecular and biochemical characterization of those cells and our first insights on their subcellular MPS phenotype, we consider these cells will be a valuable tool for both pathophysiological assessments and drugs screenings. Ultimately, we believe patient-derived dental pulp stem cells (DPSC) may represent a feasible alternative to induced pluripotent stem cells (iPSC) in many labs with standard cell culture con-ditions and limited (human and economic) resources.

In this research paper, we address the critical role of data security in the rapidly evolving FinTech sector. We explore the challenges and strategies for establishing robust data security systems, emphasizing the consequences of data breaches and common vulnerabilities. The paper highlights the efficacy of technologies like encryption, blockchain, and cloud security, supported by real-world case studies from leading FinTech companies. Additionally, we examine regulatory frameworks and standards essential for maintaining data security. Concluding with the proposal of an integrated security system model, the paper underscores the synergy between technological innovation, regulatory compliance, and proactive risk management in the FinTech industry

Microencapsulation of polyherbal formulation (PHF) extract was carried out by freeze drying method, by employing gum arabic (GA), gelatin (GE), and maltodextrin (MD) with their designated different combinations as encapsulating wall materials. Antioxidant components (i.e total phenolic contents (TPC),Total flavonoids contents (TFC), and total condensed contents (TCT)), antioxidant activity (i.e. DPPH, β-carotene & ABTS⁺ assays), moisture contents, water activity (aw), solubility, hygroscopicity, glass transition temperature (T_g), particle size, morphology, in vitro alpha-amylase and alpha-glucosidase inhibition and bioavailability ratios of the powders were investigated. Amongst all encapsulated products, T_B (5% GA and 5% MD) and T_C (10% GA) has proven to be the best treatments with respect to the highest preservation of antioxidant components and their antioxidant potential by DPPH and β-carotene assays and noteworthy for an ABTS⁺ assays, in addition, the aforesaid treatments also demonstrated lower moisture content, aw, particle size and higher solubility, hygroscopicity and glass transition temperature (T_g). All freeze dried samples showed irregular (asymmetrical) microcrystalline structures. Furthermore, T_B and T_C also illustrated the highest in vitro anti-diabetic potential due to great potency for inhibiting alpha-amylase and alpha-glucosidase activities. In the perspective of bioavailability, T_A, T_B and T_C demonstrated the excellent bioavailability ratios (%).Futhermore, the phytochemo-profiling of ethanolic extract of PHF was also revealed to find out the bioactive compounds.

This paper discussed the concept of quality assurance (QA) in higher education and its implications to higher education institutions (HEIs) and the possible challenges. The study evaluated literature concerning QA in Zambia and elsewhere. The findings of the study show that QA is implemented through external and internal mechanisms such as accreditation, registration, institutional auditing, and the use of external examiners, self-evaluation, and peer reviews. The QA implications to HEIs in Zambia are that there is a need for accreditation of academic programmes with the Higher Education Authority (HEA) by HEIs. Further, HEIs should establish QA units to spearhead quality issues, reactive, and introduce the use of external examiners to ensure quality. The challenges identified in the implementation of QA in HEIs include inadequate funding, infrastructure, shortage of qualified academic staff, and lack of standalone QA units in some HEIs. In this regard, it has been recommended among other things, government improve funding in public HEIs, construct infrastructure, HEIs establish QA units, and recruit and retain qualified academic staff to ensure the quality of education.

Al has very good corrosion resistance and corrosion properties. The corrosion resistance of Al cast alloys is different because these alloys contain a lot of elements. Especially in secondary alloys which contain more impurity elements from which Fe is the most common. This study deals with secondary AlSi7Mg0.3 cast alloys which contain more Fe and are affected by a chloride corrosion environment. This environment was selected based on the application of castings in the automo-tive industry. The main object was to research the effect of such an environment on basic me-chanical properties and fatigue properties. The results show that a higher Fe content does not lead to a significant reduction in the properties of the casting and the chloride environment is not so harmful. Therefore, can be stated that the investigated secondary sand-cast experimental materials can replace the primary alloys without losing the required corrosion and mechanical properties.

Background: Redo mitral valve surgery is the standard of care for failed mitral bioprostheses or recurrence of mitral regurgitation after repair. Nonetheless, catheterbased valve-in-valve (ViV) or valve-in-ring (ViR)-procedures increasingly become viable alternatives in high risk subpopula-tions. Despite reported good initial results, only little is known about longer-term outcomes. The present series report long-term outcomes of transcatheter mitral ViV- and ViR-procedures. Methods: All consecutive patients (n=54) undergoing transcatheter mitral ViV- or ViR-procedures for failed bioprostheses or recurring regurgitation after mitral repair were retrospectively en-rolled in the time period between 2011 and 2021. The mean age was 76.5 ± 6.5 years, and 30 (55.6%) of the patients were male. The procedures were done using a commercially available balloon-expandable transcatheter heart valve. Clinical and echocardiographic follow-up data were obtained out of the hospital’s database and analyzed. Follow-up reached up to 9.9 years with a total of 164.3 patient-years. Results: A total 25 patients received a ViV- and 29 patients a ViR-procedure. Both groups were at high surgical risk with an STS-PROM of 5.9 ± 3.7 % in ViV- and 8.7 ± 9.0% in ViR-patients, respectively (p<0.01). The procedures itself were mainly unevent-ful with no intraoperative deaths and a low conversion rate (n=2/54; 3.7%). VARC-2 procedural success was low (ViV 20.0% and ViR 10.3%; p=0.45), which was either driven by high rates of transvalvular pressure gradients “>5mmHg” (ViV 92.0% and ViR 27.6%; p<0.01) or residual regurgitation “>trace” (ViV 28.0% and ViR 82.7%; p<0.01). ICU-stay was prolonged in both groups (ViV 3.8 ± 6.8 days and ViR 4.3 ± 6.3 days; p=0.96) with acceptable hospital stay (ViV 9.9 ± 5.9 days and ViR 13.5 ± 8.0 days; p=0.13). Despite 30-days mortality was acceptable (ViV 4.0% and ViR 6.9%; p=1.00), the mean posthospital survival time was disappointingly low (ViV 3.9 ± 2.6 years and ViR 2.3 ± 2.7 years; p<0.01). Overall survival I the entire group was 33.3%.Cardiac reasons for death were frequent in both groups (ViV 38.5% and ViR 52.2%). Cox-regression analysis identified ViR-procedures as a predictor of mortality (HR 2.36, CI 1.19 - 4.67, p=0.01). Conclusions: Despite acceptable immediate outcomes in this high-risk subpopulation, long-terms results are discouraging. Transvalvular pressure gradients as well as residual regurgitations remained drawbacks in this real-world population. The indication for catheterbased mitral ViV- or ViR-procedures thoughtfully must be made in consideration of conventional redo-surgery or conservative treatment.

This study empirically analyzes the effectiveness of resource optimization utilizing artificial intelligence (AI) within cloud computing environments. It compares systems that have been transitioned from a Monolithic structure to Microservices Architecture (MSA) with those adopting a simple Rehost strategy, to validate the operational efficiency of two systems whose resource efficiency has been enhanced compared to traditional legacy systems. The research is based on systems that determined resource efficiency post-cloud migration using APM tools. It points out the limitations of traditional heuristic operation methods in resource optimization, which lead to issues such as application performance degradation, resource over-allocation, and increased operational costs. This study aims to overcome the conventional resource optimization standards that depended on the average peak usage of CPU and memory infrastructure, by introducing AI-based optimization tools, and applying on-premise standards to cloud and container environments to achieve resource optimization. The paper emphasizes the importance of resource optimization through AI-based automation tools, exploring the possibilities of resolving real-world application performance issues in cloud environments, reducing unnecessary resource usage costs, and cutting down on labor risks and operational expenses. Through this, it presents strategic directions on how AI technology can offer financial and operational advantages in managing cloud resources.

The United Nations Sustainable Development Goals call for the eradication of poverty, and China has proposed the Rural Revitalization Strategy based on the achievements of its poverty alleviation efforts in 2020. As a vital component of this strategy, the impact of land transfer on farmers' income growth has become a hot topic in both theoretical and practical sectors. This paper utilizes data from the CFPS database for the years 2010-2018 to construct OLS regression models and a Heckman two-stage model to analyze the effects of land transfers on the incomes of different types and sources among farmers. The empirical results show: First, land transfers do promote income growth among farmers, but the effect is primarily positive for those transferring out land, with negligible impact on those acquiring land. Second, the impact of land transfers varies between different types of income for transferees and transferors. Wage income contributes up to 88.26% to the income growth of transferors, a significantly higher rate than the decrease in business income; however, the increase in business income for transferees does not offset the decline in wage income, leading to no significant change in overall income. Further sensitivity analysis using the Heckman two-stage model confirms the robustness of these findings. The conclusions of this study provide theoretical and empirical evidence to optimize land transfer policies, enhance participation in land transfers, and ultimately achieve the mission of rural revitalization.

The effect of the melt cooling rate on the atomic ordering of austenite and, as a consequence, on the martensitic transformation of a nonstoichiometric alloy of the Ni-Mn-In system has been studied. In-situ TEM observations revealed differences in the mechanism of phase transformations of the alloy subjected to different cooling conditions. It is shown that during quenching a high density of antiphase boundaries (APB) is formed and the alloy is in the austenite-martensitic (10M and 14M) state up to a temperature of 120K. In a slowly cooled alloy, a lower APB density is observed, and a two-stage transformation L21/B2 → 10M → 14M occurs in the range of 150–120 K.

Ovariectomy appears to be the best method to control the density of wild ungulate populations. The aim of the present study was to compare two surgical approaches, via the flank and midline, in mouflon’s ovariectomy in field conditions. Twenty female mouflons were enrolled in the study. The animals were divided randomly in two groups, Group F animals were gonadectomized via flank approach, while Group A animals were sterilized via linea alba access. The parameters evaluated were duration of surgery, duration of anaesthesia, recovery time, intra- and post-operative complications, intra-operative nociception and pain in the post-operative period. There were no intra- and post-operative complications. The evaluated parameters showed a very similar trend in both groups. Both techniques are found to be effective and safe in execution.

The use of nanomaterials has been increasing in recent times, and they are widely used in industries such as cosmetics, drug, food, water treatment and agriculture. The rapid development of new nanomaterials demands a set of approaches to evaluate the potential toxicity and risks related to them. In this regard, nanosafety has been using and adapting already existing methods (toxicological approach), but the unique characteristics of nanomaterials demand new approaches (nanotoxicology) to fully understand the potential toxicity, immunotoxicity and (epi)genotoxicity. Also, new technologies, such as organ-on-chip and sophisticated sensors, are under development and/or adaptation. All the information generated is used to develop new in silico approaches trying to predict the potential effects of newly developed materials. The overall evaluation of how from the production to final disposition chain of nanomaterials is evaluated under Life Cycle Assessment (LCA), which is becoming an important element of nanosafety considering sustainability and environmental impact. In this review we give an overview of all these elements of nanosafety.

Recently, the indications for Cochlear Implant (CI) have also been extended to subjects with Single Sided Deafness (SSD) in order to restore binaural hearing. The primary objective of this study was to investigate the advantages of CI following one year of usage in SSD subjects. Secondarily we want to assess the long-term stability of the CI. 57 participants performed a complete audiological assessment (speech audiometry in quiet and in noise and localization test). For each was also evaluated subjective hearing profile (with Speech Spatial and Qualities_SSQ questionnaire) and the impact of tinnitus (with the use of Tinnitus Handicap Inventory_THI questionnaire) After one year of CI usage, we observed a significant improvement in speech-to-noise ratio, in sound localization abilities, in the Speech (p-value 0.001) and Spatial (p-value 0.001) subscales of the SSQ questionnaire and in THI questionnaire (p-value 0.001). The improvements in speech in noise and localization abilities and the reduction of the SSQ and THI questionnaires scores were maintained over time (6th to 60th month follow-up). Only eight participants did not fully utilize the CI. CI in SSD represents an effective method for improving speech recognition in noisy environments, restoring sound localization abilities, reducing tinnitus and improve subjective listening skills.

Endometriosis is a common finding among women with infertility and women who are diag-nosed with endometriosis are almost twice as likely to experience infertility. Mechanisms by which endometriosis causes infertility remain poorly understood. In this review we evaluate the current literature on the impact of endometriosis on oocyte and embryo quality. The presence of endometriosis evidently reduces ovarian reserve, oocyte quality and embryo quality, however this does not appear to translate to a clear clinical impact. Analysis of data from large assisted reproduction technology registries has shown that women with endometriosis have a lower oo-cyte yield but no reduction in reproductive outcomes. There is a need for future studies in the form of well-designed randomised controlled trials to further evaluate the role of surgical and medi-cal treatment options in women with endometriosis undergoing assisted conception.

The non-structural protein (NS) and nucleoprotein (NP) of the severe fever with thrombocytopenia syndrome virus (SFTSV) encoded by the S segment are crucial for viral pathogenesis. They reside in viroplasm-like structures (VLS), but their interaction and their significance in viral propagation remain unclear. Here, we investigated the significance of the association between NS and NP during viral infection through in-silico and in-vitro analyses. Through in-silico analysis, three possible binding sites were predicted, at NSs1-32, NSs56-82, and NSs207-237. Rationally, three mutant NSs were developed by site-directed mutagenesis and tested for NP interaction by co-immunoprecipitation. NSsW61Y failed to interact with the nucleoprotein, which was substantiated by the conformational changes observed in the structural analyses. Additionally, molecular docking analysis corroborated that the NSW61Y mutant protein does not interact well compared to wild-type NS. Over-expression of wild-type NS in HeLa cells increased the SFTSV replication by five folds, but NSsW61Y exhibited 1.9-folds less viral replication than wild-type. We demonstrated that the W61Y alteration was implicated in the reduction of NS-NP interaction and viral replication. Thus, the present study identified a critical NS site, which could be targeted for development of therapeutic regimens against SFTSV.

