This article objective was to identify a centenary trend in the growth and development of girls in the metropolis of Moscow. Material and methods — The physical development (body length and weight, chest circumference, right hand muscle strength, and menstrual function development) of Moscow girls was studied during the period from 1920 to 2020. The amount of own observations was 4581 girls aged 8-17 years. Results – A comparative analysis of the physical development of Moscow school girls of different decades revealed a statistically significant increase in body length by 3-5 cm and a significant increase in chest circumference in all age groups of girls of the beginning of the XXI century, compared with their peers in the 1960s and 1980s, which indicates the completion of the gracialization processes that have been observed since the 1980s. However, in all age groups, a decrease in the muscle strength of the right hand is still being noticed. Earlier terms of menarshe onset in modern Moscow school girls (12 years 9 months) and a shift in growth jumps to earlier terms were established. It is shown that the age of menstruation depends on the level of family wealth. Conclusions. In Moscow girls in the centenary dynamics, a tendency to increase the total body size and shift the terms of biological maturation to earlier terms was revealed.

Grape pomace (GP) is a winemaking residue that can be used as a functional ingredient due to its phenolic content, among others. The influence of GP, grape pomace extract (GPE) and encapsulated grape pomace extract (BGPE) on the phenolic compounds content, physical, textural and sensory properties of the functional biscuit (FB) was studied. In the production of FB, 10-30 % of the wheat flour in the standard biscuit was replaced by GP or by adding GPE and BGPE in amounts equivalent to the phenolic content of GP. The highest content of phenolic compounds was found when 30 % of GP was used. The antioxidant activity (AA) correlated well with the phenolic compound content (R > 0.87). The antiproliferative activity of biscuit extracts against cancer cell lines is in the following order: SW620 > Caco-2 > Hep G2, but the positive correlation with phenols and AA was not found. Textural properties of biscuits with GPE and BGPE addition were worse compared to GP and standard biscuits, i.e. they were harder. Biscuits with BGPE addition received the highest overall sensory score. The results indicate that biscuits enriched with phenolics from grape pomace could be a promising functional food with good sensory properties.

Asymmetry plays a major role in biology at all scales. This can be seen examining the helix of DNA, the fact that the human heart is on the left side, or that most people use their right hand. A single protein such as Myosin 1D can induce helical motion in another molecule. This causes cells, organs, and even entire bodies to twist in a domino effect, causing left-right behaviour. More in general, athlete movements are often asymmetric and, during the physical rehabilita-tion after injury the asymmetry is visually discernible. Herein we review the molecular basis of movement asymmetries and report on the available knowledge on the few therapeutics inves-tigated so far such as meloxicam. From a more rehabilitative perspective, it is very important to use effective methods to control the process of resolving the injury-related movement asym-metry through the complex use of specialized exercises, measurements and gait analysis which all can provide useful information on the effectiveness of rehabilitation plans. If for each athlete the normal range of asymmetry is known, the asymmetry can be treated individually and the evolution can be monitored over time. Appropriate measures should be taken if the movement asymmetry is outside this range. In addition, genetic, physiological, and psychological factors relevant to athlete health should be considered in the process of assessing and improving exer-cise asymmetry as we also discuss in this review. The main proposal of this work is that move-ment asymmetries in athletes should be treated individually, taking into account the athlete’s genetics, physical condition, and previous injuries.

Several lime mortars for the repair of painted plasters of the rock cut church of Ss. Pietro and Paolo in Matera were studied. They were designed taking into account both aesthetic criteria that need to be fulfilled in the field of paintings restoration, and physical-mechanical compatibility with the original materials on site, i.e. the pre-existing plasters and the supporting rock. Mixes with calcareous and silica aggregates, based on different grain size proportions, were prepared for filling missing portions of the original painted plaster. The effects of the mineralogical nature and size of the aggregates on the characteristics and properties of the mixes were investigated in relation to the microstructure, physical-mechanical features and resistance to salt ageing. At the end of the experimental campaign, the overall performances were evaluated.

In recent years, due to the low energy utilization of the whole life-cycle of buildings and the di-minished indoor and outdoor comfort of buildings and the impact on the surrounding environ-ment caused by the carbon emissions of the building life-cycle, the establishment of a whole life- cycle carbon emission model for buildings to improve their energy utilization at all stages of their life-cycle has received unprecedented attention. In China, the construction industry has become a major carbon emitter, and traditional houses, as a green development building type, are an effec-tive way to achieve carbon neutrality in buildings, but the existing green building evaluation system lacks quantitative indicators of carbon emissions in the building life-cycle. The exclusive evaluation indexes for regional and characteristic buildings, such as traditional houses, are ne-glected; This study explored the formula for calculating the life-cycle carbon emissions model of traditional residential houses under a carbon emission intervention and used real measurements of the physical environment and comparative analysis of the limitations of existing local stand-ards; The results showed that the carbon emission calculation formulas for each stage of the life-cycle of traditional residential houses must be established by combining the selection of local building materials, and the materials for sustainable energy and carbon sinks of green systems. Based on the results of indoor and outdoor heat and humidity environmental tests of residential houses and an analysis of the limitations of existing evaluation indexes due to locality, four im-portant factors affecting locality green buildings in terms of energy utilization, site ecology and landscape, land saving and material saving were extracted; on this basis, the whole life-cycle carbon emission model of traditional residential houses is constructed by combining the existing green building evaluation standards with the carbon emission indexes of the life-cycle of tradi-tional residential houses.

Background: The diagnosis of metabolic syndrome (MetS) is a challenge in people with spinal cord injury (SCI). We aimed at identifying clinical risk factors or early markers of MetS in SCI that would facilitate a timely diagnosis and implementation of preventive/therapeutic strategies. Methods: 168 patients with chronic (>1 year) SCI underwent clinical and biochemical evaluations. MetS was diagnosed according to modified criteria of the International Diabetes Federation validated in people with SCI. Results: MetS was diagnosed in 56 of 132 men (42.4%) and 17 of 36 women (47.2%). At univariate regression analyses, putative predictors of MetS were an older age, a higher number of comorbidities, a lower insulin-sensitivity, the presence and intensity of pain, a shorter injury duration, a poorer leisure time physical activity (LTPA) and an incomplete motor injury. At the multiple regression analysis, a significant independent association with MetS only persisted for a poorer LTPA in minutes/week (OR: 0.998, 95%CI: 0.996, 0.999) and more severe pain symptoms as assessed by numeral rating scale (OR: 1.353, 95%CI: 1.085, 1.793). Conclusions: In patients with SCI, intense pain symptoms and poor LTPA may suggest a high likelihood of MetS, regardless of age, SCI duration, motor disability degree, insu-lin-sensitivity and comorbidities.

The advancement in the production and usage of the cerium oxide nanoparticles have diverted the attention of scientists towards their usage in medical field and therapeutic usage. The clinical usage of these Nano ceria is based on their ability to moderate the oxidative stress and this is only because of their ability to change their valent state from +3 to +4 which makes them ideal for scavenging radicals for use in a number of systemic and neurodegenerative disorders. This review aims to synthesize the basic methods used for the synthesis of nanoparticles along with the use of ligand, stabilizing agent and other components. This review also concludes that how various physical and chemical properties of nanoparticles effect the basic biological activities such as antimicrobial activity, cytotoxicity and many others. However, during the standardization, some of the physiochemical properties, methods used for preparation and catalytic abilities must be taken into account.

Reconfigurable computing is becoming ubiquitous in the form of consumer-based Internet of Things (IoT) devices. Reconfigurable computing architectures have found their place in safety-critical infrastructures such as the automotive industry. As the target architecture evolves, it also needs to be updated remotely on the target platform. This process is susceptible to remote hijacking, where the attacker can maliciously update the reconfigurable hardware target with tainted hardware configuration. This paper proposes an architecture of establishing Root of Trust at the hardware level using cryptographic co-processors and Trusted Platform Modules (TPMs) and enable over the air updates. The proposed framework implements secure boot protocol on Xilinx based FPGAs. The project demonstrates the configuration of the bitstream, boot process integration with TPM and secure over-the-air updates for the hardware reconfiguration.

We have shown that our varying physical constant model is consistent with the recently published variational approach wherein Einstein equations are modified to include the variation of the speed of light c, gravitational constant G and cosmological constant Λ using the Einstein-Hilbert action. The general constraint resulting from satisfying the local conservation laws and contracted Bianchi identities provides the freedom to choose the form of the variation of the constants as well as how their variations are related. When we choose dG/Gdt=3dc/cdt, ̇the same as in our quasi-phenomenological model, c=c₀ exp⁡(a^α-1), G=G₀ exp⁡[3(a^α-1)] and Λ=Λ₀ exp⁡[(a^-α-1)], where a is the scale factor and α=1.8, we are able to confirm the success of our the model in explaining three astrometric anomalies and the null results on the variation of G and the fine structure constant. We show that the model: (a) fits the supernovae 1a observational data better than the ΛCDM model; (b) determines the first peak in the power spectrum of the cosmic microwave background temperature anisotropies at multipole value of l=217.3; (c) calculates the age of the universe as 14.1 Gyr; and (d) finds the BAO acoustic scale to be 145.2 Mpc. These numbers are within less than 3% percent of the observed values and the values obtained by the ΛCDM model. Surprisingly we find that the dark-energy density is negative in a universe that has significant negative curvature and whose expansion is accelerating at a faster rate than predicted by the ΛCDM model.

Objective: To assess the functionality of the affected upper limb in children diagnosed with hemiplegia aged between 4 and 8 years after applying low-intensity modified constraint-induced movement therapy(mCIMT). Methods: Prospective case series study. A mCIMT protocol was applied for five weeks, with two hours of containment per day. The study variables were: quality of movement of the upper limb, spontaneous use, participation of the affected upper limb in activities of daily living, dynamic joint position, grasp-release action, grasp strength, supination and extension elbow movements. Four measurements were performed, using the QUEST scale, the SHUEE Evaluation, a hand dynamometer and a goniometer. Results: The sample was composed of 8 children with moderate manual ability. Statistically significant differences were detected in all the studied variables (p<0.05). The greatest increase occurred in spontaneous use from assessment 1-4 (p = 0.01), reaching 88.87% active participation in bimanual tasks. The quality of movement of the upper limb obtained a significant value due to the increase in dissociated movements and grasp (p = 0.01). Conclusion: A low dose (50 hours) of mCIMT increased the functionality of children diagnosed with congenital hemiplegia between 4 and 8 years of age with moderate manual ability.

The COVID-19 outbreak has focused attention on the use of social distancing as the primary defence against community infection, yet forcing social animals to maintain that physical distance has presented significant challenges for health authorities and law enforcement. Anecdotal media reports suggest widespread dissatisfaction with social distancing as a policy, yet there is little prior work aimed at measuring community acceptance of social distancing. In this paper, we propose a new approach to measuring attitudes towards social distancing by using social media and sentiment analysis. Over a 4 month period, we found 82.5% of tweets were in favour of social distancing. The results indicate a widespread acceptance of social distancing in the community. We conclude by examining options for estimating the optimal (minimal) social distance required at scale, and the implications for securing widespread community support and acceptance of public health messaging.

Is the amount of “greenness” within a 250-meter, 500-meter, 1000-meter or a 2000-meter buffer surrounding a person’s home a good predictor of their physical health? The evidence is inconclusive. We reviewed Web of Science articles that used geographic information systems buffer analyses to identify trends between physical health, greenness, and distance within which greenness is measured. Our inclusion criteria were: (1) use of buffers to estimate residential greenness; (2) statistical analyses that calculated significance of the greenness-physical health relationship; and (3) peer-reviewed articles published in English between 2007 and 2017. To capture multiple findings from a single article, we selected our unit of inquiry as the analysis, not the article. Our final sample included 260 analyses in 47 articles. All aspects of the review were in accordance with PRISMA guidelines. Analyses were independently judged as more, less, or least likely to be biased based on the inclusion of objective health measures and income/education controls. We found evidence that larger buffer sizes, up to 2,000m, better predicted physical health than smaller ones. We recommend that future analyses use nested rather than overlapping buffers to evaluate to what extent greenness not immediately around a person’s home (i.e., within 1,000-2,000m) predicts physical health.

Introduction: Agricultural practices significantly influence soil microbial populations and physicochemical properties, which are crucial for crop growth and quality. This study aims to investigate the impact of different agrochemical applications on soil microbial dynamics, soil physicochemical properties, as well as yield and proximate properties of maize. Methods: Carefully gathered topsoil samples at depths ranging from 1 to 15 cm, were transported to Jimma University to cultivate maize. Over a period of up to 120 days, soil and maize samples were collected at specified days to analyze various parameters, including soil pH, microbial populations, as well as nutrient content both in soil and plants. The collected data was statistically analyzed using one-way ANOVA, with a significance level of p < 0.05. Results: The soil bacterial and fungal populations were measured on days 5, 10, 20, 40, 80, and 120. The highest total mesophilic bacterial count (TMBC) was measured in the pots containing compost (G) and the lowest in pots that received macronutrient fertilizers and glyphosates (B) (i.e. 91.8 x 105 and 13.13 x 105 cfu/g of soil, respectively). The highest total mesophilic fungal count (TMFC) was observed in pots containing glyphosates and compost (F) (i.e. 67.25 x 104 cfu/g soil) and again the lowest in pot treated with macronutrient fertilizers and glyphosate (B) (i.e. 3.23 x 104 cfu/g soil). Moreover, the pots treated with macronutrient fertilizers and glyphosate (B), macronutrient fertilizers (A), and micronutrient fertilizers (C) exhibited the lowest levels of Fe and Zn. Furthermore, the pots receiving macronutrient fertilizer combined with glyphosate (B), as well as those receiving macronutrient fertilizers (A) alone had the lowest concentrations of Mn and Cu micronutrients. Finally, in maize the lowest protein, fats, and carbohydrates (g/100g) were found in the pots treated with macronutrient fertilizer combined with glyphosate (B, 2.21 ± 0.2), micronutrient fertilizer (C, 8.57 ± 0.25), and glyphosates only (D, 57.34 ± 0.1). Maize treated with compost (G) showed the highest levels of Fe, Cu, and Zn, while macronutrient fertilizer combined with glyphosate (B) resulted in the lowest content of these micronutrients. Additionally, maize receiving micronutrient fertilizer (C) had the highest concentration of Mn, whereas those treated with glyphosates (D) had the lowest. Conclusions: Significant variations in soil’s mesophilic bacterial and fungal populations, micronutrient levels, and nutritional composition were observed, indicating treatment-related changes. Generally, treatment with micromineral fertilizer combined with glyphosate (B) seemed to deplete the soil while compost treatment improved. Compost-treated soils exhibited the highest mesophilic bacterial and fungal count, as well as Fe and Zn micronutrient concentrations. The use of agrochemicals also had a negative effect on maize yield quality. The fluctuations in the soil parameters underscore the multifaceted effects of agrochemical treatments.

