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

Eysenhardtia platycarpa (Fabaceae) is a medicinal plant used in México and it lacks biotechnological studies for its use. The aim of this work was to establish a cell suspension cultures (CSC) of E. platycarpa, determine the phytochemical profile, and evaluate its antifungal activity. Friable callus and CSC were established with 2 mg/L 1-naphthaleneacetic acid plus 0.1 mg/L kinetin. The highest total phenolics of CSC was 15.6 mg GAE/g dry weight and the total flavonoids content ranged from 56.2 to 104.1 µg QE/g dry weight. CG‒MS analysis showed that the dichloromethane extracts of CSC, sapwood and heartwood have a high amount of hexadecanoic acid (22.3 ‒ 35.3 %) and steroids (13.5 ‒ 14.7%). Heartwood and sapwood defatted hexane extracts have the highest amount of stigmasterol (≈ 23.4%) and β-sitosterol (≈ 43%), and leaf extracts presented β-amyrin (16.3%). Methanolic leaves extracts showed mostly sugars and some polyols, mainly D-pinitol (74.3%). Dichloromethane and fatty hexane extracts of CSC exhibited the percentages inhibition higher for Sclerotium cepivorum with 71.5 and 62.0%, respectively. The maximum inhibition for Rhizoctonia solani was with fatty hexane extracts of the sapwood (51.4%). Our study suggest that CSC extracts could be used as a possible complementary alternative to synthetic fungicides.

Human eye is a specialized organ with complex anatomy and physiology, because it is characterized by different cell types with specific physiological functions. Given the complexity of the eye, ocular tissues are finely organized and orchestrated. In the last few years many in vitro models have been developed, in order to meet the 3Rs principle (Replacement, Reduction and Refinement) for eye toxicity testing. This procedure is highly necessary to ensure that the risks associated with ophthalmic products meet appropriate safety criteria. In vitro preclinical testing is now a well-established practice of significant importance for evaluating the efficacy and safety of cosmetic, pharmaceutical, and nutraceutical products. Along with in vitro testing, also computational procedures, herein described, for evaluating the pharmacological profile of potential ocular drug candidates including their toxicity, are in rapid expansion. In this review the ocular cell types and functionality are described providing an overview about the scientific challenge for the development of three-dimensional in vitro models.

There is a growing need for novel in vitro corneal models to replace animal-based ex vivo test in drug permeability studies. In this study we demonstrate a corneal mimetic that models the stromal and epithelial compartments of human cornea. Human corneal epithelial cells (HCE-T) were grown on top of a self-supporting porcine collagen-based hydrogel. Cross sections of the multilayers were characterized by histological staining and immunocytochemistry of zonula occludens-1 protein (ZO-1) and occludin. Furthermore, water content and elastic properties of the synthetized collagen type I-based hydrogels were measured. The apparent permeability coefficient (Papp) values of a representative set of ophthalmic drugs were measured and correlated to rabbit cornea Papp values found in the literature. Multilayered structure of HCE-T cells and expression of ZO-1 and occludin in full thickness of multilayer were observed. The hydrogel-based corneal model exhibited excellent correlation to rabbit corneal permeability (r=0.96), whereas insert-grown HCE-T multilayer was more permeable and the correlation to the rabbit corneal permeability was lower (r=0.89). The hydrogel-based human corneal model predicts the rabbit corneal permeability more reliably in comparison to HCE-T cells grown in inserts. This in vitro human corneal model can be successfully employed for drug permeability tests whilst avoiding ethical issues and reducing costs.