To mitigate the COVID-19 infection, many world governments endorsed the cessation of non-essential activities, such as the school attendance. Thereby, forcing the evolution of the teaching model to the virtual classroom. In the present work we show the application of a modified version of the adapted COVID-19 stress scales (ACSS) which also included teaching anxiety and preparedness, and resilience for academic professionals in Mexico, during the unprecedented transformation of the education system undergone in the COVID-19 quarantine. Most of the studied variables: gender, age, academic degree, household occupants, having a disease, teaching level, teaching mode, work hours, resilience, teaching anxiety and preparedness, and fear of being an asymptomatic patient (FOBAP), showed significant statistical correlation between each other (p<0.050) and to the 6 areas of the ACSS (danger, contamination, social economical, xenophobia, traumatic stress and compulsive checking). Our results further showed that the perceived stress and anxiety, fell into the category of absent to mild with only the danger section of the ACSS falling into the moderate category. Finally, resilience generated throughout the quarantine, seems to be a predictor of the adaptation the academic professional has undergone to cope with stress.

Among the alternatives pointed out as able to make livestock a more efficient activity and reduce its environmental impact, the use of feeds with high digestibility and the use of non-conventional fodder species can be highlighted. Tithonia diversifolia (Hemsl.) A. Gray (TD) has already gained attention as a feed for ruminants. Nonetheless, there has been little discussion about the impacts of this plant on the rumen dynamics that lead to better animal performance. The aim of this study was to assess how increasing levels of TD could affect ruminal microbial biomass synthesis, degradability, and in vitro gas production (IVGP) of diets. Four diets were evaluated: a control diet (TD0: 400 g kg-1 soybean meal and corn grain, and 600 g kg-1 Tifton 85 hay (Cynodon spp)) and three increasing levels of TD (TD9: 90, TD27: 270, and TD45: 450 g kg-1 – dry matter basis) as a replacement for dietary roughage. A 96-hour IVGP assay was carried out and five incubation times (2, 4, 10, 24, and 96 hours) were used for degradability determination. Gas produced, methane (CH4), degradability of organic matter (IVDOM), short-chained fatty acid (SCFA) production, partitioning factor (PF), and microbial biomass (MB) were evaluated among treatments. There was no significant effect (P&gt;0.05) between TD inclusion and IVGP at most incubation times; only at 6 hours of incubation did gas production increase linearly with TD inclusion (R2=0.19; P&lt;0.05). TD inclusion had no effects on CH4. IVDOM increased linearly with TD inclusion at 6 and 10 hours, with TD45 being more degradable than the control diet at 6 hours only. There was a positive linear relationship (R2=0.20; P&lt;0.05) between TD inclusion and PF. TD45 had significantly higher PF values than the control. MB also increased linearly (R2=0.30; P&lt;0.05) with TD inclusion, and all diets with TD had significantly more MB than the control diet. The inclusion of TD at the levels used in this work was revealed to have a positive impact on microbial protein synthesis, which could be related to the higher microbial efficiency of increased substrate quality.

The World Anti-Doping Agency has prohibited gene doping in the context of progress in gene therapy. There is a risk that the artificial regulation of genes using plasmids could be applied for gene doping. However, no gold standard method to detect this has been established. Here, we aimed to develop a method to detect multiple transgene fragments as proof of gene doping. First, gene delivery model mice as a mimic of gene doping were created by injecting firefly luciferase plasmid with polyethylenimine (PEI) into the abdominal cavity. The results confirmed successful establishment of the model, with sufficient luminescence upon in vivo imaging. Next, multiple transgene fragments in the model were detected in plasma cell-free (cf)DNA, blood-cell-fraction DNA, and stool DNA using the TaqMan-qPCR assay, with the highest levels in plasma cfDNA. Using just a single drop of whole blood from the model, we also attempted long-term detection. The results showed that multiple transgene fragments were detected until 11 days. These findings indicate that the combination of plasma cfDNA or just one drop of whole blood with TaqMan-qPCR assay is feasible to detect plasmid-PEI-based gene doping. Our findings could accelerate the development of methods for detecting gene doping in humans.

Based on the geochemical analysis of the volcanic material from the sediment core AMK-340, central zone of the Reykjanes Ridge, we could detect two ash-bearing sediment units accumulated during the Termination I. They correlate to the Ash Zone I in the North Atlantic Late Quaternary sediments having an age of 12170-12840, within the Younger Dryas cold chronozone, and 13600-14540 years, within and Bølling-Allerød warm chronozone. The ash of the Younger Dryas unit is presented mostly by the mafic and persilicic material originated from the Icelandic volcanoes; Vedde Ash is presented in one sediment sample from this unit. The ash of the Bølling-Allerød unit is presented mostly by the mafic shards which are related to the basalts of the rift zone on the Reykjanes Ridge, having presumably the local origin. A detection of Vedde Ash helped to specify the timing of the previously reconstructed paleoceanographic changes for the Termination I in the point of study: a significant warming in the area could occur as early as 300 years prior to the end of the conventional Younger Dryas cold chronozone.

In the study of relativistic jets one of the key open questions is their interaction with the environment on the microscopic level. Here, we study the initial evolution of both electron–proton (e^- - p⁺) and electron–positron (e^±) relativistic jets containing helical magnetic fields, focusing on their interaction with an ambient plasma. We have performed simulations of "global" jets containing helical magnetic fields in order to examine how helical magnetic fields affect kinetic instabilities such as the Weibel instability, the kinetic Kelvin-Helmholtz instability (kKHI) and the Mushroom instability (MI). In our initial simulation study these kinetic instabilities are suppressed and new types of instabilities can grow. In the e^- - p⁺ jet simulation recollimation-like instability occurs and jet electrons are strongly perturbed. In the e^± jet simulation a recollimation-like instability occurs at early times followed by a kinetic instability and the general structure is similar to a simulation without helical magnetic field. Simulations using much larger systems are required in order to thoroughly follow the evolution of global jets containing helical magnetic fields.

Here, we report on ZnO nanoparticles (NPs) generated by nanosecond pulsed laser (Nd:YAG, 1064 nm) through ablation of metallic Zn target in water and air and their comparative analysis as potential nanomaterials for biomedical applications. The prepared nanomaterials were carefully characterized in terms of their structure, composition, morphology and defects. It was found that in addition to the main wurtzite ZnO phase, which is conventionally prepared and reported by others, the sample laser-generated in air also contained some amount of monoclinic zinc hydroxynitrate. Both nanomaterials were then used to modify model wound dressings based on biodegradable poly-L-lactic acid. The as-prepared model dressings were tested as biomedical materials with bactericidal properties towards S. aureus and E. coli strains. The advantages of the NPs prepared in air over their counterparts generated in water found in this work are discussed.

In contemporary design practices, there is a disconnect between the design techniques used for early-stage design experimentation and performance analysis, and those used for the manufacture and construction. This study addresses the problems in developing an integrated digital design workflow and provides a research framework for integrating environmental performance requirements with robotic manufacturing processes on a construction site. The proposed method enables the user to import a design surface, identify design parameters, set several environmental performance goals, and thereafter simulate and select a robotic building strategy. Based on these inputs, design alternatives are developed and evaluated, considering their robotically simulated constructibility, in terms of their performance criteria. To validate the proposed method, the design is evaluated in an experiment wherein a double-skin facade perforation is generated using the proposed methodology. The results suggest a heuristic feature to improve the simulated robotic constructibility. Moreover, the functionality of the prototype is demonstrated.

In this review article, the occurrence of nor-lignans and their biological activities are explored and described. Nor-lignans have proven to be present in several different families also belonging to chemosystematically distant orders as well as to have many different beneficial pharmacological activities. This review article represents the first one on this argument and is thought to give a first overview on these compounds with the hope that their study may continue if not raise after this.

Paratuberculosis (PTB) is a chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP) that affects a wide variety of domestic and wild animals. It is considered as one of the diseases with the highest economic impact in the ruminant industry. Despite many efforts and intensive research, PTB control is still controversially discussed and diagnostic and immunoprophylactic tools lack great limitations. Thus, models play a crucial role in understanding the pathogenesis of infection and disease, and in testing novel vaccine candidates. Here, we review the potential and limitations of different experimental approaches currently used in PTB research, focusing on laboratory animals and cell based models. The aim of this review is to offer a vision of the models that have been used and what has been achieved or discovered with each one so that the reader can choose the best model to answer their scientific questions and prove their hypotheses. Also, we bring forward new approaches that we consider worth exploring in the near future.

Wounds represents a medical problem that contribute importantly to patient morbidity and to the healthcare costs in several pathologies. In Hidalgo, Mexico, Bacopa procumbens plant has been traditionally used for wound healing care for several generations; in vitro and in vivo experiments were design to evaluate the effects of bioactive compounds obtained from B. procumbens aquoethanolic extract and to determine the key pathways involved in wound regeneration. Bioactive compounds were characterized by HPLC- QTOF-MS and proliferation, migration, adhesion, and differentiation studies were done on NIH/3T3 fibroblasts. Polyphenolic compounds from Bacopa procumbens (PB) regulated proliferation and cell adhesion; enhanced migration reducing the artificial scratch area; and modulated cell differentiation. PB compounds were included in a hydrogel for topical administration on rat excision wound model. Histological, histochemical and mechanical analysis showed that PB treatment accelerates wound closure in at least 48 h; reduce inflammation, increasing cell proliferation and deposition and organization of collagen in earlier times. These changes resulted in the formation of a scar with better tensile properties. Immunohistochemistry and RT-PCR molecular analyses demonstrated that treatment induces: i) overexpression of transforming growth factor beta (TGF-β); and ii) the phosphorylation of Smad 2/3 and ERK1/2, suggesting the central role of some PB to enhance wound healing, modulating TGF-β activation.

Based on the historical research on the shape of armor in Ming Dynasty, this paper explores the shape characteristics of general armor in Ming Dynasty in China through field research on the general stone statue of Ming Xiaoling Mausoleum in Nanjing. Through Ming Xiaoling Mausoleum general stone carving 3D animation technology restoration project, virtual material heritage practice is carried out. Through the modeling of the general stone statue in Ming Xiaoling Mausoleum by MAYA and Zbrush, UE4 realizes the construction of scenes and the output of interactive effects, so as to explore a mode of application engine animation that can preserve and propagate general stone carving in Ming Xiaoling Mausoleum.

Ochna kibbiensis (Family: Ochnaceae) has been employed in ethnomedicine for the treatment of malaria, and inflammation among others. The aim of this study was to isolate and characterize prophylactic antimalarial agents from the leaves of O. kibbiensis against Plasmodium berghei, in vivo and in silico. The median lethal dose (LD50) of the methanol extract and its fractions (n-hexane, dichloromethane, ethylacetate and n-butanol) was determined according to Lorke’s method while the antimalarial effect of the extract and its fractions was investigated according to the method described by Peters prophylactic test using Chloroquine-sensitive Plasmodium berghei (NK65). All the extract/fractions exhibited LD50 values ≥ 5000 mg/kg with the exception of the n-butanol fraction (1702.94 mg/kg) which indicate that the plant is non-toxic. Dichloromethane fraction exhibited significant (p&lt;0.05) and dose-dependent prophylactic effect with 47.62, 85.12 and 100.0 % prophylaxis (at 500, 250 &amp; 125 mg/kg) while the least effect was observed by the n-butanol fraction with percentage prophylaxis of 64.29 and 76.19, respectively; the standard drug, pyrimethamine had 95.24 % prophylaxis. Based on the result obtained, dichloromethane fraction of O. kibbiensis was subjected to chromatographic purification which led to the isolation of a mixture of two compounds identified as stigmasterol and β-sitosterol by analysis of the NMR spectral data and comparison with existing literature; the compounds exhibited good binding affinities (- 5.129 and - 4.889 kcal/mol) against pfLDH and favorable ADMET profile. In conclusion, the leaf of O. kibbiensis have demonstrated a significant prophylactic antimalarial activity and the two known steroids (stigmasterol and β-sitosterol) isolated from the dichloromethane fraction for the first time.

The objective of this research is to analyze the effect of determinants of Business ethics (HR management ethics, ethics in corporate governance, and ethics in sales & marketing) on the organizational performance of the high-tech industry. The study further examines the influence of multiple serial mediations of human, structural, structural, and relational capital on the connection between Business ethics and organizational performance. Additionally, this research examines how technological change moderates the relationship between Business ethics and organizational performance. Data was collected from the information technology sector in various cities of South Asian countries through structured questionnaires. PLS-SEM modeling was used via Smart-PLS 4.0 software for analysis. The hypothesized & modified measurement and structural model were validated using the HTMT matrix, Fornell-Larcker criterion, R-square values, f-square values, outer loading, construct reliability and validity, path coefficient analysis, Blindfolding, and predictive relevance. The research results suggest that ethics in corporate governance, HR management ethics, and ethics in sales & marketing have a notable positive effect on business ethics, leading to a substantial and affirmative impact on the organizational performance of the high-tech industry. The findings further suggested that dimensions of intellectual capital (human capital, structural capital & relational capital) significantly moderate between exogenous and endogenous constructs. Moreover, technological change significantly & positively moderates the relationship between Business ethics and organizational performance of the high-tech industry. In conclusion, this research provides insights into how these variables interact and what potential mechanisms act upon them. Organizations can make informed decisions about improving their performance and ethical standards by understanding these relationships. This research offers substantial theoretical and managerial implications to research scholars and industry practitioners.