Background: Targeting Hepatitis B virus (HBV) infection in human is crucial due to its adverse. Herbal medicine has long been significant in this regard, with flavonoids demonstrating promising results. Hence, establishing a way of identifying flavonoids with anti-HBV activities is the aim of the present study. Methods: Flavonoid structures with anti-HBV activities were retrieved. A flavonol-based pharmacophore model was established using LigandScout v4.4. Screening was performed using the PharmIt server. A QSAR equation was developed and validated with independent sets of compounds. Applicability domain (AD) was defined using Euclidean distance calculations for model validation. Results: The best model, consisting of 57 features was generated. HTS using the flavonol-based model resulted in 509 unique hits. The model's sensitivity and specificity were 71% and 100%, respectively. The QSAR model with two predictors, x4a and qed, exhibited strong predictive performance with an adjusted-R² value of 0.85 and 0.90 of Q2. Conclusion: The QSAR model has been validated with two separate chemical sets, guaranteeing the model's reproducibility and usefulness for other flavonols by utilizing the predictive characteristics of X4A and qed. These results provide new possibilities for discovering future anti-HBV drugs by integrating modeling and experimental research.

The flavonoid silymarin (SMN) has been widely used in preclinical and clinical studies to treat various types of cancer, either alone or in combination with chemotherapy agents. Herein, we investigated the therapeutic efficacy of SMN and its combination with capecitabine (CAP) and irinotecan (IRI) in a mouse model of colon cancer. A modified diet supplemented with SMN (2500 ppm) with mono- and combined therapy of CAP and IRI were used following 1, 2 dimethylhydrazine (DMH)-induced colon cancer. The lipid profile, liver function tests, and cytokine levels were measured. Additionally, the lipid peroxidation and inflammation indices as well as the antioxidant activities were examined. Eventually, western blotting analysis for colonic BAX and Bcl-2 levels and histopathological examination of colon sections were carried out. SMN alone and in combination with the chemotherapeutic agents could attenuate the DMH-induced hyperlipidemia and elevated liver function enzyme levels. SMN supplementation with chemotherapy agents could also improve antioxidant activity and reverse the elevated levels of lipid peroxidation and inflammatory markers. Furthermore, significant upregulation of BAX and downregulation of Bcl-2 were observed. Besides, carcinogen-induced polyp multiplicity, dysplastic, and inflammatory changes were ameliorated considerably by treatment regimens. Our results showed that the potential anticancer properties of SMN could enhance the therapeutic effects of chemotherapy agents and reduce hepatotoxicity.

Mycelial cultures of Lentinula edodes, an edible and medicinal mushroom, have been used in our previous research to obtain selenium-containing immunomodulatory preparations. Our current attempts to obtain a new preparation containing both selenium and zinc, two micronutrients necessary for the functioning of the immune system, extended our interest in the simultaneous accumulation of these elements by mycelia growing in media enriched with selenite and zinc(II) ions. Subsequently, we have studied the effects of new L. edodes mycelium water extracts with different proportions of selenium and zinc concentrations on activation of T cell fraction of human peripheral blood mononuclear cells (PBMCs). Flow cytometry analysis was used to measure the expression of activation markers on human CD4+ and CD8+ T cells stimulated by anti-CD3 and anti-CD3/CD28 antibodies (Abs). It was demonstrated that all extracts with different proportions of polysaccharides, selenium and zinc tended to upregulate the expression of all activation markers on both types of T cell populations stimulated in parallel with anti-CD3/anti-CD28 beads, however, statistically significant changes were observed for PD-1 and CD25 antigens on CD8+ T cells. The selenium and zinc content in the examined preparations modified the immunomodulatory activity of mycelial polysaccharides, however, the mechanisms of action of various active ingredients of the mycelial extracts seem to be different.

The conventional phytopathogen Pseudomonas syringae has been identified several significant virulence determinants against Caenorhabditis elegans, but their mechanisms of action remain elusive. Here, we report the nematicidal activity and action receptor of a methyl-accepting chemotaxis protein (MCP03) of a wild-type P. syringae MB03 against C. elegans. Purified MCP03 exhibited significant nematicidal toxicity against C. elegans, with a half-lethal concentration of 124.4 μg mL1, and detrimental effects on the growth and brood size of C. elegans. Additionally, MCP03-treated worms showed severe pathological destruction of the intestine and ovary, and depressed wrinkles of the cuticle. Through yeast two-hybrid assays, we identified a subunit of a COP9 signalosome, namely CSN-5, functionated as an action receptor of MCP03. In vitro pull-down and in vivo co-localization assays verified the binding interaction between MCP03 and CSN-5. RNA interference assays confirmed that MCP03 acts on CSN-5 to adversely affect the brood size, growth, and cuticle integrity of C. elegans. Following MCP03 infection, the expression of several genes relative to reproduction, growth, and cuticle formation, such as kgb-1, unc-98, and col-117, were significantly downregulated, which implicated the pathological changes of MCP03-treated nematodes. Thus, this study demonstrates that MCP03 acted on the receptor protein CSN-5 causing lethality and detrimental effects on the fertility, growth, and morphogenesis of C. elegans, which will provide new insights into the signaling pathways and mechanism underlying the nematicidal action of MCP03 towards C. elegans.

The serine proteases CAP1/Prss8 (prostasin) and CAP3/St14 (matriptase) are identified as ENaC channel-activating proteases in vitro highly suggesting that they are required for proteolytic activation of ENaC in vivo. The present study tested whether CAP3 is relevant for renal proteolytic ENaC activation and affects ENaC-mediated Na+ absorption following Na+-deprivation conditions. CAP3 knockout mice exhibit significant decrease in CAP1 protein expression with altered ENaC subunit and decreased pNCC protein abundances, but overall maintain sodium balance. RNAscope-based analyses reveal co-expression of CAP3 and CAP1 with alpha ENaC in distal tubules of the cortex from wildtype mice. Double CAP1/CAP3-deficiency maintained Na+ and K+ balance on Na+-deprived diet, restored ENaC subunit protein abundances but showed reduced NCC activity under Na+-deprivation. Overall, our data clearly show that CAP3 is not required for direct proteolytic activation of ENaC, but for its protein abundances. Our study reveal a complex regulation of ENaC by these serine proteases on the expression level rather than on its proteolytic activation.

Background: Physical activity (PA) has paramount importance for achieving good health and an active lifestyle among university students. Quality physical education (QPE) program ensures the attainment of sustainability in PA. Motivation can be considered a critical factor in promoting PA in students. However, motivation alone cannot bring inclusivity unless quality aspects are not being incorporated thoughtfully into physical education (PE) programs. Aims: As such this study aimed at examining three research questions: i) do the motive of PA participation can be enhanced through the quality provision of PE programs in university settings ii) does the quality provision of PE help promote sustainable PA among adolescents? and iii) whether or not this carry-over process is influenced by gender. Methods: This cross-sectional study recruited N = 610 (male = 467) & female = 143) university students. Students who studied PE as one of their course subjects were only included in this study. They participated in > 27 different sports and had a mean age of 20.76 (SD = 3.47) years and a mean of 4.70 (SD = 4.93) years of athletic experience. Descriptive (mean, SD) statistics, Pearson’s correlation, and regression analysis were used to meet the objectives. To examine the variables’ differences in gender, data were then computed using a 2 (Gender) by 2 (Type of Sport: Individual vs. Team) MANCOVA, with the covariate being age. Results: The factors provided sound reliability scores and highlighted positive correlations between QPE and exercise needs satisfaction. However, the factors lacked establishing correlations with PA. The perceived competence for exercise needs satisfaction reported differences in sexes, with the male being scored higher. Furthermore, QPE did not show any significant differences in gender. In comparison to females, males showed higher mean scores in the PA. Conclusion: The provision of QPE is identified as a pivotal factor in determining the competence of exercise satisfaction among students. QPE provision was adequate in the university, however, it could not promote PA among females as expected.

Background: Although the use of regular replacement therapy including emicizumab for severe hemophilia has been spread, the assessment of the hemostatic ability using routine activated partial thromboplastin time (APTT) is still difficult in patients being treated with emicizumab. Methods: The hemostatic ability in patients treated with FVIII concentrate or emicizumab was evaluated by APTT, thrombin time (TT) and a small amount of tissue factor induced FIX activation assay (sTF/FIXa) using a clot waveform analysis (CWA). Results: FVIII activities based on a CWA-TT were significantly higher than those based on a CWA-APTT or chromogenic assay. FVIII activities based on the three assays in plasma without emicizumab were closely correlated, and those in plasma with emicizumab based on a CWA-TT and chromogenic assays were also closely correlated. The CWA-APTT and CWA-TT showed different patterns in patients treated with FVIII concentrates from those treated with emicizumab. In particular, the CWA-TT in patients treated with FVIII concentrate showed that the peak heights were significantly higher in platelet-rich plasma than in platelet-poor plasma. In plasma with approximately 16% of FVIII activity based on APTT assay from patients treated with FVIII concentrate, the peak height on the CWA-sTF/FIXa showed a higher hemostatic abilitythan normal plasma. Conclusions: The CWA-TT can measure the FVIII activity in patients treated with emicizumab. Although routine APTT evaluations demonstrate a low hemostatic ability in patients treated with FVIII concentrate, the CWA-TT and CWA-sTF/FIXa show hypercoagulability in those patients.

The multitarget therapeutic strategy, as opposed to the more traditional ‘one disease-one tar-get-one drug’, may hold promise in treating multifactorial neurodegenerative syndromes, such as Alzheimer’s disease (AD) and related dementias. Recently, combining a photopharmacology approach with the multitarget-directed ligand (MTDL) design strategy, we disclosed a novel donepezil-like compound, namely 2-(4-((diethylamino)methyl)benzylidene)-5-methoxy- 2,3-dihydro-1H-inden-1-one (1a), which in the E diastereomeric form (and about tenfold less in the UV-B photo-induced isomer Z) showed the best activity as dual inhibitor of the AD-related targets acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B). Herein, we investigated further photoisomerizable 2-benzylideneindan-1-one analogs 1b-h with the unconjugated tertiary amino moiety bearing alkyls of different bulkiness and lipophilicity. For each compound the thermal stable E diastereoisomer, along with the E/Z mixture as produced by UV-B light irradia-tion in the photostationary state (PSS, 75% Z), was investigated for the inhibition of human ChEs and MAOs. The pure E-diastereoisomer of the N-benzyl(ethyl)amino analog 1h achieved low nanomolar AChE and high nanomolar MAO-B inhibition potencies (IC50s 39 and 355 nM, re-spectively), whereas photoisomerization to the Z isomer (75% Z in the PSS mixture) resulted in a decrease (about 30%) of AChE inhibitory potency, and not in the MAO-B one. Molecular docking studies were performed to rationalize the different E/Z diastereoselectivity of 1h toward the two target enzymes.

In this contribution, unmodified silver nanoparticles were synthesized and characterized for their size and morphological properties. Thereafter, their peroxidase-like activity as the common catalytic property of silver nanoparticles was investigated by catalyzing the oxidation of 3,3’,5,5’-tetramethyl-benzidine (TMB) as peroxidase substrate, exhibiting, a specific activity as high as 5.4 µM min^-1 for the as-prepared unmodified silver nanoparticles. The stability of the catalytic activity of the as-prepared nanozymes was also checked upon their storage at ambient temperature within 7 days at different storage conditions. The results revealed that the peroxidase-like activity of unmodified silver nanoparticles was approximately retained at about 75%, and 63% after 7 days exposing daylight and air oxygen, in order. The shelf-life (storage stability) of the as-prepared nanozymes was also investigated at usual storage conditions (i.e., 4 ℃ under dark), revealed that the nanozymes saved their activity about 96% of their initial activity after 10 days of storage at 4 ℃ under dark conditions.

The growing increase in infections caused by C. tropicalis, associated with its drug resistance and consequent high mortality, especially in immunosuppressed people, today generates a serious global public health problem. In the search for new potential drug candidates that can be used as treatments or adjuvants in the control of infections by these pathogenic yeasts, the objective of this research was to evaluate the action of isoespintanol (ISO) against the formation of biofilms fungal, the mitochondrial membrane potential (∆Ψm) and its effect on the integrity of the cell wall. We report the ability of ISO to inhibit the formation of biofilms by up to 89.35%, in all cases higher than the values expressed by amphotericin B (AFB). Flow cytometric experiments using rhodamine 123 (Rh123) showed the ability of ISO to cause mitochondrial dysfunction in these cells. Likewise, experiments using calcofluor white (CFW) and analyzed by flow cytometry, showed the ability of ISO to affect the integrity of the cell wall by stimulating chitin synthesis; these changes in the integrity of the wall were also observed through transmission electron microscopy (TEM). These mechanisms are involved in the antifungal action of this monoterpene.