Leishmaniasis is a vector-borne parasitic infection caused by the bite of female Phlebotomine sandflies. World Health Organization (WHO) estimates 100,000 cases to be reported annually on a global scale, moreover, 13 million people were infected between 2010 and 2015 worldwide. Treatment of leishmaniasis by conventional synthetic compounds is met by challenges pertaining to adverse effects which call for the discovery of newer anti-leishmanial molecules. This study was performed to evaluate the effect and modes of action of a sesquiterpene alcoholic molecule Farnesol on Leishmania major, the causative agent of Zoonotic Cutaneous leishmaniasis. The cytotoxic effect of Farnesol against L. major promastigotes, amastigotes and macrophages was assessed by MTT test and counting. The IC50 on promastigotes by Farnesol on L. major was evaluated by flow cytometry. In the findings, Promastigotes were reduced at 167 µM/mL & the mean numbers of L. major amastigotes in macrophages were significantly decreased in exposure to Farnesol at 172 µM/ml. In addition, Farnesol demonstrated no cytotoxicity on macrophages as the IC50 value was 945 µM/ml; it induced significant apoptosis dose-dependent on L. major promastigotes. In silico protein-ligand binding analyses indicated the effect of Farnesol in perturbation of the ergosterol synthesis pathway of Leishmania with attributes suggesting inhibition of Lanosterol-α-demethylase, the terminal enzyme of ergosterol synthesis machinery. Findings from flow cytometry reveal the role of farnesol in apoptosis-induced killing in promastigotes. Farnesol was effective at very lower concentrations when compared to Paromomycin. Further studies are crucial to evaluate the therapeutic potentials of Farnesol alone and in combination with other conventional drugs using clinical settings.

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

Bacillus Calmette-Guérin (BCG) vaccine is the only licensed vaccine against tuberculosis (TB) in humans and animals. It is most commonly administered parenterally but oral delivery is highly advantageous for immunisation of cattle and wildlife hosts of TB in particular. Since BCG is susceptible to inactivation in the gut, vaccine formulations were prepared from suspensions of Eudragit L100 copolymer powder and BCG in PBS, containing Tween 80, with and without the addition of mannitol or trehalose. Samples were frozen at -20oC, freeze-dried and the lyophilised powders were compressed to produce BCG-Eudragit matrices. Production of the dried powders resulted in a reduction in BCG viability. Substantial losses in viability occurred at the initial formulation stage and at the stage of powder compaction. Data indicated that the Eudragit matrix protected BCG against simulated gastric fluid (SGF). The matrices remained intact in SGF and dissolved completely in SIF within three hours. The inclusion of mannitol or trehalose in the matrix provided additional protection to BCG during freeze-drying. Control needs to be exercised over BCG aggregation, freeze-drying and powder compaction conditions to minimise physical damage of the bacterial cell wall and maximise the viability of oral BCG vaccines prepared by dry powder compaction.

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated in the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interaction of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review we present different models that have been implemented in the fungal infections study with greater attention in Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host-microbe interactions. This is due to the fact that these systems have shown to have reliable results, which correlate with those obtained from mammalian models. Example of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.

Information on the nutritive value and in vitro fermentation characteristics of native shrubs in New Zealand is scant. This is despite their potential as alternatives to exotic trees and shrubs for sup-plementary fodder, and mitigation of greenhouse gas and soil erosion on hill country sheep and beef farms. The objectives of this study were to measure the in vitro fermentation gas production, predict parameters of in vitro fermentation kinetics and to estimate in vitro fermentation of volatile fatty acids (VFA), microbial biomass (MBM) and greenhouse gases of four native shrubs (Coprosma robusta, Griselinia littoralis, Hoheria populnea and Pittosporum crassifolium) and an exotic fodder tree species, Salix schwerinii. Total in vitro gas production was higher (p<0.05) for natives than S. schwerinii. Prediction using the single pool model resulted in biologically incorrect negative in vitro total gas production from the immediately soluble fraction of the native shrubs. However, the dual pool model better predicted in vitro total gas production and was in alignment with measured in vitro fermentation end products. In vitro VFA and greenhouse gas production from fermentation of leaf and stem material were higher (p<0.05), and MBM lower (p<0.05), for native shrubs com-pared to S. schwerinii. The lower in vitro total gas production, VFA and greenhouse gases produc-tion, and higher MBM of S. schwerinii may be explained by the presence of condensed tannins (CT), although this was not measured and requires further study. In conclusion, results from this study suggests that when consumed by ruminant livestock, the browsable native shrubs can provide adequate energy and microbial protein, and that greenhouse gas production from these species is within ranges reported for typical New Zealand pastures.