The COVID-19 pandemic affects not only physical health but also deteriorates mental health resulting in sleep problems, depression, and traumatic stress. Our research investigates the level of posttraumatic stress, perceived social support, opinions on positive and negative consequences of the pandemic, sense of security, and sense of meaning among nurses in the face of new and not fully understood global epidemiological phenomena. For this purpose, computer-assisted web interviewing methods were conducted between May 1 and May 15, 2020. Participating nurses completed the following research tools: The Impact Event Scale-Revised (IES-R), The Multidimensional Scale of Perceived Social Support (MSPSS), The Changes in Outlook Questionnaire (CIOQ), The Safety Experience Questionnaire (SEQ) and The Meaning in Life Questionnaire (MLQ). Three hundred and twenty-five nurses working throughout Poland joined the study of an average age of 39.18 ± 11.16 years. The average overall IES-R score in the study group was 1.78 ± 0.65. Among the dimensions of traumatic stress, the highest score was obtained in the dimension Avoidance 1.86 ± 0.73, then in the dimensions Hyperarousal 1.8 ± 0.78 and Intrusion 1.74 ± 0.83. Amongst studied nurses, the highest support rates were provided by significant others (22.58 ± 5.22), then from friends (21.91 ± 5) and family (21.45 ± 4.4). Among the surveyed nurses, higher average scores were noted in the subscale measuring positive psychological changes (18.56 ± 4.04). In contrast, a higher average level of assessment was noted on the Reflection on the safety dimension (4.21 ± 0.49). The mean MLQ score was 5.33 ± 0.87. A slightly higher result was observed in the subscale Presence (5.35 ± 1.14). The results of the research implemented during the period of severe psychological pressure associated with the COVID-19 pandemic provided information on symptoms of traumatic stress in the examined group of nurses. Their sense of security has been lowered and accompanied by an intensified reflection on issues concerning security. However, the sense of meaning (currently felt) in life remains higher than the tendency to searching for it. The surveyed nurses perceive individual support from the so-called significant others (apart from family and friends). They see positive changes resulting from painful experiences related to the COVID-19 pandemic, which can be characterized by adaptation in the form of posttraumatic growth.

The progress in markerless technologies is bringing clinicians tools to rapidly evaluate tests such as Timed Up and Go (TUG) without compromising the time of the assessment, yet it raises questions about the potential trade-off in accuracy compared to traditional marker-based systems, suggesting that the precision of these evaluations is not yet conclusively established. The OpenCap system is an easy tool to process 3D kinematics with two iPhone cameras placed in front of the subject. Previous research has primarily focused on walking and movement towards the cameras with the subject facing the cameras (WF) and thus has been unable to disentangle the differences in the movement directions. We have compared the OpenCap system with a standard marker-based system for both walking directions. In OpenCap, we found significantly worse results capturing walking facing away from the cameras (RW). Compared to the marker-based system, our findings indicate troubles measuring kinematic parameters but provide good accuracy in measuring spatial-temporal parameters. These insights pave the way for refining markerless assessment technologies, potentially enhancing their utility in clinical settings.

This comprehensive study delves into the implementation and effectiveness of the flipped classroom model in engineering EMI (English as a Medium of Instruction) courses in Taiwan. Situated within the strategic framework of Taiwan's Bilingual Nation 2023 policy, this research aims to enhance the global competitiveness of Taiwan's semiconducting manufacturing engineering sector. The study’s primary focus is on understanding the perceptions and learning outcomes of EFL (English as a Foreign Language) students in engineering courses. Through a methodical approach using descriptive statistics and chi-square tests, the study analyzes data from 33 junior engineering students specializing in mechanical and mechatronic fields. The findings highlight a significant positive influence of the flipped classroom model on various aspects of student learning, including increased engagement, heightened creativity, and enhanced problem-solving skills. Additionally, the study emphasizes the critical role of timely L1 support in facilitating effective learning in EMI settings. These outcomes not only demonstrate the flipped classroom's viability as a sustainable educational approach but also provide crucial insights for educators and policymakers. By aligning cutting-edge teaching methods with the evolving needs of engineering education, this study contributes to the discourse on educational innovation. It ultimately guides the development of future engineering programs that cater to diverse student needs and fosters the cultivation of skilled engineering professionals.

In this study, we analyse if in-utero exposure to Ramadan fasting period is negatively associated with child nutrition? The data for the analyses come from a retrospective assessment of 924,198 children from 103 demographic and health surveys (DHS) across 56 countries during the period 2003-2020. Considering the month-long Ramadan exposure as a natural experiment, we implement an intent-to-treat framework, comparing outcomes among individuals who were exposed to Ramadan at any time in-utero to those who were not exposed. Our findings do not show significant evidence to conclude that in-utero exposure to Ramadan fasting period is negatively associated with child nutrition. On the contrary, except for stunting in children who had in-utero exposure to Ramadan during the first trimester, among Muslims, we find slightly better nutritional outcomes among children exposed in-utero to Ramadan period. The better nutritional outcomes among children exposed in-utero can be attributed to high nutritious food intake and better hygienic practices during holy months of Ramadan compared to usual months. Our main results are robust to multiple robustness checks.

Nymphaea lotus L. is the medicinal plant that has long been used as food, cosmetic and traditional medicines in Africa and Asia since the ancient time. Its flavonoids and other interesting phytochemical compounds from rhizome, leaf, and the whole flowers have been reported in the previous published researches. However, stamens, which are essential for reproductive functions, may also represent new alternative sources of potential antioxidant flavonoids as investigated in this study. The innovative green chemistry method i.e. ultrasound-assisted extraction (USAE) as well as macroporous resin (MPR) purification procedure were employed in this current research. The optimal ultrasound-assisted extraction condition is 90 % (v/v) aqEtOH with 34.65 khz ultrasonic frequency and 46 minutes of extraction time. Comparing with heat reflux extraction (HRE) conventional method, the significant gain of 1.35 total flavonoids content was obtained using optimized USAE conditions, jumping to 2.80 when this USAE associated with MPR purification. Not only in vitro cell free antioxidant activity of N. lotus stamen extracts, but also in cellulo antioxidant investigation using yeast model showed the same trend to indicate that the best antioxidant flavonoid can be found in USAE coupled with MPR purification. Moreover, the key antioxidant genes expression in yeast model such as SIR2 and SOD2 were also expressed at the highest level in yeast cell treated with the extract from USAE together with MPR purification. Consequently, it can be seen that the USAE combined with MPR purification can help to enhance the flavonoids antioxidant potential of the stamens extract from this medicinal species.

Epidermal Growth Factor Receptor (EGFR) tyrosine kinase is a cell surface receptor whose overexpression has been associated with different types of cancers including brain cancer (glioblastoma multiforme). The ability of the extract of Scutellaria baicalensis to inhibit the proliferation of malignant glioma cells have been reported. Thus, in this study we report the identification of 307 bioactive constituents responsible for the anti-glioblastoma multiforme effect from S. baicalensis using in silico studies such as molecular docking, binding free energy calculations, pharmacophore modelling, induced-fit docking, gene enrichment analysis, molecular dynamic simulations and ADMET predictions. A total of 307 chemical constituents of S. baicalensis were screened and the top 10 scoring compounds indicated different binding affinities ranging from -9.010 to -6.427 kcal/mol towards the EGFR tyrosine kinase; Ganhuangenin, 5,7,2',5'-tetrahydroxyflavone, (2R)-2-(2,6-dihydroxyphenyl)-3,4-dihydro-2H-chromene-5,7-diol, and tenaxin I possess higher binding affinities (-9.010 to -8.649 kcal/mol) compared to the standard ligand, erlotinib having -8.539 kcal/mol. The compounds interacted with amino acids of clinical importance such as MET 769, GLU 738, THR 766 via H-bond. The structural features involved in the interaction with the target were mostly two aromatic rings, H-bond donors and acceptors and some hydrophobic interactions which varies between the ligands. Better docking scores in the induced-fit docking further validates the inhibitory potential of the compounds against the flexible protein. All the top-scoring ligands from S. baicalensis had zero Lipinski violation and also obeyed other drug-likeness rules by Ghose, Veber, Egan, and Muegge with the exception of breviscapine. Interestingly, all the compounds are not likely to be hepatotoxic, mutagenic, or cytogenic, making them potentially safe as anti-cancer agents.

As renewed interest in human space-exploration intensifies, a coherent and modernized strategy for mission-design and planning has become increasingly crucial. Biotechnology has emerged as a promising approach to increase mission resilience, flexibility, and efficiency by virtue of its ability to efficiently utilize in situ resources and reclaim resources from waste streams. Since its infancy during the Apollo years, biotechnology, and specifically biomanufacturing, have witnessed significant expansions of scope and scale. Here we outline four primary mission classes, on Luna and Mars, that drive a staged and accretive biomanufacturing strategy. Each class requires a unique approach to integrate biomanufacturing into the existing mission architecture and so faces unique challenges in technology development.These challenges stem directly from the resources available in a given mission class – the degree to which feedstocks are derived from cargo and in situ resources – and the degree to which loop-closure is necessary. We see that as mission duration and distance from Earth increase, the benefits of specialized sustainable biomanufacturing processes increases. Here we present a strategic approach, guided by technoeconomics, to development, testing, and deployment of these technologies serves to nucleate the larger effort of supporting a sustained human presence in space. The processes needed for each scenario spans the technical breadth of synthetic biology to design engineering, from sophisticated genetic tailoring of chassis-organisms to building scalable, automated, easily operable bioreactors and processing systems. As space-related technology development often does, these advancements are likely to have profound implications for the creation of a stable, resilient bioeconomy on Earth.

In this study, we have first studied the trend in meteorological data from the Harmaleh, Vanai and Farsesh stations in the 50-year period in the Dez catchment area. The meteorological data will be then forecasted using SWAT and Mann-Kendall. Forecasting the results in the Mann-Kendall and SWAT model has been done using the code written in MATLAB software and RCP (4.5, 8.5) scenarios, respectively. Studying the results of the trend in the data of meteorological stations in this catchment area indicated that these two parametric and non-parametric methods have been used to determine trends in meteorological data. The results of the parametric method are positive in all meteorological parameters. Non-parametric method over a period of 50 years shows the presence of trends in the data. The comparison on the forecasting results at maximum temperature suggested that during summer, we will see an increase in temperature compared to the ground state in all three forecasts. The results of the minimum temperature forecast show a decrease in the minimum increase during the winter and the precipitation forecast indicates that at the end of autumn (Nov) precipitation decreased by 20 mm in the Mann-Kendall and 4.5 RCP while RCP8.5 suggests the increase in precipitation compared to the ground state. Studying the runoff forecast results using SWOT show that at the end of winter (Feb) and almost all spring (Mar, Apr) a decrease of about 40%, 15% and 14% will be seen, respectively

The pinning force density FpJc,B=Jc×B (where Jc is the critical current density and B is the applied magnetic field) is one of the main parameters that characterize the resilience of a superconductor to carry a dissipative-free transport current in an applied magnetic field. Kramer (1973 J. Appl. Phys. 44 1360), and Dew-Hughes (1974 Phil. Mag. 30 293) proposed a widely used scaling law for the pinning force density amplitude: FpB=Fp,max×p+qp+qppqq×BBc2p×1-BBc2q, where Fp,max, Bc2, p, and q are free-fitting parameters. Since the late 1970-s till now, several research groups have reported experimental data on the dependence of Fp,max on the average grain size, d, in Nb3Sn-based conductors. Godeke (2006 Supercond. Sci. Techn. 19 R68) proposed that the dependence obeys the law Fp,maxd=A×ln1d+B. However, this scaling law has several problems, for instance, the logarithm is taken from a non-dimensionless variable, and Fp,maxd&lt;0 for large grain sizes, and Fp,maxd→∞ for d→0. Here, we reanalysed the full inventory of publicly available Fp,maxd data for Nb3Sn conductors and found that the dependence can be described by Fp,maxd=Fp,max0×exp-dδ law, where the characteristic length, δ, varies within a remarkably narrow range, that is, δ=175±13 nm, for samples fabricated by different technologies. The interpretation of the result is based on the idea that the in-field supercurrent flows within a thin surface layer (thickness of δ) near the grain boundary surfaces (similar to London’s law, where the self-field supercurrent flows within a thin surface layer with a thickness of the London penetration depth, λ, and the surface is a superconductor-vacuum surface). An alternative interpretation is that δ represents the characteristic length of the exponential decay flux pinning potential from the dominant defects in Nb3Sn superconductors, which are grain boundaries.

The Oxford English Dictionary includes 17 definitions for the word “model” as a noun and other 11 as a verb. Therefore, context is necessary to understand the meaning of the word model. For in-stance, “model railways” refer to replicas of railways and trains at a smaller scale and a “model student” refers to an exemplar individual. In some cases, a specific context, like cancer research, may not be sufficient to provide one specific meaning of a model. Even if the context is narrowed, specifically to the research related to the tumour microenvironment, a “model” can be understood in a wide variety of ways, from an animal model, to a mathematical expression. This paper presents a review of the different “models” of the tumour microenvironment grouped by the different def-initions of the word into four categories: model organisms, in vitro models, mathematical models, and computational models. Then, the frequency of different meanings of the word “model” related to the tumour microenvironment is measured from the number of entries in the MEDLINE database of the United States National Library of Medicine at the National Institutes of Health. The frequency of the main components of the microenvironment and the organ-related cancers modelled are also assessed quantitatively with specific keywords. Whilst animal models, in particular xenografts and mouse models are the most common used “models”, the number of entries have been slowly de-creasing. Mathematical models, prognostic and risk models follow in frequency and these have been growing in use.