The COVID-19 pandemic has caused detrimental impacts on different population groups throughout the world. This study aimed to explore the impacts of the COVID-19 pandemic’s mandatory lockdown protocols on activities and mental health conditions of community-dwelling older people in Jakarta, Indonesia. A qualitative design using one-on-one in-depth interviews was employed to collect data from the participants (n=24) who were recruited using the snowball sampling technique. Data analysis was guided by a qualitative data analysis framework. The findings showed that before the COVID-19 outbreak participants engaged in different kinds of regular individual and social activities. However, the COVID-19 outbreak and its mandatory lockdown protocols significantly influenced both their activities and social life, which led to social disconnection and financial difficulties for them. COVID-19 outbreak, mandatory lockdown protocols, and disruption of individual and social activities of the participants also caused mental health challenges to them, including feelings of loneliness, loss, sadness, stress, and anger. The findings suggest that there is a need for intervention programs addressing the socio-economic and mental health impacts of the COVID-19 pandemic on older populations to help them cope with these challenges. Future studies involving large-scale older populations to comprehensively understand COVID-19 impacts on them are recommended.

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

This study reports a correlation between EEG and structural brain changes in patients after severe traumatic brain injury in a coma. The novelty of our approach was based on the combination of structural visualization (MRI) and functional neuroimaging (EEG) during tactile stimulation. The structural morphometry indicated a decrease of whole-brain cortical thickness, the gray-matter volume of the cortex, and subcortical structures in comatose patients compared to healthy subjects. In resting-state EEG, coma patients had significantly higher power of the slow-wave activity of 2-6 Hz and significantly less power of the alpha and beta rhythm. Importantly, coma patients showed a significant decrease of theta-rhythm power in tactile stimulation compared to the resting state, and this EEG pattern was not found in the control group. The decrease of the theta-rhythm power significantly correlated with the better outcome from a coma. Spectral changes in EEG in response to tactile stimuli showed no association with brain morphometric measures in healthy controls. In patients, decreasing theta-rhythm power correlated positively with the volume of whole-brain gray matter, right putamen, and insula; and negatively with the volume of damaged brain tissue. Increasing beta-rhythm power, specific tactile EEG response for a healthy brain, correlated with the cortical thickness of the somatosensory Paracentral and Precentral area. The observed decrease of gray-matter volume indicates brain atrophy in coma patients, which could be associated with neurodegeneration induced by injury. Our results also demonstrate that slow-wave desynchronization, as a nonspecific response to tactile stimulation, can serve as a sensitive index of morphometric changes after brain injury and coma outcome.

This study applies a cluster analysis to identify typical physical activity (PA) and sedentary behaviour (SB) patterns in people with chronic obstructive pulmonary disease (COPD) before starting pulmonary rehabilitation (PR). We implemented an observational design which assessed baseline data on objectively measured PA and SB from the STAR (Stay Active after Rehabilitation) study. 355 persons wore a accelerometer (Actigraph wGT3X) for seven days before the start of their PR. Sociodemographic and disease-related parameters were assessed at the start of PR. We applied cluster analysis and compared groups applying univariate variance analyses. Data was available for 326 persons (31.6% women; age ø = 58 yr.). Cluster analysis revealed four movement clusters with distinct PA and SB patterns: sedentary non-movers (28.5%), sedentary occasional movers (41.7%), sedentary movers (19.6%), and sedentary exercisers (10.1%). The four clusters showed very different levels of moderate PA before rehabilitation (Ø daily minutes: 9; 28; 38; 70). Notably, all four clusters displayed considerably long average sitting time per day (Ø daily minutes: 644; 561; 490; 446). The groups differed significantly in disease-related parameters of GOLD severity, FEV1, CAT, and 6-Min-Walk-Test. In addition to PA promotion, PR programs should consider the reduction of sitting time as a valuable goal.

With the increasing pace of global warming, it is important to understand the role of meteorological factors in influenza virus (IV) epidemics. In this study, we investigated the impact of temperature, UV index, humidity, wind speed, atmospheric pressure, and precipitation on IV activity in Norway, Sweden, Finland, Estonia, Latvia and Lithuania during 2010-2018. Both correlation and machine learning analyses revealed that low temperature and low UV indexes were the most predictive meteorological factors for IV epidemics in the Northern European countries. Our in vitro experiments confirmed that low temperature and UV radiation preserved IV infectivity. Associations between these meteorological factors and IV activity could improve surveillance and promote development of accurate predictive models for future influenza outbreaks in Northern Europe.

Synthesis of new series of 1-phenyl-3-(4-(pyridin-3-yl) phenyl) urea derivatives and its in vitro antiproliferative activities against NCI-60 human cancer cell lines of nine different cancer types are described. Fourteen compounds 5a-n have been synthesized with three different hydrogen bondable moieties (4-hydroxylmethylpiperidinyl and trimethoxyphenyloxy and 4-hydroxyethylpiperazine) attached to the core structure 1-phenyl-3-(4-(pyridin-3-yl) phenyl) urea. Different substituents with different π and σ values were added on the terminal phenyl group. Compounds with 4-hydroxymethylpiperidine moiety showed higher mean percentage inhibition values over the 60-cell line panel at 10-µM concentration. They showed broad-spectrum antiproliferative activity over many cell lines of different cancer types. For instance, compound 5a elicited some lethal rather than inhibition effects on SK-MEL-5 melanoma cell line, 786-0, A498, RXF 393 renal cancer cell lines, and MDA-MB-468 breast cancer cell line by 146.1, 108.7, 136.2, 134.8, 116.6 % at 10 µM, respectively. Compounds 5a-e exhibited superior antiproliferative activity than Paclitaxel and Gefitinib against the most sensitive cell lines. Two compounds, 5a and 5d showed promising mean growth inhibitions and thus were further tested at five-dose testing mode to determine their IC₅₀ values. The data revealed that 5a and 5d urea compounds are the most active derivatives with significant efficacies and superior potencies than Paclitaxel in 21 different cancer cell lines, belonging particularly to renal cancer and melanoma cell lines. Moreover, 5a and 5d had superior potencies than Gefitinib in 38 and 34 cancer cell lines, respectively; belonging particularly to colon cancer, breast cancer and melanoma cell lines.

Hispanics are disproportionately affected by low rates of physical activity and high rates of chronic diseases. Hispanics generally and Mexican Americans specifically are underrepresented in research on physical activity and its impact on mental well-being. Some community-based interventions have been effective in increasing physical activity among Hispanics. This study examined data from a sample of low-income Hispanic participants in free community exercise classes to characterize the association between self-reported frequency of exercise class attendance, intensity of physical activity, and participant well-being. As part of two cross-sectional samples recruited from a stratified random sample of community exercise classes, 302 participants completed a questionnaire consisting of a modified version of the Godin-Shephard Leisure-Time Exercise Questionnaire (LTEQ) and the Mental Health Continuum Short Form (MHC-SF). Adjusted binary logistic regression analyses indicated that those who achieve moderate and strenuous self-reported physical activity have 130% higher odds (p = 0.0422) of positive mental well-being after adjustment for age, attendance, and self-reported health. This study provides evidence that physical activity intensity and time are associated with flourishing mental health among Hispanics. The study provides insight into the planning and development of community-based physical activity programming tailored to low-income populations.

The use of Lactic Acid Bacteria (LAB) for probiotic enrichment of minimally processed fruit is a well-established practice in literature. In addition, several LAB demonstrated a strain-specific ability to control harmful microorganisms and decay agents, improving shelf-life, maintaining quality and promoting the safety of fruits and vegetables. Edible coatings can help modulate phenomena of gas exchange and water loss by fruits, representing protection from physical damage and spoilage phenomena linked to oxidation and the development of undesired microorganisms. At the same time, the coating can represent an innovative delivery matrix for the LAB strains of potential interest to improve safety and quality in the postharvest management of fruits. In this work, five Lactiplantibacillus plantarum strains, previously characterized for their probiotic and antifungal activity, have been incorporated into a sodium alginate coating to develop edible probiotic coatings with antifungal properties for table grapes cv. Italia. The transfer of probiotics and their survival were evaluated by comparing coated and uncoated table grapes during 14 days of cold storage at 4 °C. The alginate edible coating increased the number of probiotics transferred to the surface of the berries from about 5 to more than 7 Log CFU/g, with a crucial impact on the potential functional attributes of the final product. The ability of the functionalised coatings to counteract the decay development was evaluated on table grapes berries artificially contaminated with Aspergillus niger CECT 2805. A significant reduction of lesion diameter was observed in alginate coating with L. plantarum 11-A. The lesion diameter reduction was also accompanied by the reduction of the symptoms of infection, such as browning around the wound. These results suggest the application of selected strains of L. plantarum as promising bio-resources to enhance the overall value of ready-to-eat fruits and vegetables, particularly in combination with edible coating as a carrier matrix. While a strain-dependent effect was not detected with respect to the improvement of the number of cells in the edible coating, a variability depending on the biotype used was detected for the properties linked to biocontrol, suggesting that the inclusion in edible packaging may represent an innovative criterion in the selection of lactobacilli to be applied postharvest.

The pharmaceutical industry usually utilizes either hydrophobic or hydrophilic substances extracted from raw plant materials for preparing a final product, However, the plant material waste still contain substances with an opposite solubility. The aim of this study was to enhance the comprehensive usability of plant materials by developing a new non-wasting extraction method for eucalypt leaves and by investigating the phytochemical and pharmacological properties of eucalypt extracts and their 3D-printed dosage forms. The present extraction method enabled to prepare both hydrophobic soft extracts and hydrophilic (aqueous) dry extracts. We identified total 28 terpenes in the hydrophobic soft extract. In the hydrophilic dry extract, total 57 substances were identified, and 26 of them were successfully isolated. The eucalypt extracts studied showed a significant antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Candida albicans, Corynebacterium diphtheriae gravis, and Corynebacterium diphtheriae mitis. The anti-inflammatory activity of the dry extract was studied with a formalin oedema model in mice. The maximum anti-exudative effect of the dry extract was 61.5% at a dose of 20 mg/kg. The composite gels of polyethylene oxide and eucalypt extract were developed, and the key process parameters for semi-solid extrusion (SSE) 3D printing of such gels were verified. The SSE 3D-printed preparations of novel synergistically acting eucalypt extracts could have uses in antimicrobial and anti-inflammatory medicinal applications.

The aim of the study is to explore how sharing status updated and receiving Likes on Facebook, as a form of positive social feedback, correlates with current and perceived changes in Quality of Life (QoL) Sample consisted of 1577 adult Facebook users (76.3% females; 65.9% aged 18-24, 21.9% aged 25-30, 12.3% aged &gt; 30 years old). The study employed a longitudinal approach, collecting Facebook data from adult users over a 12-month period using the Graph API. Data were divided into 12 monthly segments. Two monthly indicators were calculated: the percentage of textual status updates and the average number of Likes per post. Current and perceived changes in Quality of Life (QoL) were administered as self-report measures. The findings indicated a positive correlation between the frequency of textual Facebook posts and the average received Likes. Furthermore, receivign more Likes was positively associated with a higher current QoL, and perceived improvements in QoL correlated with an increase in Likes over time. The study suggests that online positive social feedback, measured through Likes on Facebook, is associated with both current QoL and perceived improvements in QoL among adult Facebook users. This highlights the potential impact of online social interactions on individual well-being.

Cancer is a devastating disease with female breast cancer becoming the leading cause of global cancer morbidity. Herein we report the design and synthesis of a sorafenib analog 1A and its base-promoted arranged compound 1A2. Their in vitro cytotoxicity and potencies in EFGR inhibition study revealed that compound 1A displayed good antiproliferative activity in MDA-MB-231 (breast) cells with an IC50 value of 16.18±1.42 μM. Crystallization 1A2 affored 1A2a as a solvate with dichloromethane which was explicitly confirmed by the single crystal X-ray diffraction analysis.

Background and objectives: Musculoskeletal (MSK) pain significantly impacts physical activity and quality of life in the elderly, potentially influencing mortality. This study explored the relationship between MSK pain, physical activity, muscle mass, and mortality among older adults. Material and Methods: We studied 1000 participants of the Korean Longitudinal Study on Health and Aging (KLoSHA), a prospective, population-based cohort study of people aged 65 years or older. Survival status was tracked over a 5-year period. Correlations between Low back pain (LBP), knee pain, regular exercise, appendicular skeletal muscle mass (ASM), and other variables were analyzed. Logistic regression analyzes were used to identify independent risk factors for mortality. Results: Of the total participants, 829 (82.9%) survived after a 5-year period. Survivors tended to be younger, had a higher BMI, and were more active in regular exercise. In contrast, non-survivors exhibited a higher prevalence of both LBP and knee pain, along with increased instances of multiple MSK pain. Lower ASM correlated moderately with LBP and knee pain, whereas higher ASM was associated with regular exercise Lower ASM was moderately associated with LBP and knee pain, while higher ASM correlated with engagement in regular exercise. There was a moderate correlation between LBP and knee pain, both of which were associated with a lack of regular exercise. Age, sex, ASM, and regular exercise were significant predictors, even though MSK pain itself did not directly predict all-cause mortality. Conclusions: This study demonstrated the independent association between ASM, regular exercise, and mortality. Although MSK pain did not directly correlate with all-cause mortality, the non-survivor group had higher levels of both single and multiple MSK pain. Recognizing the interplay of MSK pain, physical activity, and muscle mass for older adults, the research underscores the need for holistic strategies to enhance health outcomes in older individuals with MSK pain.

Four models of Ce(III) complexes with four ligands based on a 1,2,3-triazole derivatives were studied at four DFT levels. The effect of different ligands on the atomic charge value on the cerium ion was analyzed. Several relationships were clearly established between this atomic charge and that of the surrounding atoms, as well as with several geometric parameters of the ligand and with the molecular properties of the Ce(III) complex. The experimental IR and Raman spectra of the newly obtained Ce(III) complex with the (pyrrolidin-1-yl)-2H-1,2,3-triazole-4-carboxylate ligand were interpreted based on their comparison to the theoretical scaled ones using the scaling equations determined by two procedures and four DFT levels. Therefore, the structure predicted for the synthesized Ce(III) complex was clearly characterized and confirmed. The potential antioxidant action of Ce(III) complex was elucidated and compared with other Ln(III) complexes in order to find out the differences in their biological activity profiles.