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

The poor success rate of preclinical drugs which target the nervous system is related to the highly complex nature of brain physiology and pathophysiology. For in vitro drug screening in this field, the two-dimensional (2D) approach - where cells are incubated in a monolayer - is not physiologically relevant. In contrast, in vivo rodent models are very low throughput and expensive. As such, improved, well-characterised three dimensional (3D) in vitro models should be employed to bridge the gap between 2D in vitro primary screening and rodent models by incorporating aspects of the in vivo brain environment. These key features include the extracellular matrix (ECM) and a multidimensional relationship of supporting cells. In this study, a neural progenitor cell line was differentiated into the main types of cells found in brain, including neurons and astrocytes. This model was designed in a 3D extracellular matrix replacement in a minimalised manner. Different culture formats using multi-well plates were explored and a high-throughput cellular imaging platform was applied. Next, we applied this model to assess neural toxicity of a newly synthesised dual-specificity tyrosine-regulated kinase 1 (DYRK1) inhibitor derived from natural compounds, which is structurally related to a natural DYRK1A inhibitor harmine, K04179. Chemical studies have already shown that K04179 has higher specificity to DYRK1A compared with previously reported DYRK1 inhibitors, such as INDY. We have produced the first report of the biological effects of this new compound on the new 3D minimalised mid-brain model with quantification of both neuronal and astrocyte populations in tandem, revealing differential toxic effects of DYRK1 inhibitor compounds K04179 and INDY on neurons and glia.

The inhibition of alpha-glucosidase and alpha-amylase is one of clinic strategies for remedy the type II diabetes. Herbal medicines are reported to alleviate hyperglycemia. However, the constituents from those sources whether are targeted to the alpha-glucosidase and alpha-amylase still unexplored. This study attempted to select the compounds for efficacy of hypoglycemia via cellular and mouse levels. The results illustrated that the cytotoxicity in all tested compounds at various concentrations except the concentration of 16-hydroxy-cleroda-3,13-dine-16,15-olide (HCD) at 30 µM were not significant difference (p > 0.05) when compared with the untreated control. Acarbose (reference drug), Antroquinonol, Catechin, Quercetin, Actinodaphnine, Curcumin, HCD, Docosanol, Tetracosanol, Berberine, and Rutin could effectively inhibit the alpha-glucosidase activity of Caco-2 cells when compared with the control (maltose). The compounds (Curcumin, HCD, Tetracosanol, Antroquinonol, Berberine, Catechin, Actinodaphnine, and Rutin) could reduce blood sugar level at 30 min in tested mice. The effects of tested compounds on area under curve (AUC) were significant (p < 0.05) among Acarbose, Tetracosanol, Antroquinonol, Catechin, Actinodaphnine, and Rutin along with Berberine and Quercetin. In in vitro (alpha-glucosidase) with in vivo (alpha-amylase) experiments suggest that bioactive compounds can be a potential inhibitor candidate of alpha-glucosidase and alpha-amylase for the alleviation of type II diabetes.

The majority of skin cancers are caused by over exposure to ultraviolet (UV) radiation. The effects of UV radiation on the expression of drug transporters expressed in human skin has never been studied. In this the effects of UVA and UVB irradiation on the expression of ATP-binding cassette (ABC) transporters and Solute carrier (SLC) transporters was evaluated in normal human epidermal keratinocytes (NHEK) and normal human dermal fibroblasts (NHDF) in primary culture. First experiments were intended to validate the inflammatory reaction in response to stimulation by lipopolysaccharide (LPS) in NHEK, NHDF and 3D-reconstructed human epidermis (3D-RHE) model. LPS treatment has shown to increase the expression of IL-8 and TNF-alpha in all three in vitro models. Expression of the most expressed ABC and SLC transporters was then measured in NHEK and NHDF after UVA (30 J/m²) and UVB (40 mJ/m²) irradiation. The most striking result was a significant 29-fold increase of the expression of SLCO4A1 in normal human dermal fibroblasts. In summary, this study shows for the first time a significant regulation of the expression of SLCO4A1 in human dermal fibroblasts induced by UVA irradiation. This finding is of particular interest as most of skin cancers are caused by over exposure to ultraviolet radiation and need to be considered in pharmacokinetic evaluation of topical drugs.