Power systems have been going through a barrage of transformations due to the recent developments in the field, such as deregulation and restructuring of the electric power supply chain, the proliferation of distributed generation (DG), and advancements in information and communications technologies. These have significantly impacted the approach to the planning, design, and operation of active distribution networks or systems. Due to this constant change, the system has become more complex to plan, maintain, and control. In this paper, the benefits, and challenges of active distribution systems relative to traditional passive and active distribution systems are evaluated and investigated while the management and operational characteristics of demand-side resources in Active Distribution Systems (ADS) are studied. In a typical ADS, there exist several vulnerabilities and threats that eventually pose a challenge in the control and automation of substations. These vulnerabilities and threats are reviewed, and potential mitigation measures are suggested. Also in this paper, the communication technologies, and their implementation in terms of control and automation capabilities in active distribution networks are also studied. From this work, it is concluded that communication technologies play an integral role in the realization of a more active distribution networks and that the internet of energy (IoE) is a major player in ADS in the reduction of faults due to human error, fast responses, and improving the stability of power supply. Cyber threats are also and will still be a continuous challenge in smart metering technologies and in substation automation systems (SAS) which will require frequent evaluation and mitigation measures so as not to prevent the power supply system from collapsing.

Acacia nubica is well-adapted to harsh conditions and offers valued socio-economic and environmental benefits. This research studied seed germination and seedling growth of A. nubica in vitro in response to the application of different concentrations of sodium hypochlorite, sucrose, and Murashige and Skoog (MS) medium. The synchrony, percentage, and rate of germination of A. nubica seed were studied. Seedling development was assessed by measuring the shoot, root, and number of nodes. Sodium hypochlorite at 10% produced the maximum germination percentage, while 5% induced a faster and more uniform emergence. Sucrose has various effects on seed emergence and germination depending on the concentrations; 30 g/L elicited the highest germination, while 10 g/L improved seed emergence rate with higher uniformity. The highest seed germination was achieved on ¼-MS medium, although 0-MS strength recorded faster and more synchronized germination. The development of A. nubica seedlings was influenced by MS medium strengths and sucrose concentrations. Full MS medium produced the highest shoot length and the highest vigor index with the addition of 20 g/L sucrose and the maximum root length with 50 g/L sucrose. Also, 30 g/L sucrose gave the maximum number of nodes and the maximum root/shoot ratio. However, ½-MS strength yields the highest seedling biomass with 30 g/L sucrose. This is the first successful report on the seed germination and seedling growth of A. nubica in vitro.

In this review paper, the occurrence in the plant kingdom and the biological activities associated to two specific phenyl-ethanoid glycosides i.e., leucosceptoside A and leucosceptoside B, were shown and discussed. This is the first work ever done on such subject. Analysis of the literature data clearly indicates that leucosceptoside A is much more common in plants and exerts many more biological activities than leucosceptoside B even if this also presents some important elements. All of this was widely discussed in this paper.

The present work evaluates the food effect on the absorption of rivaroxaban (Riva), a BCS II drug, from the orally administered commercial immediate-release tablet (Xarelto IR) using physiologically based pharmacokinetic (PBPK) and conventional in vitro- in vivo correlation (IVIVC) models. The bioavailability of Riva upon oral administration of Xarelto IR tablet is reported to exhibit a positive food effect. The PBPK model for Riva was developed and verified using the previously reported in vivo data for oral solution (5 and 10 mg) and Xarelto IR tablet (5 and 10 mg dose strength). Once the PBPK model was established, the in vivo performance of the tablet formulation with the higher dose strength (Xarelto IR tablet 20 mg in fasted and fed state) was predicted using the experimentally obtained data of in vitro permeability, biorelevant solubility and in vitro dynamic dissolution data using United States Pharmacopeia (USP) IV flow-through cell apparatus. In addition, the mathematical IVIVC model was developed using the in vitro dissolution and in vivo profile of 20 mg strength Xarelto IR tablet in fasted condition. Using the developed IVIVC model, the pharmacokinetic (PK) profile of the Xarelto IR tablet in fed condition was predicted and compared with the PK parameters obtained via the PBPK model. A virtual in vivo PK study was designed using a single-dose, 3-treatment cross-over trial in 50 subjects to predict the PK profile of the Xarelto® IR tablet in the fed state. Overall, the results obtained from the IVIVC model were found to be comparable with that from the PBPK model. The outcome from both the model pointed to the positive food effect on the in vivo profile of the Riva. The developed models thus can be effectively extended to establish bioequivalence for the marketed and novel complex formulations of Riva such as amorphous solid dispersions.

Gentiopicroside (GPS) is a leading component of several plant species from Gentianaceae botanical family. As a compound with plenty biological activities and a component that is often consumed in dietary supplements and herbal drugs, GPS has an important role in the regulation of physiological processes in humans. Recent studies on the type 2 receptors shed new light on GPS applications showing its agonistic properties that could be meaningful in the future therapeutic strategies of Parkinson’s disease, thyroid disorders or cancer states. This review aims to collect previously published reports on the biological properties of GPS as a single compound that were confirmed by in vitro and in vivo studies, and to draw attention at the newly discovered role of this bitter-tasting secoiridoid as a type 2 receptor agonist. Thanks to these properties, the research on this substance could be revisited.

Confined masonry (CM) is a construction system which consists of masonry wall panels enclosed by vertical and horizontal reinforced concrete confining elements. The presence of these confining elements distinguishes CM from unreinforced masonry system and makes this technology suitable for construction of structures in regions subjected to intense seismic or wind actions. CM construction has been used in many countries and regions, and has performed well in past earthquakes. The purpose of the paper is to review past research studies related to the seismic in-plane and out-of-plane behaviour of CM structures. The authors have identified the key design and construction parameters which were considered in past research studies and have performed statistical analyses to establish their influence on the seismic performance of CM buildings. For the purpose of this study the authors have compiled databases of previous experimental studies on CM wall specimens which were used for statistical analyses. Finally, the paper discusses research gaps and needs for future research studies which would contribute to the understanding of seismic behaviour and failure mechanisms of CM walls.

Between 1942 and 1945, Jewish inmates of a forced labour camp and later Auschwitz subcamp at Blechhammer (Blachownia Śląska, Upper Silesia) worked alongside British prisoners of war on the construction site of a giant synthetic fuel facility, the Oberschlesische Hydrierwerke. The paper examines the multifaceted forms of interaction between these two groups, who were situated at the opposite ends of a spectrum ranging from high survival rates to certain death. By reframing the Jewish inmates’ perceptions of the POWs, it seeks to shed new light on a controversial debate on the nature of the relationship between them and British prisoners. The paper argues that important aspects have been missing from this debate, as the Jewish inmates were not sufficiently represented and not viewed as active protagonists. The relations between Jews and British POWs were not one-sided, but rather interdependent in complex ways. Both groups used these contacts to gain strategic information on the war and jointly contributed to the Allied resistance effort. The barter with British POWs played a crucial role in the collective and individual survival strategies of Jewish inmates, whereas the British increasingly depended on the Jewish inmates to procure basic foods when German rations ceased to be allocated. An analysis of the effects of British aid giving showed that the actual impact on the physical survival of the emaciated inmates was negligible. However, these humanitarian gestures significantly boosted their mental strength and equally helped them to cope better with post-traumatic stress disorders after the war. Altogether, the British were encouraging symbols of resistance against the Nazi regime in the eyes of the inmates. Negative experiences were rarely corroborated and were often linked to poor English language skills or a stronger identification with other nationalities.

Cyanobacteria are prokaryotes whose taxonomy follows the same rules of a code (the International Botanical Nomenclature Code, IBNC) built for eukaryotic photosynthetic organisms. Hence, names of cyanobacteria follow the same rules and are assigned to biological entities (species) that should correspond to eukaryotic species. The main difficulty in the current situation is that the species concept in eukaryotes is based theoretically mainly on the biological species concept, that is centered on genetic exchange through sexual reproduction or lack of them. However, as shown, this difference is important from a theoretical point of view, but also in eukaryotes, the boundaries between different species are very rarely checked experimentally by direct observation of sexual barriers and hybridization events. The main concept for species delimitation is hence that related to morphology and, more recently and always in relation to morphology, DNA sequences. The introduction of distances obtained from matrixes of aligned sequences in the framework of a barcoding project provides a quantitative interpretation of species delimitation in relation to genetic distance that can be used both in eukaryotes and prokaryotes. However, the introduction of quantitative criteria needs the definition of distance thresholds to identify the boundaries between different species and, for doing that, it is necessary to test the distance thresholds in models of traditionally defined and recognized species. An alternative approach may be the comparison of the molecular distance (quantitative approach) to data about the capability of strains/species to exchange genetic information. Unfortunately data about this last question is still scarce. The adoption of molecular criteria to check species boundaries based on morphological characters has proved particularly challenging in cyanobacteria: a known example is provided. In conclusion, the only possible approach appears to be the association of molecular data to the increase of available data about the cell structure and the variation thereof in different physiological situations, particularly at the ultrastructural level. A further necessity is the check of the typus for a large number of cyanobacteria species, often based on old basionyms. In many of these cases the typus is often a drawing and more rarely a herbarium specimen or a microscope slide. In many cases an epitypification or a neotypification appears to be necessary.

Preeclampsia is a multifactorial cardiovascular disorder diagnosed after 20 weeks of gestation that is the leading cause of death for both mothers and babies in pregnancy. The pathophysiology remains poorly understood due to variability and unpredictability of disease manifestation when studied in animal models. After preeclampsia, both mothers and offspring have a higher risk of cardiovascular disease (CVD) including myocardial infarction or heart attack and heart failure (HF). Myocardial infarction is an acute myocardial damage that can be treated through reperfusion, however, that therapeutic approach leads to ischemic/reperfusion injury (IRI) often leading to HF. In this review, we compared the current in vivo, in vitro and ex vivo model systems used to study preeclampsia, IRI and HF. Future studies aiming at evaluating CVD in preeclampsia patients could benefit from novel models that better mimic the complex scenario described in this article.

Immunotherapy with stereotactic body radiotherapy (SBRT), low-dose antiangiogenics, immune adjuvants, nanomedicine, or other combinations will likely play a lead role in managing malignancies soon. Presently, its benefit extends to about 12% to 20% of patients, in the background of possible recurrence eventually and the toxicities, including in non-responders. Stereotactic body radiotherapy (SBRT) not only eliminates the indexed lesions, but recently, the evidence is accumulating about its systemic abscopal effects. It needs to be evolved to a dependable in situ therapeutic vaccine production and to activate short- and long-term memory immune lymphocytes. The in-situ immune cascade happens with the ability of SBRT to generate Tumor-specific neoantigens and neoepitopes, which enhance the activation of antigen-presenting cells, invoke and restore the competence of Tumor-infiltrating lymphocytes, resulting in cancer cell lysis. This cell lysis, in turn, can generate further neoantigens and epitopes, imparting a virtuous cycle that is the hallmark of effective vaccines. Additionally, SBRT can synergistically enhance the other in situ vaccination strategies, concurrent in vitro vaccines or nanomedicines, making it a primary tool for sensitizing even the “cold” tumors for immunotherapy. The present proposed hypotheses, primarily based on a preclinical literature review, focus on the critical aspects of the in-situ vaccination generation capability of SBRT when used in pulsed, cyclical, or intermittent endothelial-sparing single dose schedules along with immunotherapy and other supportive measures. This schedule is categorized as in situ vaccine dose (ISVD) radiotherapy (RT) (distinguishable from the standard therapeutic SBRT schedule) in metastatic cancer settings after standard /first-line therapies.

This paper exposes the initial part of a research consisting in a need analysis carried out by the Romanian partner in the Erasmus+ "Media Education for Aware Adults" project, regarding digital competences and media education of adult educators or trainers. After a short introduction on the subject, in the paper are presented the main findings of the desk research, and two focus group sessions, first one for identifying the necessary digital competences of adult educators, and second one for identifying the elements that educators need in order to adequately support adults in their learning process, especially in relation to the digital environment. The results of the initial research will lead to the development of the main intellectual outputs, namely the digital competences framework, handbook, online platform and training material on digital and media education. In their development will be taken into account, on the one hand, the needs identified in the initial research, and, on the other hand, the need for a sustainable approach to all activities, resources and outputs produced, as well as education itself, this goal being assumed through the project.

In this paper, we propose a new mathematical model based on the association between susceptible and recovered individual, where the association between susceptible and recovered individual is disturbed by white noise. This model is based on demographic changes and is used for long term behavior. We study the stability of equilibria of the deterministic model and prove the conditions for the extinction of diseases. Then, we investigate and obtain the critical condition of the stochastic epidemic model for the extinction and the permanence in mean of the disease with the white noise. To verify our results, we present some numerical simulations for real data related to disease.

Policies are adopted and implemented to achieve specific goals. In this regard, the Government of Zambia in 2019 adopted the higher education policy with many objectives which include, the expansion of access to higher education; reduction of gender and other forms of inequity in accessing higher education; the improvement of quality of higher education by increasing funding to higher education institutions, construction, and repair of infrastructure in higher and improvement in the provision of learning materials in higher education institutions (HEIs).This paper, therefore, sought to evaluate the higher education policy of 2019. The four criteria were used namely; effectiveness, equity, policy sustainability, and consistency. Other principles such as political and social acceptability of a policy were not used because the policy is already adopted and being implemented. Further, the principle of efficiency was not used because it would have been problematic to gauge the expenditure against the outcomes.The findings have revealed that the policy to some extent has been effective; some of the objectives such as increased access to higher education and reduction of inequality have been partially achieved. It has been established that the number of students pursuing higher education has been increased to 114,049 in 2020 from 91,969 in 2017. Further, in 2021, 48.5% of scholarships in public universities were awarded to female students while 51.5% were awarded to female students. Further, more students are encouraged to pursue science, technology, engineering, and mathematics (STEM); and more women are pursuing studies in STEM-related fields. However, the policy has not helped to achieve the quality of higher education as funding in public HEIs has not improved. Further, infrastructure remains very poor and inadequate; and access to update and relevant learning materials also remains a challenge in HEIs. However, the policy seems to be duplicated by the recent re-launched Technical Education Vocation Entrepreneurship Training (TEVET) national policy.Given the above findings, it has been recommended that the government among other things improve funding and build infrastructure in public HEIs. There is also a need to harmonise the TEVET national policy with the higher education policy.