Three new compounds (1, 11 and 12), together with 32 known ones, were isolated from the root bark of Morus alba L. using various chromatographic methods. The structures of the undescribed compounds were elucidated based on 1D, 2D NMR and HRESIMS data analysis, while the known ones were identified by comparison of their spectroscopic data with those reported in the literature. All the isolates were evaluated for their cytotoxic activities against human gastric cancer HGC27 cells by CCK-8 assay. Among them, compounds 5, 8, 10 and 30 exhibited cytotoxic activities on HGC27 cells with IC50 values of 10.24 ± 0.89 μM, 28.94 ± 0.72 μM, 6.08 ± 0.34 μM and 33.76 ± 2.64 μM, respectively. Furthermore, compound 10 was confirmed to reduce proliferation ability, increase apoptosis rate and inhibit cell migration pathway by annexin V/PI double staining experiment, transwell experiment and western blot analysis.

Acetyleugenol is a phytochemical compound with broad effect against infectious diseases and tumors. Here, we extracted, characterized and elucidated the structure of acetyeugenol, for the first time, from the leaves of Acacia nilotica (L.)―a well-known medicinal plant. The broad antibacterial potential of acetyleugenol was first confirmed against seven bacterial pathogenic isolates with best activity against Proteus sp., Salmonella typhi, Staphylococcu aureus, and Streptococcus pneumonia, which showed similar or better zone of inhibition to that of the control amoxicillin. To further investigate its effect against Mycobacterium tuberculosis, acetyleugenol and its indole and phenyl analogs were subjected to molecular docking experiments against two potential tuberculosis drug targets―MtPknE and MtPknB Ser/Thr protein kinases. The results reveal that all of the analogs have improved docking scores comparing to the acetyleugenol. The indole analogs EUG-1 and EUG-3 were more effective with better docking scores for MtPknE with –11.08 and –10.05 kcal/mol, respectively. Similar results were obtained for the MtPknB. In contrast, only the EUG-2 phenyl analog has given rise to similar docking scores for both targets. This opens the door for further comprehensive studies on these acetyleugenol analogs with in vitro and in vivo experiments to validate and get more insights into their mechanisms of action.

The probiotic bacterial strain Lactobacillus plantarum ZS2058 has been proved to manifest comprehensive functions, which were due to ability to synthesise conjugated fatty acids (CFAs). To investigate the specific functions of CFAs produced by this probiotic bacterium, α-linolenic acid was isomerized by Lactobacillus plantarum strain ZS2058, and two different conjugated α-linolenic acid (CLNA) isomers were successfully isolated. These isoforms, CLNA1 (c9, t11, c15-CLNA, purity 97.48%) and CLNA2 (c9, t11, t15-CLNA, purity 99.00%), both showed the ability to inhibit the growth of three types of colon cancer cells in a time- and concentration-dependent manner. In addition, the expression of MDA in Caco-2 cells was increased by CLNA1 or CLNA2, which indicated lipid peroxidation was related to the antiproliferation activity of CLNAs. Examination of the key protein of pyroptosis showed that CLNA1 induced the cleavage of caspase-1 and gasdermin-D, while CLNA2 induced the cleavage of caspase-4, 5 and gasdermin-D. The addition of relative inhibitors could alleviate the pyroptosis by CLNAs. CLNA1 and CLNA2 showed no effect on caspase-3, 7, 9 and PARP-1, which were key proteins associated with apoptosis. And no sub-diploid apoptotic peak appeared in the result of PI single staining test. In conclusion, CLNA1 activated caspase-1 and induced Caco-2 cell pyroptosis, whereas CLNA2 induced pyroptosis through the caspase-4/5-mediated pathway. The inhibition of Caco-2 cells by the two isomers was not related to apoptosis. This is the first report showing the ability of CLNAs to activate antioxidant defenses resulting in pyroptosis.

The morphology and the activity of a submarine caldera, Avyssos, at the northern part of Nisyros volcano in the South Aegean Sea (Greece), has been studied by means of remotely operated underwater vehicle dives. The recorded time series of temperature and conductivity over the submarine volcano have been analyzed in terms of the Generalized Moments Method. The findings of the mathematical analysis shed light on the volcanic activity, but also on the morphology (shape) of the submarine volcano. The conductivity time series indicates the volcano is at rest in agreement with other types of observations. On the other hand, temperature fluctuations, which in general describe a multifractal process, show that the submarine caldera operates as an open system that interacts with its surroundings. This type of analysis can be used as an indicator for the state of activity and the morphological structure (closed or open system) of a submarine volcano.

Origins of the time, mass, electric charges and magnetic monopoles are explained. The energies, electric charges and magnetic charges of the particles are defined as E = cDtDV and |q| = cDt = E/DV, and |q_m| = c²Dt, respectively, for the 3-D quantized spaces warped along the time axis direction of ct in the 4-D Euclidean space. The energy (or mass) and charges (or electric charges and magnetic charges) are the vectors along the time axis of ct in the 4-D Euclidean space. This new concept is closely connected to the wave function of the quantum mechanics. The electric charges, magnetic charges and energies have the property of the space direction independence. Magnetic monopoles (charges) are the force carrying bosons with the inside electric field time loop. Electric monopoles are the elementary fermions. Photon space fluctuations are explained with the quantized magnetic charges.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

The 2020 Elucidating the role of clouds-circulation coupling in climate - Ocean-Atmosphere (EUREC4A-OA) and Atlantic Tradewind Ocean-Atmosphere Mesoscale Interaction Campaign (ATOMIC) campaigns sought to improve the knowledge of the interaction between clouds, convection and circulation and their function in our changing climate. The campaign consisted of numerous research technologies, some of which are relatively novel to the scientific community. In this study we used a saildrone uncrewed surface vehicle to validate satellite and modelled sea surface salinity (SSS) products in the Western Tropical Atlantic. These products include the Soil Moisture Active Passive (SMAP) Jet Propulsion Laboratory (JPL), SMAP Remote Sensing Systems (RSS), and Hybrid Coordinate Ocean Model (HYCOM). In addition to the validation, we investigated a fresh tongue south east of Barbados. The saildrones accurately depicted the salinity conditions and all satellite and modelled products performed well in areas that lacked small-scale salinity variability. However, SMAP RSS 70 km outperformed its counterparts in areas with small submesoscale irregularities while RSS 40 km was better at identifying small irregularities in salinity such as a fresh tongue. These results will allow researchers to make informed decisions regarding the most ideal product for their application and aid in the improvement of mesoscale and submesoscale SSS products, which can lead to the refinement of numerical weather prediction (NWP) and climate models.

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.

The novel ternary composites, BiOBr-TiO2-attapulgite (BTA), were synthesized using a simple hydrothermal and water-bath method, exhibiting excellent photocatalytic performance to mul-tiple xanthates. For BTA photocatalyst, TiO2 and BiOBr were uniformly loaded on the surface of acid-activated attapulgite. As a widely used collector in mining processes, sodium ethyl-xanthate (SEX) was selected as the target pollutant due to its high toxicity. The BTA ternary photocatalyst demonstrated significantly higher adsorption and photocatalytic degradation performance compared to TiO2 nanoparticles, BiOBr nanosheets, and BiOBr-TiO2 heterojunction. Structural characterization and experimental results indicated that the exceptional photocatalytic degrada-tion efficiency of BTA was mainly attributed to the formation of heterojunction between BiOBr and TiO2, as well as the presence of additional active adsorption sites provided by attapulgite. Free radical scavenging experiments and EPR results confirmed that the photogenerated holes were the predominant active species to photodegrade SEX throughout the entire experiment. The LC-MS results provided insight into potential degradation pathways of SEX. This research demonstrates that BTA, as a novel triple composite material, achieves rapid and complete degradation to 20 mg/L SEX within 20 min. This work presents a novel approach to synthesize mineral-based photo-catalysts, which have broad prospects for application in flotation wastewater treatment.

Perilla frutense var. acuta (Lamiaceae) has been used to treat indigestion, asthma, and allergies in traditional medicine. In this study, luteolin 7-O-diglucuronide (1), apigenin 7-O-diglucuronide (2), and rosmarinic acid (3) were isolated from the leaves of P. frutescens var. acuta. Various approaches were performed to investigate the anti-inflammatory activity of the isolated compounds (1-3) and their working mechanisms. In silico docking simulation demonstrated that 1-3 would work as a PPAR-α/δ/γ agonist, and in vitro PPAR-α/δ/γ transcriptional assay showed that the Perilla extract and 3 increased PPAR-α luciferase activity [1.71 and 1.61 times of the control (PPAR-α + PPRE, p < 0.001)]. In the NF-κB luciferase assay, 1 suppressed NF-κB activity the most (56.83 % at 5 µM; 74.96 % at 10 µM; 79.86 % at 50 µM). In addition, 1 and 2 inhibited the mRNA expression of NF-κB target genes, including Il6, Mcp1, and Tnfa, at 50 µM, and 3 suppressed the genes at the mRNA level in a dose-dependent manner. We report that 1 and 2 exert anti-inflammatory effects through NF-κB inhibition, and PPAR-α/NF-κB signaling pathway is related to the anti-inflammatory activity of 3.

Lipases have tremendous potential for industrial use, particularly, those mostly active against water-insoluble substrates, such as triglycerides composed of long-chain fatty acids. However, in most cases, mutants often need to be constructed to achieve optimal performance for such substrates. Protein engineering techniques have been reported as strategies for improving lipase characteristics by introducing specific mutations in the cap domain of esterases or in the lid domain of lipases, or through lid domain swapping. Here, we have improved the lipase character of a lipase, retrieved from the Marine Metagenomics MarRef Database and assigned to the Actinoalloteichus genus (WP_075743487.1), through site-directed mutagenesis and by substituting its lid domain (FRGTEITQIKDWLTDA) by the one of Rhizopus delemar (previously Rhizopus oryzae) lipase (FRGTNSFRSAITDIVF). Results demonstrated that the redesigned mutants gain activity against bulkier triglycerides such as glyceryl tridecanoate and tridodecanoate, olive oil, coconut oil, and palm oil. The absence of a residue in the new lid, present in the original lid, appears to be a key aspect to the increase in lipase character, although full activity recovery is only obtained with lid swapping.

The uneven immunogenicity of the attenuated tetravalent dengue vaccine has created the diffi-culty to achieve a balanced protection against all four serotypes of dengue virus (DENV). To overcome this problem, non-replicative-based vaccines have come into focus as their immuno-genicity is adjustable. This approach is excellent for multivalent vaccines but commonly faces the issue of low immunogenicity. In this present study, we developed a non-replicating dengue vaccine composing of UV-inactivated dengue-2 virus (UV-DENV2) and DENV-2 NS1-279 protein encapsidated within nanoparticles. This vaccine candidate was administered in the presence of BCG cell wall cytoskeleton (BCG-CWS) as an adjuvant. We revealed, here, that encapsidated immunogens with BCG-CWS exerted potent activities on both B and T cells and elicited Th-1/Th-2 responses in mice. This was evidenced by strong neutralizing antibody activity with an unde-tectable antibody enhancing activity in a group of mice receiving encapsidated immunogens with BCG-CWS. Importantly, BCG-CWS significantly augmented antibody-mediated comple-ment-fixing activity, strongly stimulated the antigen-specific polyfunctional T cell responses as well as activated mixed Th-1/Th-2 responses specific to DENV2- and NS1-279 antigens. In conclu-sion, BCG-CWS potently adjuvanted the inactivated DENV-2 and subunit DENV immunogens. The mechanism of adjuvanticity remains unclear. This study revealed the potential use of BCG-CWS in vaccine development.

The aim of this article was to evaluate properties of new polymer material, based on PEEK, for FPDs in patients with parafunctions. Methods: Prospective clinical study involved patients with diagnosed signs and symptoms of parafunctions, restored with 100 units, PEEK based FPDs, veneered with composite material. During one year observation period the following parameters were evaluated: color changes, periodontal indices, treatment success using FDI criteria, occlusal parameters, patient-reported outcome measures (OHIP-49) and occurrence of complications. Results: Spectrophotometry revealed that 63% of bridges experienced changes for L*, a*, b* color parameters, but it was not clinically significant for patients. Periodontal indices (PI, GI, BOP) revealed statistically significant higher values around restorations. According to FDI criteria, therapy was considered successful and 86.7% of FPDs were acceptable. Computerized occlusal analysis demonstrated no significant difference in the number of occlusal contacts and the intensity of relative forces between restoration and control side. Results of OHIP-49 questionnaire showed improved patient’s quality of life. Complications appeared in a limited number of cases. Conclusion: PEEK based FPDs could be indicated for successful prosthodontic rehabilitation in patients with parafunctional activities, but further material improvements and long-term clinical trials should be conducted to analyze performance of this material in challenging cases, for patients with CMD and in implant therapy.

In the current study, the physicochemical and microbiological characteristics of this fermented wheat Hamoun were described in detail, as well as the soil properties where this type of wheat was stored. The results showed that the Hamoum had concentrations of the lactic acid of 0.25 g ± 0.03 for the Simeto variety (nine years of storage), as well as 0.13 g ± 0.02 and 0.17 g±0.06 for the Ofanto variety following three and six months, respectively, of storage. The water content varied between 8.3 - 9.7 % for grain and between 10.8- 11.5 % for flour. The ash content of grain and flour of 1.43 ± 0.02 and 1.63 ± 0.26, respectively, was above the normal standards. According to these results, fermented wheat is appropriate for human consumption. The results also showed that the soil where the wheat was stored comprised mainly clay and had an alkaline pH of 8.2. The isolation and identification of fermentable germs showed the presence of lactic acid bacteria belonging to the genera Lactobacillus (59 %), Pediococcus (18 %), Leuconostoc (17 %), and Streptococcus (6 %). The antibacterial activities of isolated acid bacteria against pathogenic germs Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 9027), Bacillus cereus (ATCC 14579), and Staphylococcus aureus (ATCC 43300) reflected the presence of strong antibacterial activity, with 62.5 % positive interactions and 100 % pathogenic bacteria inhibited by Lactobacillus.