Peatlands in Indonesia are one of the world's largest carbon sinks, helping to regulate greenhouse gas emissions and global climate change. Lophostemon suaveolens is a plant found in Papua's endemic peat ecosystem that grows well in wet areas with low fertility. It is geographically dispersed and has the potential for peatland re-habilitation. We present an efficient and reproducible protocol for in vitro multiplication of plantlets using nodal segments and shoot apices collected from plantlets. The Murashige and Skoog (MS) medium was sup-plemented with single and double kinds of PGRs (BAP and NAA). The concentration used in this study is based on the best findings of earlier preliminary research on single PGR treatment (0.5 ml/l BAP and 0.1 ml/l NAA) for the initiation stage. After 3 months of in vitro axillary shoot initiation, elongated shoots from plant-lets were separated from the clumps and multiplied. Until 6 months incubation, the potential multiplication of axillary shoots was determined by counting the number of nodule multiplication coefficients (NMC), shoot length, root length, and number of leaves (6 successive subculture). The highest average per plantlet of NMC (8.4 0.13) was observed in MS medium with a combination of 0.5 ml/l BAP and 0.1 ml/l NAA (double PGRs), with the longest shoots (5.91 0.17 cm), the longest root length (8.83 0.69 cm), and the most leaves (32 0.69). They were cultured in a pH 5 environment with a light photoperiod (40 mol/m2/s intensity) for 16 hours. When BAP and NAA were used together after acclimatization, seedling survival was highest. This is the first report of L. suaveolens in vitro multiplication, and the protocol could be used to propagate this peatland species on a large scale.

Endotoxins are toxic substances that widely exist in the environment and can enter the intestine with food and other substances. Intestinal epithelial cells are protected by a mucus layer that contains MUC2 as its main structural component. However, a detailed understanding of the mechanisms involved in the function of the mucus barrier in endotoxin penetration is lacking. Here, we established the most suitable proportion of Caco-2/HT-29 co-culture cells as a powerful tool to evaluate the intestinal mucus layer. Our findings significantly advance current knowledge as focal adhesion and ECM-receptor interaction were identified as the two most significantly implicated pathways in MUC2 small interfering RNA (siRNA)-transfected Caco-2/HT-29 co-culture cells after 24 h of LPS stimulation. When the mucus layer was not intact, LPS was found to damage the tight junctions of Caco-2/HT29 co-cultured cells. Furthermore, LPS was demonstrated to inhibit the integrin-mediated focal adhesion structure and damage the matrix network structure of the extracellular and actin microfilament skeletons. Ultimately, LPS inhibited the interactive communication between the extracellular matrix and the cytoskeleton for 24 h in the siMUC2 group compared with the LPS(+) and LPS(-) groups. Overall, we recognized the potential of MUC2 as a tool for barrier function in several intestinal bacterial diseases.

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

Lily–belong to the genus Lilium is one of the top cut flowers worldwide. Production and propagation of bulblets in vitro is an important approach for high-volume production, but not proved satisfactory. Hence, the aim of this study was to describe and compare the performances of morphological characteristics of the lily bulb in vivo produced by in vitro and conventional culture method and compare the production timelines in vitro vs conventional culture method. In results, it seems clear that in vitro re-culture of lily bulblet was able to be sustained and maintained its growth and so, ontogenic development after their performance in soil. Our results demonstrate that in the conventional pathway, the course of bulblet growth to bulb and ontogenic development took 3–4 growing seasons to reach the adult flowering phase. On the other hand, along with the re-culture in vitro, the course of bulb growth and ontogenic development took 1–2 growing seasons to reach the adult flowering phase because of the increasing initial bulb size and advancement of ontogenic development. Other than bulblet production through bulb scale explant, this study represents the first report on the method of in vitro bulb production of lily through re-culture by in vitro pathway with a comparison of the timelines and ontogenic development obtained from in vitro versus conventional pathway.