Keeping in mind the increasing trend and need for serious games in science education, we have done a systematic literature review. These papers show the trends and patterns of research carried out in this field from the year 2011 to 2020. Specifically, we investigated country-wise concentration and the most common evaluation methods. Literature is reviewed from IEEEexplore, Springer, and Scopus. Moreover, we discussed the role of Augmented Reality(AR) games in teaching physics. Lastly, we have discussed the positive and negative aspects of serious games in science education in particular, and the trend of using serious games in the past decade in education in general.

Soups show diverse health functions, which should be related with their nutrient profiles. NMR spectroscopy is a robust, sensitive and rapid method to unveil or identify the chemical composition of food or food-derived metabolites. In the current study, 1H-NMR spectroscopy approach was applied to identify the metabolic profiling of two kinds of home-cooked freshwater fish soups (crucian carp and snakehead fish) before and after in vitro gastrointestinal digestion. The nutritional profiles of these two kinds of soups were identified at first. With the help of OPLS-DA method (Orthogonal Partial Least Squares Discriminant Analysis), these two different kinds freshwater fish under different states were completely discriminated. The metabolites changes in digested fish soups could reveal the information of chemical compounds which play important roles in the body. Furthermore, the metabolic patterns of different kinds of fish soups could reflect the various nutrition profiling characteristics for dietary therapy.

This study investigates the stochastic dynamics of hepatitis B virus (HBV) infection using a newly proposed stochastic model. Contrary to deterministic models that fail to encapsulate the inherent randomness and fluctuations in biological processes, our stochastic model provides a more realistic representation of HBV infection dynamics. It incorporates random variability, thereby acknowledging the changes in viral and cellular populations and uncertainties in parameters such as infection rates and immune responses. We examine the solution's existence, uniqueness, and positivity for the proposed model, followed by a comprehensive stability analysis. We provide the necessary and sufficient conditions for local and global stability, offering deep insight into the infection dynamics. Furthermore, we utilize numerical simulations to corroborate our theoretical results. This research provides a robust tool for understanding the complex behavior of HBV dynamics, contributing significantly to the ongoing quest for more effective HBV control and prevention strategies.

This paper investigates the effect of the Internet on tax revenue instability, notably through the international trade channel. It has used a sample of 142 countries over the period 1995-2017, and relied primarily on the two-step system Generalized Methods of Moments (GMM) estimators (but also incidentally on the Error Component Two-Stage Least Squares estimator). Tax revenue instability is primarily measured by the instability of non-resource tax revenue, but also by the instability of total tax revenue (for robustness check). The findings indicate that the Internet exerts a negative effect on tax revenue instability. Interestingly, this effect genuinely translates through the international trade channel, regardless of the measure of tax revenue instability considered. Countries enjoy a higher negative effect of the Internet on tax revenue instability as they enjoy a greater participation in international trade. These findings, therefore, add to the potential benefits of the Internet adoption (e.g., strengthening countries' participation in international trade, enhance their tax revenue performance and promote tax reform, including in developing countries) by showing that it could also help to stabilize tax revenue, particularly through the degree of countries' participation in international trade.

In plants and animals, endogenous biological molecules, termed damage-associated molecular patterns (DAMPs) or alarmins, are released by damaged, stressed or dying cells following abiotic stress such as radiation and drought stress. In turn, a cascade of downstream signaling events is initiated leading to the up-regulation of defense-related genes. In the present study, in an effort to investigate the conservation status of the molecular mechanisms implicated in the danger signaling, thorough in silico phylogenetic and structural analyses of the effector biomolecules were performed in taxonomically diverse plant species. On the basis of our results, the defense mechanisms appear to be largely conserved within the plant kingdom. Of note is our finding that the sequence and/or function of several components of these mechanisms were found to be conserved in animals, as well.

Raru’s plants bark has long been used as traditional medicine in Batak’s tribe. Raru’s bark is derived from several trees that are usually used in a mixture in Batak traditional beverages. This bark is generally used as antidiabetic remedies. This study aims to combine the rarus’s bark extract and mocaf activated-carbon (MAC) in order to study antidiabetics in rats. The combination of raru’s bark extract and MAC were tested on male rats as of Sprague Dawley strain for testing antidiabetic bioactivity. The result showed that antidiabetic activity of raru’s extract and MAC exposed the antidiabetic level declines in rat’s blood. The various treatments of different concentration ratios of raru’s extract and MAC useful in the experiments showed that the levels of blood level reduction were slightly different (14-21%). The raru’s extract pure was observed more effective in decreasing the blood glucose level in rat’s blood, in comparison the positive control. The mixture of raru’s extract and MAC with 75:25 ratio is better than 50:50 ratio. The involvement of MAC in the alleged antidiabetic agent did little in improving the blood glucose level decrease in rat’s blood. Raru’s extract and MAC indicate its potential utilization as an antidiabetic agent.

The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was isolated in 2012 and is well known to cause the respiratory syndrome. The orf1ab gene is known to mediate MERS-CoV replication. In this study, we have discussed the in silico prediction of potential siRNAs targeting MERS-CoV-orf1ab gene for antiviral therapeutics. To identify the potential siRNAs, various factors were considered. We have excluded the siRNAs with off-target effects and potential binding with human mRNAs. By using available softwares, total twenty-one functional, off-target reduced potential siRNA were selected from four hundred and sixty-two siRNAs based on greater potency and specificity. We have tested only seven siRNAs initially to evaluate their performance by reverse transfection approach by lipofectamine mediated delivery in Vero cells. The evaluation results showed no cytotoxicity at various concentrations of siRNAs used. The results obtained in this study provided preliminary information about the cytotoxicity which will help us to further evaluate siRNAs in other cell cultures to find out the replication inhibition efficiency of MERS-CoV. Finally, it is concluded that the in silico prediction and designing resulted in filtration and selection of potential siRNAs with high accuracy, efficiency, and strength which can be further utilized for the development of oligonucleotide-based therapeutics.

This paper employs the two-step procedure developed by Cheung and Ng (1996) to analyze the causality-in-mean and causality-in-variance between the housing and stock markets of the UK. The empirical findings make two key contributions. First, although previous studies have indicated a one-way causal relation from the housing market to the stock market in the UK, this paper discovered a two-way causal relation between them. Second, a causality-in-variance as well as a causality-in-mean was detected from the housing market to the stock market.

Introduction: studies in the last two decades have found declining snake populations in both temperate and tropical sites, including informal reports from Drake Bay, Costa Rica. Objective: to investigate if reports of decreasing snake populations in Drake Bay had a real basis, and if environmental factors, particularly temperature, rain and light, have played a role in that decrease. Methods: we worked at Drake Bay from 2012 through 2017 and made over 4000 h of transect counts. Using head flashlights we surveyed a transect covered by lowland tropical rainforest at an altitude of 12–38 m above sea level, near the Agujas River, mostly at 1930–2200 hours. We counted all the snakes that we could see along the transect. Results: snake counts increase from August to September and then decline rapidly. The May snakes/rainfall peaks coincide, but the second snake peak occurs one month before the rain peak; we counted more snakes in dry nights, with the exception of Imantodes cenchoa which was equally common despite rain conditions. We saw less Leptodeira septentrionalis on bright nights, but all other species were unaffected. Along the six years, the number of species with each diet type remained relatively constant, but the number of individuals declined sharply for those that feed on amphibians and reptiles. We report Rhadinella godmani, a highland species, at 12–38 m of altitude. Conclusion: night field counts of snakes in Drake Bay, Costa Rica, show a strong decline from 2012 through 2017.

Powder and SLM additively manufactured parts of X5CrNiCuNb17-4 maraging steel were systematically investigated by electron microscopy to understand the relationship between the properties of the powder grains and the microstructure of the printed parts. We prove that satellites, irregularities and superficial oxidation of powder particles can be transformed into an advantage through the formation of nanoscale (AlMnSiTiCr)-oxides in the matrix during the printing process. The nano-oxides showed extensive stability in terms of size, spherical morphology, chemical composition and crystallographic disorder upon in situ heating up to 950°C in the scanning transmission electron microscope. Their presence thus indicates a potential for oxide-dispersive strengthening of this steel, which may be beneficial for creep resistance at elevated temperatures. The nucleation of copper clusters and their evolution into nanoparticles as well as the precipitation of Ni and Cr particles upon in situ heating have as well been systematically documented.

This work focuses on the study of the microstructure, hardening and stiffening effect caused by the secondary phases formed in titanium matrices. These secondary phases were originated from reactions between the matrix and boron particles added in the starting mixtures of the composites. Not only was the composite composition studied as an influencing factor in the behaviour of the composites, but also different operational temperatures. Three volume percentages of boron content were tested (0.9, 2.5 and 5 vol % of amorphous boron). The manufacturing process used to produce the composites was inductive hot pressing, which operational temperatures were between 1000 °C to 1300 °C. Specimens showed optimal densification. Moreover, microstructural study revealed the formation of TiB in various shapes and proportions. Mechanical testing confirmed that the secondary phases had a positive influence on the properties of the composites. In general, adding boron particles increased the hardness and stiffness of the composites; however rising temperatures resulted in greater increases in stiffness than in hardness.

The official recommendations to manage COVID-19 in the outpatient setting focus on high-cost drugs (remdesivir, nirmatrelvir-ritonavir, molnupiravir), suffering from many problems. Therefore, one may consider also other treatments meeting these criteria: • promising effectiveness, based on favorable randomized controlled trials (RCTs) of sufficient validity. Even without definitive evidence, physicians and informed patients can consider them if they are also: • safe, to the state of knowledge • with a very favorable opportunity cost • biologically plausible/not implausible • accessible • without major commercial sponsors in the trials promoting them, and with researchers without major conflicts of interests. The main focus is on a limited group of functional foods and some their active ingredients, with further mention of other substances of different origin, yet fully meeting all the aforementioned criteria. The functional foods and substances described and discussed certainly do not cover all the known effective therapies for COVID-19 (in one case also for Long-COVID), but the only therapies proposed in this paper currently satisfy all the above criteria. The supporting scientific evidence will favor meta-analyses of RCTs that include the most definitive outcome: all-cause mortality, i.e. the outcome that most fully informed people tend to prioritize. Furthermore, the reported evidence favors clinical studies of the most valid design, i.e. RCTs.

Listeria ivanovii and L. monocytogenes, are the only pathogenic species of the genus Listeria and share many virulence factors and mechanisms of pathogenicity. L. ivanovii shows host tropism towards small ruminants and rodents and much lower virulence for humans compared to L. monocytogenes. However, severe infections caused by L. ivanovii, resulting in bacteremia, abortion and stillbirth, occasionally occurred in immunocompromised persons and in pregnant women, while in immunocompetent hosts L. ivanovii can cause gastroenteritis. In this review the updated knowledge on virulence aspects and distribution of L. ivanovii in the environment and in food are summarized. Recent research on its virulence characters at genome level gave indications on how pathogenicity evolved in this bacterial species. As for L. monocytogenes, L. ivanovii infections occur after the ingestion of contaminated food, so an overview of reports regarding its distribution in the food products was carried out to obtain indications on the categories of foods exposed to contamination by L. ivanovii. It was found that a wide variety of food products can be a source of this microorganism and that, like L. monocytogenes, L. ivanovii is able to persist in the food production environment. Studies on its ability to grow in enrichment and isolation media suggested that its occurrence in nature might be underestimated. Moreover, virulence varies among strains for differences in virulence character regulation, presence/absence of genetic regions and the possible instability of a Listeria pathogenicity genomic island, LIPI-2, which is unique to L. ivanovii. We can conclude that L. ivanovii, as a possible pathogen for animals and humans, requires more focused investigations regarding its occurrence in the environment and in food and on intra-species variability of pathogenic potential.

People living in areas of significant seismic risk seldom undertake sufficient preparations to safeguard their family. This is most problematic in remote communities such as those along the Dead Sea Fault, Israel, where self-reliance is a key factor in coping with disasters. To facilitate individual and familial involvement in earthquake preparedness in remote areas, we designed a tool for self-assessment of risk and preparedness. The personalized risk assessment is based on national hazard and building standards, and on personal input regarding structure characteristics. The risk and preparedness evaluations enhance awareness and provide immediate feedback to help users improve familial preparedness. Spatial analysis of the data collected is used to form high-resolution maps that expose specific challenges for emergency response. A study conducted in the town of Mitzpe Ramon exposed neighborhoods with relatively high risk of damage and low preparedness. Integrating these results with seasonal stress-factors such as peak tourism and extreme weather, provides new and important insights on the ability of the local community and emergency forces to cope with multi-hazard situations. Analysis of the heterogeneous distribution of expected hardship within a community should be implemented world-wide to improve risk mitigation.