Even after debridement and chemical root canal preparation, multispecies bacterial biofilms can still be found in root canals and dentinal tubules. This demonstrates the necessity of using suitable antibacterial endodontic sealers. Due to their well-known biological qualities, calcium silicate based root canal sealers or “bioceramic’ sealers have recently been launched and can be successful in endodontic procedures. This study's objective was to compare the impact of CerasealR, Total Fill BC SealerR, Bio-C SealerR, AH Plus BioceramicR, K-biocerR and SealiteR on the elimination of a multispecies’ endodontic biofilm at 3, 7 and 14 days. Enterococcus faecalis, Pseudomonas Aeruginosa, Candida Albicans and Proteus Mirabilis were cultured on specific agars and later grown in Brain Heart Infusion broth on hydroxyapatite discs pretreated with collagen type 1 and incubated for 18 days. The resulting biofilm was then placed on a 10mm round shaped blotting paper set on a metallic net in a 6cm petri dish with an orthodontic bend filled with the calcium silicate based root canal sealer in direct contact with the biofilm. In all tested groups, the total bacterial count has significantly decreased between day 3 and day 14 (P<0.05) with no statistically significant differences among the different sealers’ groups at all time points. Sealite group was capable of decreasing the Candida Albicans count significantly between day 3 and day 14 (P<0.05) in comparison with the bioceramic groups. All sealers had antibacterial activity against the multispecies biofilm between day 3 and day 14.

The increasing prevalence of methicillin-resistant S. aureus (MRSA) in the dairy industry has become a fundamental concern. Endolysins are bacteriophage-derived peptidoglycan hydrolases that induce the rapid lysis of host bacteria. We investigated endolysin candidates with lytic activity against MRSA and evaluated the lytic activity of the endolysin candidate against S. aureus and MRSA. To identify endolysins, we used the following bioinformatic strategy: (1) retrieval of genetic information, (2) annotation, (3) selection of MRSA, (4) selection of endolysin candidates, and (5) evaluation of protein solubility. We then characterized the endolysin candidate under various conditions. Approximately 67% of S. aureus was detected as MRSA and a total of 114 putative endolysins were found. The 114 putative endolysins were divided into three groups based on their combination of conserved domains. Considering the protein solubility, we selected putative endolysins 177 and 117. Putative endolysin 117 was successfully overexpressed and renamed LyJH1892. LyJH1892 lysed approximately 85% of S. aureus. LyJH1892 showed more potent lytic activity against MRSA than normal S. aureus (relative lytic activity &gt; 125%). LyJH1892 showed broad lytic activity against coagulase-negative Staphylococci (CNS). In conclusion, These findings provide a rapid and useful strategy for the development of specific endolysins against antibiotic-resistant bacterial strains.

Abstract: Enfortumab vedotin (EV), an antibody-drug conjugate directed against Nectin-4, signif-icantly prolonged survival when compared with standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who previously received platinum-based chemo-therapy and a PD-1 or PD-L1 inhibitor. The confirmed overall response rate in the phase 3 EV301 trial leading to approval was 40.6%. However, no data have been published about the activity in brain metastases. Here, we present three patients from different centers with brain metastases receiving EV. A 58-year-old male Caucasian patient, who was heavily pretreated for urothelial carcinoma with visceral metastases and a solitary clinically active brain metastasis, started on EV 1.25 mg/kg on days 1, 8, and 15 of a 28-day cycle. The first evaluation after three cycles of EV showed a partial remission by RECIST v1.1 with a near complete response in the brain metastasis and disappear-ance of the neurological complaints. The patient is currently still receiving EV. A second, 74-year-old male patient started on the same regimen, after previous progression on platinum-based chemotherapy and maintenance avelumab. The patient achieved complete response and remained on therapy for five months. However, therapy was discontinued at the patient’s re-quest. Shortly after, he developed new leptomeningeal metastases. Upon rechallenge with EV, there was a significant reduction in the diffuse meningeal infiltration. A third, 50-year-old male Caucasian patient also received EV, after previous progression on cisplatin-gemcitabine and ate-zolizumab maintenance followed by palliative whole brain radiotherapy and two cycles of vin-flunine. The first evaluation after three cycles of EV showed a significant reduction of the brain metastases. The patient is currently still receiving EV. These are the first reports on efficacy of EV in patients with urothelial carcinoma and active brain metastases.

In celIs, microtubule location, length, and dynamics are regulated by a host of microtubule-associated proteins and enzymes that read where to bind and act based on the microtubule “tubulin code,” which is predominantly encoded in the tubulin carboxy-terminal tail (CTT). Katanin is a highly conserved AAA ATPase enzyme that binds to the tubulin CTTs to remove dimers and sever microtubules. We have previously demonstrated that short CTT peptides are able to inhibit katanin severing. Here, we examine effects of CTT sequences on this inhibition activity. Specifically, we examine CTT sequences found in nature, alpha1A (TUBA1A), detyrosinated alpha1A, Δ2 alpha1A, beta5 (TUBB/TUBB5), beta2a (TUBB2A), beta3 (TUBB3), and beta4b (TUBB4b). We find that these natural CTTs have distinct abilities to inhibit, most noticeably beta3 cannot inhibit katanin. Two non-native CTT tail constructs are also unable to inhibit – despite having 94% sequence identity with alpha1 or beta5 sequences. Surprisingly, we demonstrate that poly-E and poly-D peptides are capable of inhibiting katanin significantly. An analysis of the hydrophobicity of the CTT constructs indicates that more hydrophobic polypeptides are less inhibitory than more polar polypeptides. These experiments not only demonstrate inhibition, but also likely interaction and targeting of katanin to these various CTTs when they are part of a polymerized microtubule filament.

Cryptococcus neoformans is a multidrug-resistant human pathogenic yeast responsible for infections in immunocompromised patients. Here, Itraconazole (ITR), a commercial antifungal drug with low effectiveness against C. neoformans, was combined with different synthetic peptides Mo-CBP3-PepII, RcAlb-PepII, RcAlb-PepIII, PepGAT, and PepKAA. The mechanisms of action responsible for the synergistic effect were evaluated for the best combinations by Fluorescence Microscopy (FM). The synthetic peptides enhanced the activity of ITR by 10-fold against C. neoformans. Our results demonstrated that the combinations could induce pore formation in the membrane and overaccumulation of ROS on C. neoformans cells. Our findings indicate that our peptides successfully potentialize the activity of ITR by reducing it by 10-fold to reach antifungal activity against C. neoformans. Therefore, synthetic peptides are potential molecules to act as co-adjuvant agents in treating Cryptococcal infections.

It is urgent to find new antibiotic classes to replenish the empty development pipeline of antibiotics. Recently, pyrrolobenzodiazepines (PBDs) with a C8-linked aliphatic-heterocycle have been identified as a new broad spectrum antibiotic class with activity against Gram-negative bacteria. The active imine moiety of the reported lead pyrrolobenzodiazepine compounds was replaced with amide to obtain the non-DNA binding and non-cytotoxic dilactam analogues to further understand the structure activity relationship and improve the safety potential of this class. The synthesized compounds were tested against panels of multidrug resistant Gram-positive and Gram-negative bacteria, including WHO priority pathogens. Minimum inhibitory concentrations for the dilactam analogues ranged from 4 – 32 mg/L for MDR Gram-positive bacteria, compared to 0.03 to 2 mg/L for the corresponding imine analogues while they were found to be inactive against MDR Gram-negative bacteria, with an MIC &gt;32 mg/L, compared to an MIC of 0.5 to 32 mg/L. A molecular modelling study suggests the lack of imine functionality also affects the interaction of PBDs with DNA gyrase. This study suggests the presence of N10-C11 imine moiety is crucial for broad spectrum activity of pyrrolobenzodiazepines.

This study is follow-up of the steel shot transformation under the influence of environmental factors research (Lisin et al., 2022) and is the initial stage of investigating the iron behavior in soils during steel shot corrosion under a number of factors: the metallic lead in soils, atmospheric precipitation, excess organic matter. The results obtained show that corrosion of steel ammunition is a continuous process, including the formation of a poorly soluble rust crust on the surface of the steel and the mineralization of the metal until it is destroyed. As a result, the metal transformed into rust form, is a constant source of iron ions and dispersed rust particles migrating in soil waters and accumulating in soils. In addition, the aggregation of corrosion products of steel ammunition is the cause of a change in physical and mechanical properties of soils, which leads to a violation of the air and water migration regime of soils and an increase in surface runoff from the territories of shooting activity. The highest environmental risks are observed when steel ammunition is used on shooting areas where metallic lead intensifies steel shot corrosion rate, while the deposited steel shot activates the deterioration of previously encapsulated metal and — if steel and lead ammunition are used at the same time — slows down the encapsulation of newly deposited metallic lead, which catalyses the accumulation and migration of lead in environmental components.

This study reports a computational investigation on the antioxidant activity of five plant food benzoic acid derivatives, namely gallic acid (GA), para-hydroxybenzoic acid (PHBA), protocatechuic acid (PCA), syringic acid (SA), and vanillic acid (VA). Based on computed thermodynamics parameters, a detailed comparative debate is developed concerning their free radical scavenging activity in the gas phase and polar solutions (in water and methanol solvents). This discussion goes on to elucidate both the most preferred mechanism and the order of antioxidant activity for these molecules in each environment. Paradoxically, calculations using the harmonic oscillator model of aromaticity (HOMA) suggest that H abstraction radicals gain in stability as the central benzene ring loses in structural aromaticity. Finally, spin densities and fukui function f⁰ seem to be good indicators of the local reactivity of these compounds towards free radicals.

ABSTRACT. The immunotherapies, as a modern therapeutic approach, get an attention because of theirs’ promise to treat a large number of different medical disorders. Immunomodulation effects of low titres (10 HA/ml) of NDV (Newcastle Disease Virus) ZG1999HDS or La Sota were tested on TLT (Human macrophage cell line) bound to PBMC (Peripheral Blood Mononuclear Cells). During the immunomodulation, the amount of NO, H2O2, lysozym and induced antibacterial activity against Gram - positive bacteria (Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus mutants) and against Gram - negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Acinetobacter baumanii) were analysed. In addition, the cytokine secretion, IL-1α, IL-2, IL-4, GM-CSF, TNF-α, IFN-α and IFN-α were evaluated. Firstly, the TLT cells are activated through the NDV ZG1999HDS or La Sota binding, followed by the NO “burst” and H2O2 and lysozyme level increase. Secondly, after the binding to the TLT cells and interaction with the PBMCs, the decrease of GM-CSF, and an increase of TNF – α and IFN – γ were found. Simultaneously, the decrease of pro – inflammatory cytokine IFN-α and the differentially increase of IL-1α, IL-2 and IL-4 were recorded. During the induction of the antibacterial response, against Gram - positive bacteria (Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus mutants) the effect was one third higher with NDV ZG1999HDS compared to La Sota. Antibacterial response against Gram - negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Acinetobacter baumanii) was not so clear. In general, NDV ZG1999HDS or La Sota activated TLT cells, further bound to PBMC; the ZG1999HDS is stronger immunomodulator than La Sota.

Staphylococcus aureus can develop resistance by mutation, tranfection or biofilm formation. Resistance was induced in S. aureus by growth in sub-inhibitory concentrations of ciprofloxacin for 30 days. The ability of the antimicrobials to disrupt biofilms was determined using crystal violet and live/dead staining. Effects on the cell membranes of biofilm cells was evaluated by measuring release of dyes and ATP and nucleic acids. S. aureus did not develop resistance to the AMPs but resistance increased to ciprofloxacin by 128 times after 30 passages. Only peptides reduced biofilms of ciprofloxacin resistant cells. The antibiofilm effect of melimine with ciprofloxacin was more (27%) than with melimine alone at 1X MIC (p < 0.001). Similarly, at 1X MIC the combination of Mel4 and ciprofloxacin produced more (48%) biofilm disruption than Mel4 alone (p < 0.001). Combinations of either of the peptides with ciprofloxacin at 2X MIC released  66 nM ATP, more than either peptide alone (p  0.005). At 2X MIC, only melimine in combination with ciprofloxacin released DNA/RNA which was 3 times more than released by melimine alone (p = 0.043). These results suggest the potential use of melimine and Mel4 with conventional antibiotics for the treatments of S. aureus biofilms.

Quadruplex-interactive small molecules have a wide potential application, not only as drugs but also as sensors of quadruplexes structures. The purpose of this work is the synthesis of analogues of the bis-methylquinolinium-pyridine-2,6-dicarboxamide G4 ligand 360A, to identify relevant structure-activity relationships to apply to the design of other G4-interactive small molecules bearing bis-quinoline or bis-isoquinoline moieties. Thermal denaturation experiments revealed that non-methylated derivatives with a relative 1,4 position between the amide linker and the nitrogen of the quinoline ring are moderate G4 stabilizers, with a preference for the hybrid h-Telo G4. Insertion of a positive charge upon methylation of quinoline/isoquinoline nitrogen increases compounds capacity to selectively stabilize G4s compared to duplex DNA, with a preference for parallel structures. Among these, compounds having a relative 1,3-position between the charged methylquinolinium/isoquinolinium nitrogen and the amide linker are the best G4 stabilizers. More interestingly, these ligands showed different capacities to selectively block DNA polymer-ization in a PCR-stop assay and to induce G4 conformation switches of hybrid h-Telo G4. Mo-lecular dynamic simulations with the parallel k-RAS G4 structure showed that the relative spatial orientation of the two methylated quinoline/isoquinoline rings determines the ligands mode and strength of binding to G4s.