Aflatoxins in feeds cause great health hazards to animals and in advance, to human. Potential of crude clays designated AC, KC, CC and MC and ashes VA and RA were evaluated for their capacity to adsorb aflatoxins B₁ (AFB₁), B₂ (AFB₂), G₁ (AFG₁) and G₂ (AFG₂) relative to a commercial binder Mycobinder^R (Evonik Industries AG) using in-vitro technique. On average, CC, VA, KC, MC, AC, RA and Mycobind^R adsorbed 39.9%, 51.3%, 61.5%, 62.0%, 72.6%, 84.7% and 98.1% of the total aflatoxins in buffered solution, respectively. The capacity of AC and RA was statistically (p<0.05) better in binding aflatoxins next to Mycobind^R. Capacity of the TBM and Mycobind^R to bind aflatoxins, seemed to follow the trend of their cation exchange capacity (CEC). The CEC (meq/100g) of CC, MC, KC, VA, AC, RA and Mycobind^R were 7.0, 15.4, 18.8, 25.4, 27.2, 27.2 and 38.9, respectively. On average 96.3%, 42.7%, 80.8% and 32.1% of AFB1, AFB2, AFG1 and AFG2 were adsorbed, respectively. Binding capacity of the clays and ashes relative to Mycobind^R was about 100% for AC and RA, 50% for KC, MC and VA and 33.3% for CC. The AC and RA seem to be promising resources in binding aflatoxins in solution.

Background: Zebrafish (Danio rerio) is a model organism emerged for the study of human cancer. Compared with the murine model, the zebrafish model has several properties ideal for personalized therapies. The transparency of the zebrafish embryos and the development of the pigment-deficient “casper” zebrafish line give the capacity to directly observe cancer formation and progression in the living animal. Automatic quantification of cellular proliferation in vivo is critical to the development of personalized medicine. Methods: A new methodology was defined to automatically quantify the cancer cellular evolution. ZFTool was developed to establish a base threshold that eliminates the embryo auto-fluorescence and automatically measures the area and intensity of GFP (green-fluorescent protein) marked cells and define a proliferation index. Results: Proliferation index automatically computed on different targets demonstrates the efficiency of ZFTool to provide a good automatic quantification of cancer cell evolution and dissemination. Conclusion: Our results demonstrate that ZFTool is a reliable tool for the automatic quantification of the proliferation index, being a measure of cancer mass evolution in zebrafish eliminating the influence of its autofluorescence.

Breast cancer treatment mostly revolved around radiation therapy and surgical interventions, these treatments doesn’t provide satisfactory relief to the patients and carry unmanageable side-effects. Nanomaterials show promising results in treating cancer cells and have many advantages such as high biocompatibility, bioavailability and effective therapeutic capabilities. Interestingly, fluorescent magnetic nanoparticles have been used in many biological and diagnostic applications, but there is no report of use of fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) in the treatment of human breast cancer cells. In the present study, we have tested the effect FMSP-nanoparticles on human breast cancer cells (MCF-7). We have tested different concentrations (1.25µg/1mL, 12.5µg/mL and 50µg/1mL) of FMSP-nanoparticles in MCF-7 cells and evaluated the nanoparticles response morphometrically. Our results revealed that FMSP-nanoparticles produced a concentration dependent effect on the cancer cells, dose of 1.25µg/mL produced no significant effect on the cancer cell morphology and cell death, whereas dosages of 12.5µg/mL and 50µg/mL respectively showed significant nuclear augmentation, disintegration, chromatic condensation followed by dose dependent cell death. Our results demonstrate FMSP-nanoparticles have ability to induce cell death in MCF-7 cells and may be considered as a potential anti-cancer agent for breast cancer treatments.