In this work we present a versatile, rapid, and low-cost manufacturing technique to develop bioceramic scaffolds that could enhance bone tissue regeneration via microwave preparation using a commercial microwave oven. The scaffolds were prepared combining hydroxyapatite and water glass (sodium trisilicate solution), foamed by using a microwaves oven and then characterized by means of SEM-EDS, mechanical properties, infrared spectroscopy (ATR-FTIR), density and stability test in water. Furthermore, in vitro tests were performed to verify the affinity of osteoclast cells versus the so prepared scaffold. The morphology of the samples showed interconnected pores suitable for promoting tissue regeneration and vascularization while specific mechanical properties were preserved. The physicochemical characterization and the in vitro tests presented promising results for bone regenerative applications.

The purpose of this article is to review a two year long implementation of an electronic health record (EHR) system at the outpatient department of a private hospital in Kathmandu, possibly a first implementation of its kind in Nepal. Procedures: The strategy designed for EHR implementation was based on Professor John P. Kotter's work on successful change management. Main findings: We found that keeping a close watch on the social dynamics affecting adoption decisions among users of the system was crucial for implementing the EHR; this was partly because the project received limited support from an erratically changing hospital leadership and lacked an EHR system suited to the needs of the users. Conclusions: The implementation described in this article is a good lesson on moving from control to drift in information systems implementation, and we hope this work will be useful to health IT professionals working in the space of digital transformation in resource-constrained environments.

Regional heterogeneity of microglia was first described a century ago by Pio del Rio Hortega. Currently, new hints on microglia heterogeneity across central nervous system (CNS) regions are still being unraveled by high-throughput techniques. It remains unclear whether these spatial specificities translate into different microglial behaviors in vitro. We cultured microglia isolated from the cortex and spinal cord and analyzed the effect of the CNS spatial source on in vitro behavior by applying the same experimental protocol and culture conditions. We analyzed microglial cell numbers, function, and morphology and found a distinctive in vitro phenotype. We found that microglia were present in higher numbers in spinal cord-derived glial cultures, presenting different expression of inflammatory genes and a lower phagocytosis rate under basal conditions or after activation with LPS and IFN-. Morphologically, cortical microglial cells are more complex and present longer ramifications, which were also observed in vivo in CX3CR1+/GFP transgenic reporter mice. Collectively, our data demonstrated that microglial behavior in vitro is defined according to specific spatial characteristics acquired in the tissue. Thus, our study highlights the importance of microglia as a source of CNS for in vitro studies.

Biomimetic foods are expected to have potential health benefits for the management and prevention of chronic diseases, such as diabetes and cardiovascular disease. In the current research, two commercially available and affordable plant proteins (soy protein isolate-SPI and pea protein isolate-PPI) at two levels (5%, 10%) were added to the Yangyu jiaotuan with an objective to develop a product with reduced glycemic properties and high protein content while maintaining its original taste and texture. The results showed that several important textural properties such as hardness and chewiness did not change significantly during the refrigerated storage. The storage modulus G′ increased with refrigerated storage time for different samples, there were significant differences among the five samples (with and without protein addition) with respect to frequency dependence during rheological measurements. The in vitro starch digestion experiments showed that the starch hydrolysis of Yangyu jiaotuan decreased considerably with the increase in PPI content and during refrigerated storage due to starch retrogradation. Protein has protected the microstructure and there was less damage when compared to samples without protein. The bimodal peaks of the particle size distribution curves showed that the newly developed Yangyu jiaotuan contains two different sizes of particles, the smaller particles (~30 μm) corresponded to PPI and starch granules, while the larger particles corresponded to the fragments of gel network of the starch matrix. Based on the above results, Yangyu jiaotuan mixed with pea protein is a convenient potato staple food product, which complies with the biomimetic potato food very well.

Starch is considered a major nutritional factor of maize (Zea mays L.) kernels, and can be influenced by the type of endosperm. The effects of endosperm type (vitreous and non-vitreous) and type of soil (clay and sand) on the starch content of kernels of maize, and on the in vitro degradation of starch were investigated in the rumen fluid after harvesting at 6 different maturity stages during 2008 and five different maturity stages in 2009. Starch degradation, in rumen fluid, was determined after 6 h, 12 h and 20 h of incubation, using the technique of gas production. A positive linear relationship was observed during gas production (ml gas/g organic matter) and starch degradation (g kg^-1 starch) at all incubation times, with starch contents of maize kernels to a certain limit of starch accumulation (i.e. at starch contents 451-519 g/kg OM) and negative relationship afterwards. This suggests significant effects of maturity on ruminal starch degradation of maize kernels. At each harvest date, ruminal starch degradation of maize kernels was affected by crop genotype as well as soil type. The in vitro ruminal degradation potential of starch in maize kernels was influenced by the nature of the endosperm, with a higher degradation of non-vitreous kernels than of vitreous kernels. The rumen starch degradation was also influenced by type of soil, with better degradation on clay than sandy soil. For all the incubation times and maturity stages the effects of genotype, soil type and maturity stage were consistent in rumen fluid.

Background. Increasing evidence demonstrate that concentration of protein in infant formula >1.9g/100Kcal with high levels of insulinogenic aminoacids is associated with accelerated weight gain, increased fat mass accumulation and risk of adiposity. Purpose of this study was to conduct a systematic review to determine the metabolic effects in infants feed with infant formula optimized in protein. Methods. Systematic review was conducted according PRISMA Statement. RCTs with one intervention group (infant formula with 1.6-1.9gr of protein/100Kcal) and at least one comparative control group (infant formula with >1.9gr of protein/100Kcal) were included. Standardized mean differences (SMD), through random model were calculated. Results. 15 RCT were included. Optimized protein in infant formula was associated with less gain of BMI at 24 months of follow-up (SMD -0.25, IC95% -0.36 to -0.13, p 0.01) and less fat mass accumulation (SMD -0.68, IC95% -0.98 to -0.37, p 0.01). Optimized protein was also associated to less gain of weight, weight/age Z-score, weight/length Z-score, BUN (mmol/dL) and IGF1 (ng/ml). No effect on length/age Z-score was observed. Conclusions. Robust evidence showed optimized protein (1.6gr/100Kcal to 1.9gr/100Kcal) in infant formula is associated with metabolic benefits in infants with less weight gain, BMI and fat mass accumulation.

This observational pilot study aimed to investigate continuous glucose monitoring (CGM) metrics in older Japanese patients with type 2 diabetes mellitus (T2DM) using a continuous glucose monitoring system (FreeStyle Libre Pro) for CGM during the first tirzepatide administration and compared the glycemic control measures before and after the treatment. The four patients re-ported a mean age of 79.5 years (standard deviation [SD]: 5.8), mean body mass index of 24.63 kg/m2 (SD: 4.7), and mean glycated hemoglobin level of 9.1% (SD: 2.1). After tirzepatide treatment, the mean of time in range, time above range, and time below range changed from 53.2% to 78.9% (p = 0.041), 45.8% to 19.7% (p = 0.038), and 1.0% to 1.5% (p = 0.206), respectively. Improved hy-perglycemia reduced the oral glucose medication in two cases and decreased the frequency of insulin injections in two cases. All cases demonstrated the CGM index improvement during short-term observation despite some differences. Future studies need to investigate the long-term impact on functional prognosis, safety, and tolerability, especially in nonobese older Asian pa-tients, to elucidate the potential benefits of tirzepatide. However, tirzepatide-associated robust glycemic improvement may simplify and reduce diabetes treatment-associated complication in older patients with T2DM.

It’s well known that existing horizontal well drilling and hydraulic fracturing technology that is used to achieve large-scale cost-effective production from immature to low-moderate maturity continental shale in China, where the organic matter mainly exists in the solid form is fairly ineffective. To overcome the obstacles, in-situ conversion technology seems feasible, while implementing it in the target layer along with estimating the amount of expected recoverable hydrocarbon in such shale formations seems difficult. This is because there is no guideline to choose the most appropriate method and select relevant key parameters for this purpose. Hence, based on thermal simulation experiments during the in-situ conversion of crude oil from the Triassic Chang 73 Formation in the Ordos Basin and the Cretaceous Nenjiang Formation in the Songliao Basin, this deficiency in knowledge was addressed. First, relationships between the in-situ converted total organic carbon (TOC) content and the vitrinite reflectance (Ro) of the shales and between the residual oil volume and the hydrocarbon yield was established. Second, the yields of residual oil and in-situ converted hydrocarbon were measured, revealing their sensitivity to fluid pressure and crude oil density. In addition, a model was proposed to estimate the amount of in-situ converted hydrocarbon based on the TOC, hydrocarbon generation potential, Ro, residual oil volume, fluid pressure, and crude oil density. Finally, a method was established to determine key parameters on the final hydrocarbon yield from immature to low-moderate maturity organic material during in-situ conversion in shales. Following the procedure outlined in this paper, estimated recoverable in-situ converted oil in the shales of the Nenjiang Formation in the Songliao Basin was estimated to be approximately 292×108 tons, along with 18.5×1012 cubic meters of natural gas, in an area of approximately 8×104 square kilometers. Collectively, the method developed in this study is independent from the organic matter type and other geological and/or petrophysical properties of the formation and can be applied to other areas globally where there isn’t any available in-situ conversion thermal simulation experimental data.

Malignant melanoma is one of the most aggressive and resistant tumor types which is often accompanied by poor prognosis when spread to nearby or distant tissues. Even though an increasing number of second-line therapies are available for cancer patients, the 5-year survival rate of melanoma patients with regional and distant metastases is still rather low. Therefore, there is an urgent need to develop new, highly efficient treatments. Melanocortin-1-receptor (MC1R) is a cell surface receptor for α-MSH. It is responsible for melanogenesis and is shown to be overexpressed on the surface of cancer cells in a subset of melanoma patients. Here, we designed and synthesized α-MSH analogs and conjugated them to daunomycin through oxime linkage. Using our peptide-drug conjugates (Dau-α-MSHs), we performed comparative in vitro and in vivo evaluations to reveal their suitability for tumor targeting. Firstly, the expression level of MC1R was determined in various melanoma cell lines via RT-qPCR. Then, we examined the antiproliferative effect of our Dau-α-MSHs, moreover we determined the cellular uptake profile and intracellular localization of Dau-α-MSHs. The most efficient Dau-α-MSHs were investigated in vivo using a murine xenograft melanoma model. We found that various cell lines show differential expression on the mRNA levels. We also showed that healthy primary cells have lower expression of MC1R compared to tumor cell lines. Moreover, the concentration-dependent cellular uptake profile of Dau-α-MSHs was detected and the compounds exhibited a great antiproliferative effect on melanoma cell lines. We also provided evidence that our novel Dau-α-MSHs can inhibit tumor expansion significantly and are suitable for targeted tumor therapy.

Biofouling is the unwanted adsorption of cells, proteins, or intracellular and extracellular bio-molecules that can spontaneously occur on the surface of metal nanocomplexes. It represents a major issue in bioinorganic chemistry because it leads to the creation of a protein corona, which can destabilize a colloidal solution and result in undesired macrophage-driven clearance, consequently causing failed delivery of a targeted drug-cargo. Hyaluronic acid (HA) is a bioactive, natural mucopolysaccharide with excellent antifouling properties, arising from its hydrophilic and polyanionic characteristics in physiological environments which prevent opsonization. In this study, hyaluronate-thiol (HA-SH) (MW 10 kDa) was used to surface-passivate gold nanoparticles (GNPs) synthesized using a citrate reduction method. HA functionalized GNP complexes (HA-GNPs) were characterized using absorption spectroscopy, scanning electron microscopy, zeta potential, and dynamic light scattering. GNP cellular uptake and potential dose-dependent cytotoxic effects due to treatment were evaluated in vitro in HeLa cells using ICP-OES and Trypan blue and MTT assays. Further, we quantified the in vivo biodistribution of intratumorally injected HA functionalized GNPs in Lewis Lung carcinoma (LLC) solid tumors grown on the flank of C57BL/6 mice and compared localization and retention with nascent particles. Our results reveal that HA-GNPs show overall greater peritumoral distribution (**p<0.005, 3 days post-intratumoral injection) than citrate-GNPs with reduced biodistribution in off-target organs. This property represents an advantageous step forward in localized delivery of metal nano-complexes to the infiltrative region of a tumor, which may improve the application of nanomedicine in the diagnosis and treatment of cancer.

Soy isoflavones are considered important sources of bioactive compounds, but they are poorly absorbable, due to their large hydrophilic structures. Some biotransformation strategies have been used to convert the glycosidic form into aglycones, making them available for absorption. This study evaluated the potential of enzymatic and/or microbial fermentation bioprocesses in soymilk extract before and after gastrointestinal in vitro digestion. Commercial β-glucosidase and mix of commercial probiotics containing Lactobacillus acidophilus, L. casei, Lactococcus lactis, Bifidobacterium bifidum e B. lactis were used to biotransform soymilk extract. Isoflavone profile was quantified by HPLC-DAD, total phenolic content by Folin–Ciocalteu test, and antioxidant capacity by ORAC and FRAP. Soymilk enzymatically treated (ET) followed by microbial fermentation (ET+F) resulted in the conversion of glycosylated isoflavones (6-fold lower than control for daidzin and 2-fold for genistin) to aglycones (18-fold greater than control for dadzein and genistein), besides to increase the total phenolic content (3.48 for control and 4.48 mg/ml ET+F) and to improve antioxidant capacity represented by the ORAC (120 for control and 151 mg/ml ET+F) and by the FRAP (285 for control and 317 µl/ml for ET+F) before in vitro digestion. Further, the digested ET+F samples resulted a higher content of genistein (2-fold higher than control) also an increase in the total phenolic content (2.81 for control and 4.03 mg/ml for ET+F) and antioxidant capacity by ORAC were greater compared to undigested samples. In addition, the microbial fermentation process isolated also resulted in the positive effects, but de combination of ET followed by F presented a synergistic effect, suggesting the greater potential for both bioprocesses to contribute to functional and nutritional properties on fermented soy-based products.