The estrogen hormone receptor (ER) mediated gene expression mainly regulate the development and physiology of primary and secondary reproductive system alongside bone-forming, metabolism and behaviour. Over-expressed ER is associated with several pathological conditions and play a key role in breast cancer occurrence, progression and metastasis. Hibiscus sabdariffa L. or roselle is a rich source of naturally occurring polyphenolic compounds including anthocyanins and reportedly have strong estrogenic activity. To validate these findings, we have investigated the estrogen receptor binding affinity and safety of some previously recorded polyphenols using a suite of computational methods. Our investigation showed the estrogen-receptor binding potential of Pelargonidin, Delphinidin, Cyanidin, and Hibiscetin are more efficient than popular breast cancer drugs, Tamoxifen and Raloxifene, with favourable toxicological parameters and low half maximal inhibitory concentration. This is the first report to investigate the phytochemical basis of estrogenic activity of Hibiscus sabdariffa L.

Background: Physical activity is recommended to mitigate the incidence of obesity, but delivery of community wide initiatives is cumbersome. The challenges met by such programs are magnified when implementation transpires in the remote villages of Alaska. To overcome the difficulty of this challenge in the Arctic, the Skiku/AK Nordic cross-country skiing program was developed. The objective of this study was to evaluate whether access to Skiku/AK Nordic program would promote physical activity levels that met the daily recommendations for physical activity in Alaska Native children. Methods: Eight children (4 females and 4 males; 10±2 years/age) were recruited from Kaktovik, Alaska for participation in this study. Expert coaches and staff provided one week of cross-country ski instruction and access to ski equipment. Physical activity was monitored using ActiGraph GT3X+ accelerometers. Data collected from the devices was then downloaded and analyzed using ActiLife software. Results: The participants expended ~586 calories/day devoted to physical activity. Light and moderate physical activity was 68±38 minutes/day and 447±248 minutes/day, respectively. Conclusions: Delivery of the Skiku/AK Nordic program promoted favorable levels of physical activity in Alaska Native children. Further research is needed to assess the longitudinal and seasonal effectiveness of the Skiku/AK Nordic program.

In this work, zinc oxide (ZnO) nanoparticles were modified in a circulating fluidized bed through argon and hydrogen (Ar-H) alternative-current (AC) arc plasma, which shows the characteristics of non-equilibrium and equilibrium plasma at the same time. In addition, a circulating fluidized bed with two plasma jets was used for cyclic processing. The catalytic degradation performance on Rhodamine B (Rh B) by Ar-H plasma modified ZnO and pure ZnO was tested in aqueous media to identify the significant role of hydrogen atoms in Rh B degradation mechanism. Meanwhile, the effects of plasma treatment time on the morphology, size and photocatalytic performance of ZnO were also investigated. The results demonstrated that ZnO after 20 minutes-treatment by Ar-H plasma showed Rh B photocatalytic degradation rate is ten times greater than that of pure ZnO, and the reaction follows a first-kinetics for the Rh B degradation process. Furthermore, the photocatalyst cycle experiment curve exhibited that the modified ZnO still displays optimum photocatalytic activity after five cycles of experiment. The improvement of photocatalytic activity and luminescence performance attributes to the significant increase of the surface area, and the introduction of hydrogen atoms on the surface also could enhance the time of carrier existence where the hydrogen atoms act as shallow donors.

Kinesio tape is considered one of the most common techniques which using recently, where it is used as a therapeutic technique for pain relief, correction of joint position, prevention of oedema and injuries, improve range of motion and muscular activity for the individual. This study is a descriptive research design and aims to identify the effect of using Kinesio tape on the neuromuscular activity of quadriceps muscle after the rehabilitation program of the knee joint. The study sample consists of (10) players from different sports (football, basketball …etc.) and suffering from knee joint injuries. This sample was taken from Kafr-El sheikh and Kaleen club. Results showed that Kinesio tape doesn’t have any explicit effect on the neuromuscular activity of muscle but acts as a catalyst for muscle and promote a person’s feeling of psychological wellbeing and reassurance.When comparing results of using Kinesio tape during performing leg squatting and balance test with not using tape, founded that when performing leg squatting and balance test with using Kinesio tape, there were significant effects on muscle activity compared to not using it.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that develops as a consequence of different factors such as oxidative stress and accumulation of the protein amyloid β (Aβ) in the brain, resulting in apoptosis of neuronal cells. The search for a treatment for this disorder is essential as current medications are limited to alleviating symptoms and palliative effects. The aim of this study is to investigate the effects of mint extracts on selected mechanisms implicated in the development of AD. To enable a thorough investigation of mechanisms, including effects on -secretase (the enzyme the leads to the formation of A), on Aβ aggregation, and on oxidative stress and apoptosis pathways, a neuronal cell model, SH-SY5Y cells was selected. Six Mentha taxa were investigated for their in vitro β-secretase (BACE) and Aβ-aggregation inhibition activities. Also, their neuroprotective effects on H2O2-induced oxidative stress and apoptosis in SH-SY5Y cells were evaluated through caspase activity. Real-time PCR and Western blot analysis were carried out for the two most promising extracts to determine their effects on signalling pathways in SH-SY5Y cells. All mint extracts had strong BACE inhibition activity. M. requienii extracts showed excellent inhibition of Aβ-aggregation, while other extracts showed moderate inhibition. M. diemenica and M. requienii extracts lowered caspase activity. Exposure of SH-SY5Y cells to M. diemenica extracts resulted in a decrease in the expression of pro-apoptotic protein, Bax, and an elevation in the anti-apoptotic protein, Bcl-xL, potentially mediated by down-regulation of ASK1-JNK pathway. These results indicate that mint extracts could prevent the formation of Aβ and also could prevent their aggregation if they had already formed. M. diemenica and M. requienii extracts have potential to suppress apoptosis at the cellular level. Hence, mint extracts could provide a source of efficacious compounds for a therapeutic approach for AD.

We examined how combinations of corporate social responsibility (CSR) activities lead to high performance in Korean companies. This study addressed two related questions to expand our limited knowledge in this area. The first was what combinations of CSR activities achieve high performance. The second was to identify how CSR activities form an interdependent system, depending on different corporate situations. Korean Economic Justice Institute index data, from 2012 to 2018, were used with fuzzy set qualitative comparative analysis, and the results revealed several effective CSR activity factor combinations under given strategies and management environments. Companies with high performance exhibit complementarity between social contribution, environmental management, fairness, and employee satisfaction. By contrast, companies with low corporate performance show no complementarity between relatively unrelated activity factors. For companies whose CSR activities lead to low financial performance, most of the causal pathways focused only on activities at the primary stakeholder level, with weak diversity of CSR activities’ combinations at the primary and secondary stakeholder levels. These results indicate not only the appropriateness of CSR activity factor combinations for companies’ strategy and management environment contexts, but also their effectiveness, and are expected to provide companies with significant implications for CSR activities.

Reducing carbohydrates digestion by having low glycaemic index (GI) foods has been linked to weight loss. Inhibiting related enzymes is an alternative way to decrease carbohydrate digestion. RCM-107, an eight-herb formula that is modified from the RCM-104, has indicated significant weight-loss action in clinical trials. However, no research has been conducted to study its effect on the activity of porcine pancreatic alpha-amylase (PPA), which is involved in carbohydrate absorption. In this paper, we used fluorescence PPA inhibition assay to investigate the inhibitory effects of RCM-107 and the individual herbs present in this herbal mixture on amylase activity. Subsequently, molecular docking predicted the key active compounds that may be responsible for the enzyme inhibition. According to our results, both the RCM-107 formula and several individual herbs displayed α-amylase inhibitory effects. Also, marginal synergistic effects of RCM-107 were also detected. In addition, alisol B, (-)-epigallocatechin-3-gallate (EGCG) and plantagoside have been predicted as the key active compounds that may be responsible for the α-amylase inhibition effect of RCM-107 according to inter-residue contact analysis. Finally, Glu233, Gln63, His305, Asp300 and Tyr151 are predicted to be markers of important areas with which potential amylase inhibitors would interact.

Background: Cancer stem cells (CSCs) exhibit self-renewal activity and give rise to other cell types in tumors. Due to the infinite proliferative potential of CSCs, drugs targeting these cells are necessary to completely inhibit cancer development. beta-lapachone (bL) has been widely used to treat cancer development, but its effect on cancer stem cells remain elusive. Thus, we investigated the effect of bL on mammosphere formation using breast cancer stem cell (BCSC) marker positive cells, MDA-MB-231. Methods: MDA-MB-231 Cells, which is negative for NQO1 expression, was constructed to stably express NQO1(NQO1 stable cells) to see the effect of bL. The effect of bL on cells were evaluated by wound healing and Transwell cell culture chambers, and ALDEFLUOR assay. Results: Here, we show that bL inhibited the proliferative ability of mammosphere derived from BCSC marker-positive cells, MDA-MB-231, in an NQO1-dependent manner. bL treatment efficiently downregulated expression level of BCSC markers CD44, ALDH1A1, and DLGAP5 that recently identified as a stem cell proliferation marker in both cultured cells and mammosphered cells. Moreover, bL efficiently downregulates cell proliferation and migration activities. Conclusions: These results strongly suggest that bL could be a therapeutic agent targeting breast cancer stem cells with proper NQO1 expression.

Bacterial resistance towards existing class of antibacterial drugs continues to increase posing significant threat to clinical usefulness of these drugs. This increasing and alarming rates of antibacterial resistance development and the decline in the number of new antibacterial drugs approval continue to serve as major impetus for research into discovery and development of new antibacterial agents. We synthesized a series D-/L-alaninyl substituted triazolyl oxazolidinone derivatives and evaluated their antibacterial activity against selected standard Gram-positive and Gram-negative bacterial strains. Overall, the compounds showed moderate to strong antibacterial activity. Compounds 9d and 10d (D- and L-alaninyl derivatives bearing 3,5-dinitrobenzoyl substituent), 10e (D-alaninyl derivative bearing 5-nitrofurancarbonyl group) and 9f and 10f (D- and L-alaninyl derivatives bearing 5-nitrothiophene carbonyl moiety) demonstrated antibacterial activity (MIC:2 g/mL) against S. aureus, S. epidermidis, E. faecalis and M. catarrhalis standard bacterial strains. No significant differences were noticeable between the antibacterial activity of the D- and L-alaninyl derivatives as a result of the stereochemistry of the compounds.

Background. A direct clinical and morphological comparison of non-COVID myocarditis than was diagnosed before the SARS-CoV-2 pandemic and post-COVID myocarditis has not been performed so far. Purpose: to compare morphological activity, toll-like receptors expression and response to the immunosuppressive therapy in patients with non-COVID and post-COVID myocarditis. Metodhs. Seventy-seven patients (52 male and 25 female, 48.7±11.7 y.o.) with biopsy proven myocarditis, NYHA class 2 or more heart failure, ejection fraction (EF) <45% were included. A history of myocardial infarction, verified cardiomyopathies, systemic autoimmune diseases, viral DNA in the myocardium, except parvovirus B19, were exclusion criteria. The right ventricular endomyocardial biopsy with hematoxylin and eosin, Van Gieson stains, PCR for virus (herpes viruses, parvovirus B19, adeno-, enteroviruses and SARS-CoV-2), immunohistochemical study for CD3, CD45, CD68, CD20, nucleocapsid / spike proteins of SARS-CoV-2 and in addition toll-like receptors (TLR) type 4 and 9 expression (in 38 patients) were performed. The steroids (methylprednisolone 24-40 mg per day), azathioprine, mycophenolate mofetil were prescribed. The mean follow-up was 16 [6; 30] month. Results. In 45 patients, myocarditis was diagnosed before the SARS-CoV-2 pandemic (giant-cell in one case and lymphocytic in the others). Other 32 patients had post-COVID myocarditis positive for RNA or/and proteins of SARS-CoV-2 (giant-cell in one case, eosinophilic in three cases and lymphocytic in the others). There were no differences in age, NYHA class, CRP and anti-heart antibodies level, echocardiographic parameters (mean EF 30.2±7.8 vs 28.7±6.7%), parvovirus B19 positivity (22 vs 34%), doses of methylprednisolone (24-40 mg/day) and death / transplantation rate (11.1 vs 9.4%). Differences between non-COVID vs post-COVID myocarditis focused on higher CD3, CD 45*, TLR 4 (4+ vs 6+), TLR 9 (0 vs 2+) expression and better response to therapy [10% or more increase in EF in 53 vs 86%* of patients, mean EF (43.9±12.3 vs 49.8±7.6%*) by the end of follow-up], *p<0.05. Conclusion. Post-COVID myocarditis is characterised by different morphological types, higher morphological activity, tendency to higher TLR expression and the best response to the immunosupressive therapy in comparison with non-COVID myocarditis.

Copper-containing materials are attracting attention as self-desinfecting surfaces, suitable for helping healthcare settings in reducing healthcare associated infections. However, the impact of repeated exposure to disinfectants frequently used in biocleaning protocols on their antibacterial activity remains insufficiently characterized. This study aimed at evaluating the antibacterial effi-ciency of copper (positive control), a brass alloy (AB+®) and stainless steel (negative control) after repeated exposure to a quaternary ammonium compound and/or a mix of peracetic acid/hydrogen peroxide routinely used in healthcare settings. A panel of 6 antibiotic-resistant strains (clinical isolates) was selected for this assessment. After a short (5 min) exposure time, the copper and brass materials retained significantly better antibacterial efficiencies than stainless steel, whatever the bacterial strain or disinfectant treatment considered. Moreover, post-treatment with both disinfectant products, copper-containing materials still reached similar levels of antibacterial efficiency as those obtained before treatment. Antibiotic resistance mechanisms such as efflux pump overexpression did not impair the antibacterial efficiency of copper-containing materials, neither did the presence of one or several genes related to copper homeostasis/resistance. In light of those results, surfaces made out of copper and brass remain interesting tools in the fight against dissemination of antibiotic-resistant strains that might cause healthcare associated infections.