Magnesium (Mg)-based biomaterials are promising candidates for bone and tissue regeneration. Alloying and surface modifications provide effective strategies for optimizing and tailoring their degradation kinetics. Nethertheless, biocompatibility analyses of Mg-based materials are challenging due to its special degradation mechanism with continous hydrogen release. In this context, the hydrogen release and the related (micro-) milieu conditions pretend to strictly follow in vitro standards based on ISO 10993-5/-12. Thus, special adaptions for the testing of Mg materials are necessary, which have been described in a previous study from our group. Based on these adaptions, further developments of a test procedure allowing rapid and effective in vitro cytocompatibility analyses of Mg-based materials based on ISO 10993-5/-12 are necessary. The following study introduces a new two-step test scheme for rapid and effective testing of Mg. Specimens with different surface characteristcis were produced by means of plasma electrolytic oxidation (PEO) using silicate-based and phosphate-based electrolytes. The test samples were evaluated for corrosion behavior, cytocompatibility and their mechanical and ostogenic properties. Thereby, two PEO ceramics could be identified for further in vivo evaluations.

Inhalation is the main route of exposure to airborne pollutants. To evaluate the safety and assess the risks of occupational hazards different testing approaches are used. 3D airway epithelial tissues allow to mimic exposure conditions in vitro, generates human-relevant toxicology data, allows to elucidate mode of action of pollutants. Gilian 3500 pumps equipped with Standard Midget Impingers were used to collect the airborne particulate from woodworking and metalworking environments. EpiAirway™ tissues were used to model half working day (4 h), full working day (8 h), and 3 working day exposures to occupational pollutants. Tissue viability was assessed using MTT assay. RT-qPCR analyses performed to analyze the expression of gelsolin, caspase-3, and IL-6. Tissue morphology was assessed by hematoxylin/eosin staining. Acute exposure to workspace pollutants slightly affected tissue viability and did not change the morphology. Both types of particles suppressed expression of gelsolin, with metalworking samples showing the most pronounced effect. A slight reduction in caspase-3 expression was observed. Particles from metalworking suppressed IL-6 expression. 3D Epithelial tissues can be used to model exposures to airborne pollutants. Exposure to particles from woodworking and metalworking had a minor effect on tissue viability but affected the expression of inflammation and apoptosis-related genes.

Antimicrobial resistance is on the rise, and there aren't enough new treatments to combat it. This might send the modern world back to the pre-antibiotic age. The molecular hybrids of pyrazolo[3,4-b]pyridine and triazole have been designed, synthesized, and analyzed for their drug-like molecule nature and in vitro analyses for their inhibition potentials against S. Aureus and K. Pneumoniae. The compounds CY-R2-25 and CY-R2-28 have been identified as the high potential molecules in this series based on in vitro experiments. CY-R2-25 has zone of inhibition values of 15 0.82 and 14 0.7, whilst CY-R2-28 has the zone of inhibition values of 18 0.95 and 16 0.82 against S. Aureus and K. Pneumoniae, respectively. MIC and MIB values for CY-R2-25 and CY-R2-28 against S. Aureus and K. Pneumoniae are 0.25 and 0.5, respectively.

The efficiency of producing embryos using in vitro technologies in livestock species rarely exceeds the 30 to 40% threshold, indicating that the proportion of oocytes that fail to develop after in vitro fertilization and culture is considerably large. Considering that the intrinsic quality of the oocyte is one of the main factors affecting blastocyst yield, the precise identification of non-invasive cellular or molecular markers that predict oocyte competence is of major interest to research and practical applications. The aim of this review was to explore the current literature on different non-invasive markers associated with oocyte quality in the bovine model. Apart from some controversial findings, the presence of cycle-related structures in ovaries, a follicle size between 6 and 10 mm, large number of surrounding cumulus cells, slightly expanded investment without dark areas, large oocyte diameter (>120 microns), dark cytoplasm, and the presence of a round and smooth first polar body have been associated to better competence. In addition, the combination of oocyte and zygote selection by BCB test and spindle imaging have the potential to further optimize the identification of oocytes with better developmental competence for in vitro-derived technologies in livestock species.