Sechium compositum (Cucurbitaceae) is a wild species that is distributed in the Soconusco region, Chiapas, Mexico, and the border with Guatemala. This species has an intangible biochemical value resulting from the pharmacological relevance of its secondary metabolites. However, as a consequence of the lack of knowledge about its importance, it is being displaced from its habitat at an accelerated rate, incurring the risk of genetic loss. Therefore, an in vitro culture protocol with two experimental phases was evaluated to propagate, conserve, and regenerate this species. The first phases considered the multiplication of seedlings, adding seven concentrations (0.1, 0.2, 0.4, 0.6, 0.8, 1.0, 1.2 mg mL-1) of 6-benzylaminopurine (BA) and thidiazuron (TDZ) and evaluating the number of buds, shoots, and seedling height. The best multiplication response was recorded with 0.1, 0.2, 0.4, and 1.0 mg L-1 of BA and 0.1 mg L-1 of TDZ, as well as the MS base culture medium. With 0.1 mg L-1 of BA, 52-mm height, 1.36 shoots, and 9.22 buds were obtained, surpassing the MS control (MS culture medium alone); likewise, twice more roots (80%) and a 14% reduction in the bud structure were packed in 50 repetitions. The second phase consisted of inducing callus formation from stem and leaf explants through the addition of 0.5, 1.0, and 2.0 mg L-1 of TDZ and 2,4-Dichlorophenoxyacetic acid (2,4-D) to the medium. The results demonstrated that the induction of callogenesis in S. compositum has a better start from the stem in a medium with 2.0 mg L-1 of 2,4-D, whose value was 4.89 —equivalent to 97.8% callus formation around the explant. The addition of 500 mg L-1 of polyvinylpyrrolidone (PVP) is also suggested to reduce oxidation. This protocol represents a significant advance in the conservation, multiplication, and callogenesis of S. compositum and contributes to its rescue and revaluation in the face of the danger of extinction.

Although, Artificial intelligence (AI) helps experts with crime analysis, research, and understanding, it has a favourable influence on cyber security. It strengthens the tools that businesses use to safeguard their networks, clients, and workers against dangerous online behaviour. However, artificial intelligence is infamous for requiring a lot of resources. It may not, however, always be relevant. Additionally, it can provide hackers a new tool and advance their abilities. Actually, the VPN industry benefits from AI in the same way. The threat posed by machine learning in AI to user data privacy may be lessened by using a VPN on all of your devices. Because they use machine learning algorithms, VPNs are better equipped to shield their users from internet-based threats. Artificial intelligence (AI) has reportedly being investigated as a means of enhancing internet security for a considerable amount of time, according to Smart Data Collective. We anticipated that AI and machine learning will have a substantial impact on the future of cyber security around two years ago.

In this letter we investigate if SARS-CoV-2 RNA is involved in the increased ageing of alveolar cells. Our in silico study is explorative. With the results we are able to outline experiments with AEC2 repair of bleomycin damaged alveolar cells. If AEC2 repair capability is diminished by spike RNA then perhaps this result provides a first step on a route to treat immortal lung cancer cells.

The present state of research in Computational Fluid Dynamics (CFD) is marked by an ongoing process of refining numerical methods and algorithms with the goal of achieving accurate modeling and analysis of fluid flow and heat transfer phenomena. Remarkable progress has been achieved in the domains of turbulence modeling, parallel computing, and mesh generation, resulting in heightened simulation precision when it comes to capturing complex flow behaviors. Nevertheless CFD faces a significant challenge due to the time and expertise needed for meticulous simulation setup and intricate numerical techniques. To surmount this challenge, we introduce paint2sim—an innovative mobile application designed to enable on-the-fly 2D fluid simulations using a device’s camera. Seamlessly integrated with OpenLB, a high-performance Lattice Boltzmann-based library, paint2sim offers accurate simulations. The application leverages the capabilities of the Lattice Boltzmann Method (LBM) to model fluid behaviors accurately. Through a symbiotic interaction with the open-source OpenCV library, paint2sim can scan and extract hand-drawn simulation domains, affording the capability for instant simulation and visualization. Notably, paint2sim can also be regarded as a digital twin, facilitating just-in-time representation and analysis of 2D fluid systems. The implications of this technology extend significantly to both fluid dynamics education and industrial applications, effectively lowering barriers and rendering fluid simulations more accessible. Encouragingly, the outcomes of simulations conducted with paint2sim showcase promising qualitative and quantitative results. Overall, paint2sim offers a groundbreaking approach to mobile 2D fluid simulations, providing users with just-in-time visualization and accurate results, while simultaneously serving as a digital twin for fluid systems.

Groundwater contamination is an ever-growing environmental issue that has attracted much and undiminished attention for the past half century. Groundwater contamination may originate from both anthropogenic (e.g., hydrocarbons) and natural compounds (e.g., nitrate and arsenic); to tackle the removal of these contaminants, different technologies have been developed and implemented. Recently, bioelectrochemical systems (BES) have emerged as a potential treatment for groundwater contamination, with reported in situ applications that showed promising results. Nitrate and hydrocarbons (toluene, phenanthrene, benzene, BTEX and light PAHs) have been successfully removed, due to the interaction of microbial metabolism with poised electrodes, in addition to physical migration due to the electric field generated in a BES. The selection of proper BESs relies on several factors and problems, such as the complexity of groundwater and subsoil environment, scale-up issues, and energy requirements that need to be accounted for. Modeling efforts could help predict case scenarios and select a proper design and approach, while BES-based biosensing could help monitoring remediation processes. In this review, we critically analyze in situ BES applications for groundwater remediation, focusing in particular on different proposed setups, and we identify and discuss the existing research gaps in the field.

This paper provides a review of an emerging field in the food processing sector, referring to efficient and safe food supply chains, ’from farm to fork’, as enabled by Artificial Intelligence (AI). Recent advances in machine and deep learning are used for effective food production, energy management and food labeling. Appropriate deep neural architectures are adopted and used for this purpose, including Fully Convolutional Networks, Long Short-Term Memories and Recurrent Neural Networks, Auto-Encoders and Attention mechanisms, Latent Variable extraction and clustering, as well as Domain Adaptation. Three experimental studies are presented, illustrating the ability of these AI methodologies to produce state-of-the-art performance in the whole food supply chain. In particular, these concern: (i) predicting plant growth and tomato yield in greenhouses, thus matching food production to market needs and reducing food waste or food unavailability; (ii) optimizing energy consumption across large networks of food retail refrigeration systems, through optimal selection of systems that can get shut-down and through prediction of the respective food de-freezing times, during peaks of power demand load; (iii) optical recognition and verification of food consumption expiry date in automatic inspection of retail packaged food, thus ensuring safety of food and people’s health.

We present a high-throughput nanoindentation study of in-situ bending effects on incipient plastic deformation behavior of polycrystalline and single-crystalline pure aluminum and pure copper at ultra-nano depths (<200nm). We find that hardness displays a statistically inverse dependence on in-plane stress for indentation depths smaller than 10nm, and the dependence disappears for larger indentation depths. In addition, plastic noise in the nanoindentation force and displacement displays statistically robust noise features, independently of applied stresses. Our experimental results suggest the existence of a regime in FCC crystals where ultra-nano hardness is sensitive to residual applied stresses, but plasticity pop-in noise is insensitive to it.

Capturing atmospheric CO2 and storing it in natural rock systems (i.e., alkaline earth silicate and hydroxide minerals) through carbonation reactions is a promising greenhouse gas mitigation research, and largely depends on the use of hydrated ultramafic rocks (serpentinites), which are widespread in orogenic belts around the globe. The Jurassic ophiolites in the Southern Apennines represent a natural analogue and a great opportunity for the mineralogical sequestration of CO2. Serpentinites of the Pollino ophiolite Massif have been widely studied for their mineralogical, petrographic, and chemical characteristics, providing major findings on their impact on environmental and human health issues. Serpentinites here have been divided into cataclastic and massive types based on their structures and are characterized by pseudomorphic and vein textures. The mineralogy of the studied serpentinites consists of lizardite, antigorite, clino-crysotile, Cr-chlorite, magnetite, tremolite, actinolite, pyroxene and calcite, and the most commonly occurring serpentine minerals are polymorphs of serpentine including lizardite, clino-crysotile and antigorite. Systematic petrographic and mineralogical studies of serpentinites in ophiolites, such as those outcropping in the Southern Apennines can represent a starting point for the study of natural materials, which can be used for CO2 storage and sequestration. A particular attention must be given to those carbonate phases, produced by carbonation processes to check whether the serpentinites of the Pollino Massif can be used for the induced mineral Carbon Capture Storage (CCS). If successful, this technique and the Pollino Massif serpentinites can become highly significant in safeguarding the health of our planet's climate.

This study investigated how positive (e.g., incentives) and negative (e.g., restrictions) reinforcement used in vaccination promotional messages and trust in government impact parental vaccine perceptions and decisions on vaccinating their children during a large-scale infectious disease crisis. Two hundred and eighty-six parents of unvaccinated teens participated in a 2 (reinforcement: positive vs. negative) × 2 (trust in government: high vs. low) between-subjects experimental survey. Positive reinforcement (e.g., gift cards for the vaccinated) was more effective for parents with low trust in the government to improve their attitudes and intentions toward child vaccination, while parents with high trust in the government were unaffected by reinforcement types. To the best of our knowledge, this study is among the first to examine the effects of both positive and negative reinforcement on vaccination perceptions and behavioral intentions through a controlled experiment and is the first study to do so in a large-scale infectious disease crisis setting. This research is expected to help public health professionals better prepare for and manage virus-induced public health crises in the future.

In-situ observation on the austenite grain growth and martensite transformation in a developed NM500 wear-resistant steel were conducted on a Confocal Laser Scanning High-temperature Microscope (CSLM). Results indicated that the martensite nucleation did not synchronously proceed during quenching process. The selective prenucleation dominated in martensite nucleation, which dividing untransformed austenite into several regions, and resulting in the larger size of fresh martensite. Martensite can not only nucleate at parent austenite grain boundaries, but also nucleate in the preformed martensite laths and twins. Smaller constraint in the martensite growth was achieved in a larger parent austenite grain size, leading to the longer fresh martensite and secondary martensite. Besides, the transformation kinetics of martensite was accelerated in a higher quenching temperature. Moreover, the martensitic laths presented in parallel laths (0~2°) based on the pre-formed lath or distributed in triangle, parallelogram or hexagon with an angle of 60° or 120°. Interestingly, martensitic lath also traversed the unstable new parent austenitic grain boundaries. In addition, the size of austenite grains increased with the quenching temperature, and austenite grains coarsened in a short time at a higher quenching temperature of 1160 ℃. Furthermore, a large amount fine dispersed particles redissolved and ripped at 1160 ℃, resulting in the many large and visible carbonitrides.

The absorption of medium-chain fatty acids (MCFA) depends on the solubility of these components in the gastric fluid. Parameters such as the total MCFA concentration, carboxyl ionization level, and carbon chain length affect the solubility of these molecules. Moreover, the enzymatic lipolysis of solubilized triacylglycerol (TAG) molecules may depend on the carbon chain length of the fatty acids (FAs) components and their positions on the glycerol backbone. This present study aimed at investigating the effect of electrolyte usually formed during the gastric digestion phase on the solubility of MCFA, and evaluating the influence of the FA carbon chain length on the lipolysis rate during the in vitro digestion simulation. The results obtained here showed that the increasing of electrolyte concentrations tend to decrease the mutual solubility of systems composed by the caproic and caprylic fatty acids + sodium chloride, sodium bicarbonate, and potassium chloride solutions. We also observed that a conventional version of the thermodynamic UNIQUAC model was able to correlate the liquid-liquid phase behavior of the electrolyte solutions. Regarding the in vitro digestion simulation, the experimental data indicated that the action of the pancreatic enzyme occurred preferentially in TAG molecules comprised of short and medium-chain fatty acids.

Abstract: This article aims to better understand the mechanisms that connect climate change perceptions and general willingness to engage in pro-environmental behavior using Spanish cross-sectional data (N = 403). To do this, we first developed and validated the General Willingness for Environmental Behavior Scale (GWEBS), which includes the classical approach of voluntarily doing new actions but also actions implying not doing things (degrowth) and actions forced by social constraints. The exploratory and confirmatory factor analysis showed a good fit for the one-factor structure, which had adequate validity based on their relationship with other variables. Additionally, the GWEBS distinguished between women and men, left- and right-oriented people, and people who belonged to pro-environmental groups and people who did not. In the second place, we tested the parallel mediator role of eco-anxiety and trust in science in the relationship between climate change perceptions and the GWEBS. The results showed that eco-anxiety, fully, and trust in science partially mediated such a relationship, making them crucial to mobilize the intention to act following the perception. This study contributes to our understanding of the psychological mechanisms that eventually drive pro-environmental behaviors and provides a clear direction for future research.

The research aims to discover the natural occurrence of patulin (PAT) in selected citrus fruits from the central cities of Punjab and Pakistan's Northern cities. Total 2970 samples of twelve citrus fruits; kinnow, orange, grapefruits, bitter orange, mausami, red blood, pineapple, sweet orange, rough lime, sweet lime, kagzi lime and lemon were examined using liquid chromatography fitted with UV detector. The limit of detection (LOD) and quantification limit was 0.04 and 0.12 µg/kg, respectively. The results have shown that 56% of samples of citrus fruits from Punjab's central cities, Pakistan, were discovered to be infected from PAT. The elevated amounts of PAT ranging from 0.04 to 1150 µg/kg were found in citrus fruit samples from Multan cities. Furthermore, 31.7% of samples of citrus fruits from Northern cities of Pakistan were discovered to be infected with PAT, and the elevated amounts were found ranging from 0.04-320 µg/kg from Swat city. About 22.1% of samples of citrus fruits have levels of PAT greater than the suggested limits established by the European Union (EU). PAT's dietary intake levels ranged from 0.10-1.11 µg/kg bw/day from the central cities of Punjab, Pakistan, and 0.13-1.93 µg/kg bw/day were documented from Northern cities of Pakistan.