Over the past thirty years, the red gorgonian Paramuricea clavata in the Mediterranean Sea has faced increasing threats, including heat waves and human activities such as fishing and diving. Epibiosis on damaged gorgonian colonies is generally used as an indirect indication of stressed conditions. The density and height of P. clavata and the percentage of colonies affected by epibiosis and entangled in lost fishing gear were studied to investigate the phenomenon and its trend over time in the Ligurian Sea. Analyses were based on transects collected during ROV campaigns between 2015 and 2022 at depths of 33-90 meters. A strong correlation was observed between fishing effort in the study area and the level of epibiosis. Maximal percentages of colonies affected by epibiosis and entanglement were recorded at depths of 50-70 meters. Temporally, marine heat waves before 2019 were identified as the primary cause of damage to P. clavata. The decrease in epibiosis percentages after 2019, despite the 2022 heat wave, may be due to a quick recovery ability of the populations and a reduction in fishing activities during the COVID-19 lockdown in 2020. Long-term monitoring programs are essential to understand the changes in marine benthic communities exposed to different stressors.

This paper proposes a heuristic approach for managing complex construction projects. The tool incorporates with Primavera P6 EPPM and Synchro 4D, enabling proactively clash detection and resolution of spatial conflicts during concurrent tasks. Additionally, it performs resource verification for sufficient allocation before task initiation. This integrated approach facilitates the generation of conflict-free and feasible construction schedules. By adhering to project constraints and seamlessly integrating with existing industry tools, the proposed solution offers a comprehensive and robust approach for construction project management. This constitutes to our knowledge the first dynamic digital twin for the delivery of a complex project.

. Background/Objectives: Crohn's disease is a chronic and debilitating intestinal disorder that alternates between remission and active flare-ups, often leading to hospitalization. Social support is known to enhance adaptation to the disease and modulate stress perception in patients, while stress may exacerbate symptoms. The aim of this study was to examine the roles of perceived stress and social support in Crohn's disease and their impact on the frequency of flare-ups. Methods: A cross-sectional observational study was conducted, assessing stress and social support in a cohort of 91 patients with Crohn's disease during flare-up and remission phases. The Perceived Stress Scale (PSS-14) and a Social Support Questionnaire were utilized for evaluation. We examined the relationship between stress and social support in Crohn's disease. The interaction between the variables studied was also studied, considering the stage of the disease. Finally, we realized analysis of the influence of these two variables on the development of flares in Crohn's disease. Results: The study revealed that patients experience higher stress levels during flare-ups and that these levels are amplified by a lack of social support. A significant relationship was identified between the levels of social support and the occurrence of flare-ups, indicating that better social support is associated with fewer flare-ups.. Conclusions: Patients with Crohn's disease in the flare-up phase are subject to considerable stress. Deficit in social support is linked to an increase in stress levels. The interplay of social support and stress plays a critical role in the development of flare-ups.

This study developed Makgeolli (Korean traditional alcoholic beverage) by adding raw 20% Codium fragile (Cf), a green seaweed, to a mixed base consisting of rice and oats (1:1 ratio) (COM) and analyzed its quality characteristics and antioxidant activity. The rice based Makgeolli supplemented with raw 20% Cf was designated as control (CRM). The physicochemical (pH, acidity), microbiological (yeast, lactic acid bacteria), antioxidant (DPPH, ABTS), and sensory properties (7-henodonic scale) of CRM and COM were investigated during 7 days of fermentation. The pH/acidity levels of CRM and COM reached 3.66/0.68 and 3.69/0.95 after 7 days of fermentation, respectively. Compared to CRM, COM had lower alcohol and sugar contents (P < 0.05) (CRM: 14.5%/9.8 Brix, COM: 11.2%/7.4 Brix). However, COM contained more yeast and lactic acid bacteria (P < 0.05) (CRM: 1.30/4.28 log, COM: 6.04/6.09 log) compared to CRM. The antioxidant activity of DPPH/ABTS (P < 0.05) in COM was approximately 1.5 times that of CRM (CRM: 40.00/51.57%, COM: 56.76/70.91%). In addition, COM had an excellent sensory preference score (P < 0.05) due to its overall fresh flavor and savory taste (CRM: 4.93, COM: 6.06). Therefore, COM was shown to be Makgeolli with enhanced antioxidant function, with yeast and lactic acid bacteria, and improved flavor, suggesting the possibility of commercializing this Makgeolli.

The new diprotic ligand 3,5-di-tert-butylsalicylaldehyde 4-ethyl-3-thiosemicarbazone, abbreviated H2(3,5-t-Bu2)-sal4eT, exists as the thio-keto tautomer and adopts the E-configuration with respect to the imine double bond as evidenced by single-crystal X-ray analysis and corroborated by spectroscopic characterisation. Upon treatment with Cu(OAc)2·H2O in the presence of either 2,9-dimethyl-1,10-phenanthroline (2,9-Me2-phen) or 1,10-phenanthroline (phen) as a co-ligand in MeOH, this thiosemicarbazone undergoes conformational transformation (relative donor-atom orientations: syn,anti → syn,syn) concomitantly with tautomerization and double deprotonation to afford the ternary copper(II) complexes [Cu{(3,5-t-Bu2)-sal4eT}(2,9-Me2-phen)] (1) and [Cu2{3,5-t-Bu2)-sal4eT}2(phen)] (2). Crystallographic elucidation has revealed that complex 1 is a centrosymmetric dimer of mononuclear copper(II) complex molecules brought about by intermolecular H-bonding. The coordination geometry at the copper(II) centre is best described as distorted square pyramidal in accord with the trigonality index (τ = 0.14). The co-ligand adopts an axial-equatorial coordination mode; hence there is a disparity between its two Cu–N coordinate bonds arising from weakening of the apical one as a consequence of the tetragonal distortion. The axial X-band ESR spectrum of complex 1 is consistent with retention of this structure in solution. Complex 2 is a centrosymmetric dimer of dinuclear copper(II) complex molecules exhibiting intermolecular H-bonding and π-π-stacking interactions. The two copper(II) centres, which are 4.8067(18) Å apart and bridged by the thio-enolate nitrogen of the quadridentate thiosemicarbazonate ligand, display two different coordination geometries, one distorted square planar (τ4 = 0.082) and the other distorted square pyramidal (τ5 = 0.33). Such dinuclear copper(II) thiosemicarbazone complexes, which are crystallographically characterised, are extremely rare. In vitro, complexes 1 and 2 outperform cisplatin as antiproliferative agents in terms of potency and selectivity towards HeLa and MCF-7 cancer cell lines.

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.

This work is based on identifying the analysis techniques used to evaluate the antioxidant and anti-inflammatory effects using the zebrafish model. In this context, a literature review was performed with the Web of Science database. We used the terms zebra fish, antioxidant, anti-inflammatory, model, and Danio rerio. Fifty articles were reviewed, of which thirty-three were chosen to perform this review and were classified according to the source of plant extracts, compounds extracted from plants, chemical compounds, and other sources. This paper is an effort to provide a literature review on zebrafish models and elucidate their pros and cons to evaluate anti-inflamatory and antioxidant activity.

This study aimed to verify the effects of an acute increase in blood pressure (BP) and/or renal sympathetic nerve activity (rSNA) on the renal excretion of sodium and water and its potential effect on the regulation of NHE3 activity. Uninephectomized anesthetized male Wistar rats were divided into three experimental groups: 1) Sham, the rats had their BP and rSNA recorded, and urine was collected for 2 h; 2) bicuculline (Bic) paraventricular nucleus of the hypothalamus (PVN), rat BP, and rSNA were recorded, and urine was collected for 1 h at baseline conditions and 1 h after bicuculline injection into the PVN; 3) RNS + Bicuculine injection into the PVN, BP, and rSNA were recorded, and urine was collected 1h after RNS and 1 h after bicuculline injection into the PVN. Renal nerve stimulation (RNS) decreased sodium and water excretion independent of changes in BP. However, after Bic in the PVN during RNS stimulation, BP and rSNA increased up to 30% and 60%, respectively, increasing diuresis (5-fold) and natriuresis (2.3-fold), accompanied by a significant reduction in the NHE3 activity independent of GFR changes. In conclusion, an acute increase in BP overcomes such effects, generating diuresis, natriuresis, and NHE3 activity inhibition.

The primary goal of this research is to examine the α-amylase inhibitory effect of phytoconstituents found in the roots of the Cyclea peltata plant. The extract will also be used to investigate the effect of root extract on α-amylase inhibition assay. The roots were gathered, processed, and extracted in petroleum ether before being kept at 4ºC. The extract was exposed to a preliminary phytochemical examination. The extract was employed in the α-amylase inhibition experiment at concentrations of 50, 100, 200, 400, 600, 800, and 1000 µg/ml with acarbose as a control. Molecular docking analysis was performed on the phytoconstituents cycleapeltine, cycleadrine, cycleacurine, cycleanorine, cycleahomine chloride, and acarbose on human pancreatic alpha-amylase 1B2Y. A preliminary phytochemical study revealed the presence of alkaloids, saponins, and terpenoids. The tests came back negative for flavonoids, steroids, and tannin. The root extract inhibited α-amylase at 69.42 ± 0.74 % at 1000 µg/ml and acarbose at 94.63 ± 0.57 %. The IC50 value was calculated and found to be 484.08 µg/ml for the extract and 42.47 µg/ml. The docking studies, revealed that cycleacurine (-4.751 Kcal/mol) has a comparable anti-diabetic effect to Acarbose (-6.713 Kcal/mol). Furthermore, the function groups –OH and –NH found in phytoconstituents interacted with the active site of 1B2Y similarly to acarbose. This provides evidence that the function groups –OH and –NH present in the phytoconstituents might inhibit alpha amylase.

Heparins, Unfractionated or Low Molecular Weight, are permanently at the spotlight of both clinical indications and laboratory monitoring. An accurate drug dosage is necessary for an effi-cient and safe therapy. The one-stage anti-FXa kinetics’ assays are the most widely and universally used with full automation for large series, without needing exogenous Antithrombin. WHO in-ternational standards are available for UFH and LMWH, but external quality assessment surveys still report a high inter-assay variability. This heterogeneity results from: assay formulation, designed without or with dextran sulfate to measure all heparin in blood circulation; calibrators for testing UFH or LMWH with the same curve; and automation parameters. The various factors which impact heparin measurements are reviewed, and we share our experience to optimize assays for completely testing plasma heparin. Evidence is provided on the usefulness of low molecular weight dextran sulfate to mobilize all drug present in blood circulation. Other key factors concern adjustment of assay conditions to obtain fully superimposable calibration curves for UFH and LMWH, and automation parameters. The study is illustrated by the performances of the various anti-FXa assays used for testing heparin on UFH or LMWH treated patients’ plasmas and obtained using citrate or CTAD anticoagulants. Comparable results are obtained only when CTAD anti-coagulant is used. Using citrate UFH is underestimated in the absence of dextran sulfate. Heparin calibrators, adjustment of automation parameters and data treatment contribute to other smaller differences.

The pregnane X receptor (PXR) is the main nuclear receptor regulating the expression of xenobiotic metabolizing enzymes and is highly expressed in the liver and intestine. Recent studies have highlighted its additional role in lipid homeostasis, however, the mechanisms of these regulations are not fully elucidated. We investigated the transcriptomic signature of PXR activation in the liver of adult wild-type vs Pxr-/- C57Bl6/J male mice treated with the rodent specific ligand pregnenolone 16α-carbonitrile (PCN). PXR activation increased liver triglyceride accumulation and significantly regulated the expression of 1215 genes mostly xenobiotic metabolizing enzymes. Among the down-regulated genes, we identified a strong peroxisome proliferator-activated receptor α (PPARα) signature. Comparison of this signature with a list of fasting-induced PPARα target genes confirmed that PXR activation decreased the expression of more than 25 PPARα target genes, among which the hepatokine fibroblast growth factor 21 (Fgf21). PXR activation abolished plasmatic levels of FGF21. We provide a comprehensive signature of PXR activation in the liver and identify new PXR target genes that might be involved in the steatogenic effect of PXR. Moreover, we show that PXR activation down-regulates hepatic PPARα activity and FGF21 circulation, which could participate in the pleiotropic role of PXR in energy homeostasis.

One of the richest natural sources of resveratrol - the rhizome of Reynoutria japonica in East Asia is a well-known traditional herb (Hu zhang) used in various inflammatory diseases, infections, skin diseases, scald, hyperlipidemia. Although, it has been recently included in the European Pharmacopoeia, still in Europe is an untapped resource. Some of the therapeutic effects are likely to be influenced by its antioxidant properties and this in turn is frequently associated with a high stilbene content. However, some literatures suggested that other compounds than stilbenes may add to the total antioxidant capacity. Hence, the aim of this research was to examine rhizomes of R. japonica and less studied, morphologically similar species, R. sachalinensis and R. x bohemica for their phytochemical composition and antioxidant activity and to clarify the relationship between the antioxidant activity and compounds by statistical methods. HPLC/UV/ESI-MS studies of three Reynoutria species revealed 171 compounds comprising stilbenes, carbohydrates, procyanidins, flavan-3-ols, anthraquinones, phenylpropanoids, lignin oligomers, hydroxycinnamic acids, naphthalenes and their derivatives. Our studies confirmed the presence of procyanidins with high degree of polymerization, up to decamers in the rhizomes of R. japonica and brings new data on the presence of these compounds in other Reynoutria species. A procyanidin trimer digallate was described for the first time in the studied plants. Moreover, we suggested a presence of new for these species, dianthrone glycosides and previously unrecorded phenylpropanoid disaccharide esters and hydroxycinnamic acid derivatives, mainly in R. sachalinensis. Furthemore, compounds tentatively annotated as lignin oligomers were observed for the first time in studied species. The rhizomes of all Reynoutria species exhibited strong antioxidant activity. Statistical analysis demonstrated that proanthocyanidins should be considered as important contributors to the total antioxidant capacity.

Information can be considered as the most fundamental, philosophical, physical and mathematical concept originating from the totality by means of physical and mathematical transcendentalism (the counterpart of philosophical transcendentalism). Classical and quantum information, particularly by their units, bit and qubit, correspond and unify the finite and infinite. As classical information is relevant to finite series and sets, as quantum information, to infinite ones. A fundamental joint relativity of the finite and infinite, of the external and internal is to be investigated. The corresponding invariance is able to define physical action and its quantity only on the basis of information and especially: on the relativity of classical and quantum information. The concept of transcendental time, an epoché in relation to the direction of time arrow can be defined. Its correlate is that information invariant to the finite and infinite, therefore unifying both classical and quantum information.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.

Geopolymer concrete (GPC) represents an innovative green and low-carbon construction material, offering a viable alternative to ordinary Portland cement concrete in building applications. However, existing studies tend to overlook the recyclability aspect of GPC for future use. Various structural applications necessitate the use of concrete with distinct strength characteristics. The recyclability of the parent concrete is influenced by these varying strengths. This study examined the recycling potential of GPC across a spectrum of strength grades (40, 60, 80 and 100 MPa, marked as C40, C60, C80 and C100) when subjected to freeze-thaw conditions. The cementitious material comprised 60% metakaolin and 40% slag, with natural gravel serving as the coarse aggregate, and the alkali activator consisting of sodium hydroxide solution and sodium silicate solution. The strength of the GPC was modulated by altering the Na/Al ratio. After 350 freeze-thaw cycles, the GPC specimens underwent crushing, washing, and sieving to produce recycled geopolymer aggregates (RGAs). Subsequently, their physical properties and microstructure were thoroughly examined. The findings indicated that GPC with strength grades of C100, C80, and C60 were capable of enduring 350 freeze-thaw cycles, in contrast to C40, which did not withstand these conditions. RGAs derived from GPC of strength grades C100 and C80 complied with the criteria for Class II recycled aggregates, whereas RGAs produced from GPC of strength grade C60 aligned with the Class III level. A higher strength grade in the parent concrete correlated with enhanced performance characteristics in the resulting recycled aggregates.

Background: Early rehabilitation is an important strategy for the treatment of severe diseases. The study aimed to assess the efficacy of early rehabilitation of patients with mild-to-moderate COVID-19. Methods: The retrospective single-center study with propensity score matching. Results: 180 patients (54 (44 - 62.3) yo) divided into three equal groups: 1 - physical exercises; 2 - physical exercises and chest massage in an electrostatic field; 3 - no rehabilitation. The length of stay (LOS) in the hospital in group 1 was 14 (11-15) days, group 2 - 13 (11-15) days, group 3 - 15 (13-18) days, p=0.0026. Physical exercises for patients with CT-1 improved the quality of life, assessed by the EQ-5D questionnaire, by reducing the level of anxiety and depression. The Hazard Ratio (HR) for desaturation (<93%) was 2.34 (95% Confidence Interval (CI) 1.18-4.63) for group 2, p=0.001. The HR for C-reactive protein level above 50 mg/l in patients with CT-2 was 2.33 (95% CI 1.56-3.47), p=0.0001. Conclusions: Rehabilitation programs are safe for СOVID-19-patients; reduce hospital LOS; improve the quality of life. Continuous monitoring of a patient's condition during rehabilitation is essential. ClinicalTrials.gov ID: NCT0580836

Introduction: When analyzing the current situation in Spain, derived from our current lifestyles far from following a Mediterranean lifestyle, there is an alarming prevalence of diabesity, which increases the global risk of suffering from cardiovascular disease (CVD) and decreases the quality of life related to health (QLRH). In order to guarantee, beyond glycemic control of patients with type 2 diabetes (DM2), adequate control of cardiovascular risk factors (CVRF) in DM2, it will be necessary to carry out a community intervention focused on the application of education programs focused on promoting the acquisition of healthy eating habits through the Mediterranean diet (DMED). This dietary pattern, together with physical exercise, has been shown to contribute to improving the QLRH of patients. Objective: To analyze the quality of life related to health, present in patients with poorly controlled type 2 diabetes, to determine the possible relationship between this and the degree of adherence to the Mediterranean diet and to examine whether there are differences between the sexes. Material and methods: Observational descriptive study in 93 patients diagnosed with DM2 with poor glycemic control (1Ac ≥ 7%), carried out in various health centers in Albacete and Cuenca, in which the baseline relationship between adherence to DMed and the HRQoL. They were administered a data collection sheet that included a survey of the degree of adherence to the DMed (MEDAS-14) and QLRH (SF-12v2) in the Primary Care (PC) medical and nursing consultations. The variables were analyzed: age groups, sex, years of evolution of DM2, body mass index (BMI), as well as basal glycemia (GB) and glycosylated hemoglobin (HbA1c). The “MEDAS-14” (adherence to DMED) was the main variable and the “SF-12v2” (QLRH) was the secondary variable. Material and methods: Observational descriptive study in 93 patients diagnosed with DM2 with poor glycemic control (1Ac ≥ 7%), carried out in various health centers in Albacete and Cuenca, in which the baseline relationship between adherence to DMed and the HRQoL. They were administered a data collection sheet that included a survey of the degree of adherence to the DMed (MEDAS-14) and QLRH (SF-12v2) in the Primary Care (PC) medical and nursing consultations. The variables were analyzed: age groups, sex, years of evolution of DM2, body mass index (BMI), as well as basal glycemia (GB) and glycosylated hemoglobin (HbA1c). The “MEDAS-14” (adherence to DMED) was the main variable and the “SF-12v2” (QLRH) was the secondary variable. Results: Patients with poorly controlled DM2 and with low adherence to the MedDM show a non-significantly greater affectation in the physical sphere: fair general state of health, physical function I (limitation to make moderate efforts such as moving a table, vacuuming or walk more than an hour), physical function II (limitation to climb several flights of stairs), physical role (problems at work or daily activities doing less than loved ones), physical role II (they had to stop performing some tasks at work or activities of daily living) and regular body pain. Presenting less affectation in the mental field: emotional role I, emotional role II, mental health I, vitality and mental health II. Without affectation in the social function since they consider that rarely the emotional or physical problems have hindered their social activities. Conclusions: Diabetic patients with poor glycemic control have low adherence to the MedMD (<9 points) and have poor QLRH. Low adherence to the DMed and obesity are related to a greater affectation in the physical dimension and less affectation in the mental dimension without affectation in the "social function".

Knee Osteoarthritis (KOA), the most common knee degenerative disease, involve a slow destructive process, leading to disability and ultimately total knee replacement. The progression of KOA is related to the loss of rheological properties of the synovial fluid (SF), due to slow immunological, inflammatory and enzymatic processes that cleave the hyaluronic acid (HA) and decrease the concentration of specific proteins. Since no effective treatments have been found to halt the progression of KOA, injection of HA-based viscoelastic gels combined with physiotherapy (PT) is an alternative to symptomatic therapies. In order to evaluate the effect of viscosupplementation and PT on the SF characteristics, the SF aspirated from the KOA was spectrophotometrically and rheological analyzed, comparing the receiving groups of HA Kombihylan® and groups that received Kombihylan® and complex PT. In patients treated with PT, SF extracted 6 weeks after viscosupplementation had a superior elastic moduli (G') and viscous moduli (G") profile behavior, having a homogeneous distribution of proteins and polysaccharides in the SF, stimulating stronger interactions. In the absence of PT the G' and G" profiles are non-uniform, suggesting an unorganized supplemented SF with some clustering phenomena, proteins aggregation and a low level of entanglement between HA and macromolecular components in the SF.

Despite the well-documented health benefits of recreational sports, few opportunities exist in lower- and middle-income countries for adult women to participate in recreational physical activities. An explanatory sequential mixed methods approach was used to explore associations between an innovative soccer program for adult women and self-reported health status. Cross-sectional survey data were collected in 2018-2019 from 702 women in the Nikumbuke Project, a health and literacy program in southeastern rural Kenya, followed by focus group discussions with 225 women who also participated in the Project's soccer program. Quantitative findings suggest that women who participated in soccer had 67% greater odds of reporting good or excellent health than their non-soccer playing peers. Thematic analysis of qualitative data indicated that women credited soccer with less pain, fatigue, and stress, as well as weight loss and reduced dependence on medicine for hypertension, pain, and sleep problems. Women equated health benefits with greater ease and efficiency in completing chores, reduced worries, youthful energy, male-like strength, and pleased husbands. Soccer programs for adult women may be particularly effective interventions in settings where access to health care is limited and where lack of opportunity to engage in physical aerobic activity increases women's risks for poor health outcomes. .

Digital enabled manufacturing systems require high level of automation for fast and low-cost production but should also present flexibility and adaptiveness to varying and dynamic conditions in their environment, including the presence of human beings; However, this presence of workers in the shared workspace with robots decreases the productivity as the robot is not aware about the human position and intention which leads to concerns about the human safety. This issue is addressed in this work by designing a reliable safety monitoring system for collaborative robots (Cobots). The main idea here is, to significantly enhance safety by a combination of recognition of human actions using visual perception and at the same time interpreting physical human-robot contact by tactile perception. Two datasets containing contact and vision data are collected by using different volunteers. The action recognition system classifies human actions using the skeleton representation of the latter when entering the shared workspace and the contact detection system distinguishes between intentional and incidental interactions if a physical contact between human and cobot takes place. Two different deep learning networks are used for human action recognition and contact detection which in combination, are expected to lead to the enhancement of human safety and an increase of the level of cobot perception about human intentions. The results show a promising path for future AI-driven solutions in safe and productive human–robot collaboration (HRC) in industrial automation.

Planck’s constant and the gravitational constant are comprised of more fundamental quantities of length, mass, and time. Reformulating traditional equations in terms of these fundamental units offers a more granular view of the physical transformations encoded in the equations of physics. The composite structure of h and G conceals a simple model in which maximum unit potentials are reduced by dimensionless proportionality operators. Natural symmetries correlate the three unit dimensions, yielding predictable quantities of physical dynamics. Insights are organized into a New Foundations Model of physics that reformulates traditional constants and equations in elementary form. The New Foundations Model offers a common language for describing quantum mechanical, gravitational, and electromagnetic phenomena.

In this study, Li-Al-OH layered double hydroxide (LDH), which was prepared by solvent-free one-step mechanochemical reaction of LiOH and Al(OH)₃, was applied to remove boron from aqueous solution. Dry-grinding for 3 h at a rotational speed of 500 rpm, Li/Al molar 1/2 was the optimum condition to prepare highly crystalline of Li-Al LDH phase with no evident impure phases. Two milling products with Li/Al molar ratio at 1/2 and 2/2 were evaluated for boron adsorption. The results confirmed that Li/Al molar ratio 2/2 sample showed high boron adsorption capacity due to the physical adsorption of Li-Al-OH LDH and chemical synergism of phase gel Al(OH)₃. The adsorption isotherms, described by the Langmuir model, indicated maximum monolayer boron uptake capacity 45.45 mg/g, implying competitive adsorption capacity of the material in our experiment.

This work reports measurements of calcified gallstone elemental compositions using laser-induced optical emission spectroscopy. The experimental results support the importance of the magnesium concentration in gallstone growth. Granular stones reveal an increased magnesium concentration at the periphery of the granules, suggesting the inhibition of further growth. Non-granular gallstones reveal lower overall magnesium concentrations but with higher values near the center.

Strata and surface movement induced by mining under open-pit final slope is a huge threat to mine safety. Physical model test is an important method to study mining-induced strata and surface movement laws. Because of rock joints predominantly control rock mass deformation and failure, thus physical model test leaving out of consideration of rock joints is difficult to reflect the influence of rock joints on rock mass deformation. Therefore, this paper presents a three-dimensional physical model test considering simplified dominant rock joints. This test process includes the design of testing equipment, the construction of physical model with dominant rock joint sets, conduction of mining and deformation monitoring. And mining under eastern final slope of Yanqianshan iron mine was selected as a case to study the behavior of mining-induced strata and surface movement.

Highly flexible manufacturing systems require continuous run-time (self-) optimization of processes with respect to various parameters, e.g. efficiency, availability, energy consumption etc. A promising approach for achieving (self-) optimization in manufacturing systems is the usage of the context sensitivity approach. Thereby the Cyber-Physical Systems play an important role as sources of information to achieve context sensitivity. In this paper it is demonstrated how context sensitivity can be used to realize a holistic solution for (self-) optimization of discrete flexible manufacturing systems, by making use of Cyber-Physical System integrated in manufacturing systems/processes. A generic approach for context sensitivity, based on self-learning algorithms, is proposed aiming at a various manufacturing systems. The new solution is propos encompassing run-time context extractor and optimizer. Based on the self-learning module both context extraction and optimizer are continuously learning and improving their performance. The solution is following Service Oriented Architecture principles. The generic solution is developed and then applied to two very different manufacturing processes. This paper proposes a holistic solution to achieve context sensitivity for Flexible Manufacturing Systems, whereby the knowledge created by applying the context sensitivity approach can be used for (self-) optimization of manufacturing processes.

The impact of interaction SS with MJO on rainfall along Java Island to East Nusa Tenggara has been studied using daily rainfall observation data from 2140 weather observation stations, which are also equipped with GSMaP, OLR, and ERA5 data. There were 61 SS events found, 17 during active MJO and 44 in inactive MJO. Rainfall increases more in the western study area when the active MJO and more in the eastern study area when the inactive MJO is due to SS. SS reduces rainfall in the Jakarta region, regardless of the activity or inactivity of the MJO. SS causes extreme rainfall to only occur in a small part of certain areas, so it tends to significantly reduce the possibility of extreme rainfall. In the southern part of the IMC, SS predominates over MJO in supporting increased water vapor transport. Large-scale synoptic circulations like the monsoon, SS, and MJO can interact with local land-sea wind circulation to produce spatiotemporal variability in rainfall on Java Island. Rainfall mostly increases in the afternoon and decreases in the morning when SS occurs, whether there is MJO or not. Convective instability analysis indicates that SS increases precipitation, most likely by lowering CIN and raising VIMFC.