The research aims to discover the natural occurrence of patulin (PAT) in selected citrus fruits from the central cities of Punjab and Pakistan's Northern cities. Total 2970 samples of twelve citrus fruits; kinnow, orange, grapefruits, bitter orange, mausami, red blood, pineapple, sweet orange, rough lime, sweet lime, kagzi lime and lemon were examined using liquid chromatography fitted with UV detector. The limit of detection (LOD) and quantification limit was 0.04 and 0.12 µg/kg, respectively. The results have shown that 56% of samples of citrus fruits from Punjab's central cities, Pakistan, were discovered to be infected from PAT. The elevated amounts of PAT ranging from 0.04 to 1150 µg/kg were found in citrus fruit samples from Multan cities. Furthermore, 31.7% of samples of citrus fruits from Northern cities of Pakistan were discovered to be infected with PAT, and the elevated amounts were found ranging from 0.04-320 µg/kg from Swat city. About 22.1% of samples of citrus fruits have levels of PAT greater than the suggested limits established by the European Union (EU). PAT's dietary intake levels ranged from 0.10-1.11 µg/kg bw/day from the central cities of Punjab, Pakistan, and 0.13-1.93 µg/kg bw/day were documented from Northern cities of Pakistan

A typical orchard's mechanical operation consists of three or four stages: lining, digging for plantation, moving the seedling from nurseries to the farm, moving the seedling to the planting hole, and planting the seedling in the hole. However, the digging the planting hole is the most time-consuming operation. In fruit orchards, robots' usage is increasingly becoming more prevalent to increase operational efficiency. They offer practical and effective services to both industry and people, whether they are assigned to plant trees, reduce the use of chemical fertilizers, or carry heavy loads to relieve staff. Robots can operate for extended periods of time and can highly adept at repetitive tasks like planting many trees. The present study aims to identify the locations for planting trees in orchards using geographic information systems (GIS), to develop an autonomous drilling machine and use the developed robot to open planting holes. The agricultural mobile robot is a four wheeled nonholonomic robot with differential steering and forwarding capability to stable target positions. The drilling system, which is a y-axis shifter driven by a DC motor with reducer includes an auger with a 2.1 HP gasoline engine. SOLIDWORKS software was used for designing and drawing of the mobile robot and drilling system. The Microsoft Visual Basic.NET programming language was used to create the robot navigation system and drilling mechanism software. The cross-track error (XTE), which determines the distances between the actual and desired holes positions, was utilized to analyze the steering accuracy of the mobile robot to the drilling spots. Consequently, the average of the arithmetic means was determined to be 4.35 cm, and the standard deviation was 1.73 cm. This figure indicates that the suggested system is effective for drilling plant holes in orchards.

Type 2 diabetes mellitus (T2DM) accounts for one-sixth of deaths, globally, whereas cancer is the second leading cause of death in the U.S. T2DM is a known risk factor for many cancers. This review examines the link of Reactive oxygen Species (ROS)-altered metabolic and signaling pathways in T2DM to cancer. These reprogrammed metabolic and signaling pathways are activated that contribute to diabetic complications, impact redox balance (Oxidative Stress), and have differential roles in early and late stages of cancer. If the respiratory chain is highly reduced (as under hyperglycemic conditions) or if reduced cofactors accumulate, ROS are greatly elevated. ROS may cause mutations in mitochondrial DNA (mtDNA) that result in further ROS elevation. Amplification of ROS results in activation of PKC, an overarching signaling pathway that activates MAPK with subsequent regulation of several factors that result in pathophysiological manifestations of T2DM and cancer. Upregulation of PKC leads to deregulation of NF-kß that regulates the PKB/P13/Akt pathway that orchestrates cell survival, growth, proliferation, and glucose metabolism manifested in cancer. It also affects Insulin Receptor Substrate (IRS-1), decreasing insulin stimulated glucose transport and glucose uptake, disrupting subsequent cell signaling pathways contributing to the development of T2DM. Dyslipidemia is a hallmark of T2DM and cancer. ROS-induced lipid peroxidation leads to systemic inflammation, producing inflammatory prostaglandins, cytokines and chemokines that result in tumor proliferation, rapid tumor growth, and modulation of immunity. The dual role of ROS in early and late stages of cancer make antioxidant therapy precarious and may be responsible for controversial results. A system that delivers an antioxidant directly to mitochondria may be useful in inhibiting formation of ROS early during the pre-diabetic stage whereas antioxidant therapy must be halted in later stages to retard metastasis.

Vitamin D3 deficiency is a global phenomenon, which can be coped with supplementation and food fortification. However, vitamin D3 bioaccessibility may depend on factors, such as matrix composition and interactions throughout the gastrointestinal tract. This research focused on the effect of different matrices on vitamin D3 content during digestion, and the effect of pH on its bioaccessibility. The INFOGEST protocol was employed to simulate digestion. Three different types of commercial supplements, two foods naturally rich in vitamin D3, and three fortified foods were investigated. High-Performance Liquid Chromatography was used to determine the vitamin D3 initial content in supplements and foods, as well as after each digestion stage. Results indicated that foods exhibited higher bioaccessibility indices compared to supplements, and a higher percentage retention at the end of the gastric phase. The pH study revealed a positive correlation between increased gastric pH and the corresponding content of vitamin D3. Interestingly, exposing the matrix to low pH during the gastric phase resulted in an increased intestinal content of D3. Vitamin D3 is more bioaccessible from foods than supplements, and its bioaccessibility is susceptible to changes in gastric pH. Fasting conditions (i.e. gastric pH=1) enhances vitamin’s bioaccessibility.

Blended learning, the integration of online and face-to-face instruction, has garnered attention in education. This paper aims to explore challenges in blended learning faced by students, teachers, and parents and propose mitigating strategies. The study employed qualitative research methods and involved 30 participants from St. Michael's College. Findings revealed primary challenges, including technical difficulties, time management, lack of interaction, and varying digital literacy levels. These challenges influenced engagement, communication, and student achievement. The study utilized a theoretical framework encompassing Technological Pedagogical Content Knowledge, Social Presence Theory, and Activity Theory. Strategies recommended comprise providing technical support, promoting communication and collaboration, offering professional development, and leveraging learning analytics. The study contributes to the existing literature by identifying specific challenges and proposing practical recommendations for enhancing blended learning effectiveness. Limitations include a small sample size and context-specific findings. Future research should investigate these challenges in broader settings and examine the long-term effects of the recommended strategies. Addressing blended learning challenges can empower educators, administrators, and policymakers to create supportive and effective learning environments for all stakeholders involved.

Dietary guidance to recommend food patterns to deliver nutrients has been well accepted for the past century. Foods to deliver essential nutrients and energy are needed across the life cycle and are dependent upon local industries and accepted cultural practices to deliver essential nutrients to prevent nutrient deficiency diseases. Since the 1980s, dietary guidelines to prevent chronic diseases have relied on epidemiological research to predict what dietary patterns are linked to reduced risk of chronic disease or links to health outcomes. Dietary guidelines have been broad, typically recommending avoiding “too much sugar”, “too much saturated fat”, and “too much sodium”. Efforts to fine tune these recommendations have met with limited scientific data to support more specific recommendations across the life cycle. Consumers have become skeptical of dietary guidelines as media coverage of new studies is often in conflict with accepted nutrition dogma. We discuss whether we really have a science-based databank to support dietary guidelines, based on a scientific session at the 10th International Conference on Nutrition and Growth.

This study aimed to analyze areas of concern and support of the Austrian general population two years into the COVID-19 pandemic. A representative sample (N = 1,031) of the Austrian general population was surveyed online between April 19 and 26, 2022. A qualitative study design was used to explore the factors of most considerable current concern (question 1) and the most important sources of support (question 2). The responses to the two open-ended questions were evaluated using conventional content analysis and categories were formed according to the frequency of the answers. The analysis revealed that inflation and finances (30% of participants) and the war in Ukraine (22%) were the greatest sources of concern, followed by mental health (10%), and physical health (10%). Factors such as social contacts within and outside the family were mentioned most frequently as sources of support (36% of participants), followed by recreational activities (23%) and attitudes and abilities (22%). Compared to data collected at the end of the first year of the pandemic (between December 23, 2020, and January 4, 2021), concerns about one's financial situation was now mentioned more frequently (30,4% vs. 8,5%). On the other hand, different types of pandemic-related concerns were less often mentioned. Social contacts and recreation were mentioned as the most important sources of support at both time points (46% and 36% of the participants). Results suggest that the economic concerns are lagging behind the restrictions imposed by the pandemic. In addition, the impending war in Ukraine seems to have a relevant impact on mental health in Austria. Further nuanced qualitative research, particularly involving vulnerable groups like low-income individuals and the unemployed, is crucial.

Different dopamine receptor (DR) subtypes are involved in pathophysiological conditions such as Parkinson´s Disease (PD), schizophrenia and depression. While many DR-targeting drugs have been approved by the FDA, only a very small number is truly selective for one of the DR subtypes. Additionally, most of them show promiscuous activity at related G-protein coupled receptors, thus suffering from diverse side-effect profiles. Multiple studies have shown that combined in silico / in vitro approaches are a valuable contribution to drug discovery processes. They can also be applied to divulge the mechanisms behind ligand selectivity. In this study, novel DR ligands were investigated in vitro to assess binding affinities at different DR subtypes. Thus, nine D2R/D3R-selective ligands (micro- to nanomolar binding affinities, D3R-selective profile) were successfully identified. The most promising ligand exerted nanomolar D3R activity (KI = 2.3 nM) with 263.7-fold D2R/D3R selectivity. Subsequently, ligand selectivity was rationalized in silico based on ligand interaction with a secondary binding pocket, supporting selectivity data determined in vitro. The developed workflow and identified ligands could aid in the further understanding of structural motifs responsible for DR subtype selectivity, thus, benefitting drug development in D2R/D3R-associated pathologies like PD.

The use of antibiotics in neonatal units worldwide varies significantly. We included data from 2015-2022 from the EpicLatino database, which comprises a network of 32 units in Latin America and the Caribbean with gestational age at birth (GA) of ≤ 32 weeks. A questionnaire was sent to the EpicLatino units, to correlate practice with outcomes. Negative binomial regression with standard errors and confidence intervals computed for incidence-rate ratios (IRRs) was used for comparative statistics on antibiotic days per 1000 patient-days between units. All units that responded had 1-6 differences with the reference unit (Unit 2) with the best results, but there was no clear association with the IRR. Each EpicLatino unit should review its statistics to explore possibilities for reducing antibiotic usage.

This study aimed to extract bioactive compounds from apple (Malus domestica) peel waste using supercritical CO2 extraction. The bioactive fractions from apple peels from the three Italian cultivars were extracted applying a temperature of 60 °C and a pressure of 250 bar for 15 min. 20% ethanol was used as a co-solvent. The extraction process was carried out at a flow rate of 2 mL/min and their total polyphenol (TP), anthocyanin (TA), ascorbic acid (AA), and antioxidant activity contents (TAC) were measured. The extracts from the Stark cultivar had the highest levels of polyphenols, anthocyanins, and ascorbic acid, while the Royal Gala cultivar had the highest total antioxidant activity. Chromatographic analyses were also performed to characterize polyphenols. The extracts were then tested for their effect on the mitochondrial NADH-ubiquinone oxidoreductase (Complex I) activity on mitochondria isolated from human embryonic kidney cells (HEK239) cells, with the Stark extracts showing the most positive response in terms of NADH oxidation. These findings highlight the potential of apple peel waste as a source of functional phytocompounds and suggest the Stark cultivar extracts may have pharmacological applications. This study supports the circular bioeconomy by promoting the use of waste products as a valuable resource.

Finding new, safe strategies to prevent and control rheumatoid arthritis is an urgent task. Of particular interest in this regard are bioactive peptides and peptide-rich protein hydrolyzates, which represent a new trend in the development of functional foods and nutraceuticals. The resulting tissue hydrolyzate of the chicken embryo (CETH) has been evaluated for acute toxicity and tested against chronic arthritis induced by Freund's full adjuvant in rats. The anti-arthritic effect of CETH was studied on the 28th day of the experiment after two weeks of oral administration of CETH at doses of 60 and 120 mg/kg body weight. Arthritis was evaluated on the last day of the experiment on the injected animal paw using X-ray computerized microtomography and histopathology analysis methods. The CETH effect was compared with the non-steroidal anti-inflammatory drug diclofenac sodium (5 mg/kg). Oral administration of CETH was accompanied by effective dose-dependent correction of morphological changes caused by the adjuvant injection. CETH had relatively high recovery effects in terms of parameters for reducing inflammatory edema, inhibition of osteolysis, prevention of osteophitosis, reduction of the inflammatory reaction of periarticular tissues, and cartilage degeneration. This study presents a potential theoretical strategy for the safe correction of this pathological process and, for the first time, shows that CETH may be a powerful potential nutraceutical agent or bioactive component of functional products in the treatment of rheumatoid arthritis.

The classical propositional calculus (zero-order logic, classical propositional logic), is the most fundamental two-valued logical system. In this paper we present a proof of inconsistency of the classical propositional calculus. Then, we get right away the conclusion that the metatheory of the classical propositional calculus is inconsistent.