Dalbergia sissoo (shisham), an important timber yielding multipurpose tree species of the Indian subcontinent, has been afflicted with large scale mortality due to wilt in natural forests and plantations, causing huge economic losses. Fusarium solani f. sp. dalbergiae (Fsd) has been identified as one of the causal organisms for wilt disease in D. sissoo. Present study comprises in vitro screening of ten selected genotypes of D. sissoo against two strains of Fsd in a dual culture set up under axenic condition. Callus and plantlets of ten genotypes of host plant were multiplied in vitro and were inoculated with conidial suspension of two strains of Fsd at three concentrations; 1× 10¹, 1× 10³, and 1× 10⁵ conidia/ml. Gnotobiotic evaluation of dual culture set up shows variations among D. sissoo genotypes in their response towards in vitro Fsd infection; and two genotypes (14 and 66) exhibited resistance against the pathogen strains. Callus of genotypes 14 and 66 significantly restricted the fungal mycelium growth whereas callus of remaining eight genotypes were completely infested by Fsd mycelium within 9 days. Similarly, plantlets of genotype 14 and 66, had lesser disease severity and remained green, and had fewer necrotic lesions in the roots whereas plantlets of remaining eight genotypes died within 15 days.

Microfluidics is facing critical challenges in the quest of miniaturizing, integrating, and automating in vitro diagnostics, including the increasing complexity of assays, the gap between the macroscale world and the microscale devices, and the diverse throughput demands in various clinical settings. Here a “3D extensible” microfluidic design paradigm that consists of a set of basic structures and unit operations was developed for constructing any application-specific assay. Four basic structures- check valve (in), check valve (out), double-check valve (in and out), and on-off valve, were designed to mimic basic acts in biochemical assays. By combining these structures linearly, a series of unit operations can be readily formed. We then proposed a “3D extensible” architecture to fulfill the needs of the function integration, the adaptive “world-to-chip” interface, and the adjustable throughput in the X, Y, and Z directions, respectively. To verify this design paradigm, we developed a fully integrated loop-mediated isothermal amplification microsystem that can directly accept swab samples and detect Chlamydia trachomatis automatically with a sensitivity one order higher than that of the conventional kit. This demonstration validated the feasibility of using this paradigm to develop integrated and automated microsystems in a less risky and more consistent manner.

The aim of this study was to gather preliminary data about the potential inhibitory effects and contributions of live foods used from 3 to 32 days after hatching (DAH) in routine feeding protocols on protease activities of meagre, Argyrosomus regius (Asso 1801) larvae, using in vitro techniques. Enriched rotifer, Artemia nauplii and Artemia metanauplii were tested in the present study. The highest values of protease activities of meagre larvae at 7 DAH in 2013 and 2014 years were established. The lowest values at 15 DAH in 2013 and at 20 DAH in 2014 were observed. Protease activities of enriched rotifer, Artemia nauplii, and Artemia metanauplii were 21.76±0.31, 36.00±1.48–29.33±0.93, and 416.44±19.7–403.53±11.85 U/mg protein, respectively (p< 0.05). The highest inhibitions of live foods were observed at 7 DAH. The positive contributions of live food Artemia metanauplii’s on protease activities of meagre larvae were significant (p< 0.05). The inhibitory effects and positive contributions of live foods on survival and growth rates of meagre larvae, should be taken into account in meagre and other marine fish larvae’s future studies. Cysteine protease activities of Artemia sp. should be investigated to provide the higher growth and survival ratio from the feeding protocols used in marine fish larvae.

All cancer registries constantly show striking differences in cancer incidence by age and among tissues. For example, lung cancer is diagnosed hundreds of times more often at age 70 than at age 20, and this cancer in nonsmokers occurs thousands of times more frequently than heart cancer in smokers. An analysis of these differences using basic concepts in cell biology indicates that cancer is the end-result of the accumulation of cell divisions in stem cells. In other words, the main determinant of carcinogenesis is the number of cell divisions that the DNA of a stem cell has accumulated in any type of cell from the zygote. Cell division, process by which a cell copies and separates its cellular components to finally split into two cells, is necessary to produce the large number of cells required for living. However, cell division can lead to a variety of cancer-promoting errors, such as mutations occurring during DNA replication, chromosome aberrations arising during mitosis, errors in the distribution of cell-fate determinants between the daughter cells, and failures to restore physical interactions with other tissue components. Some of these errors are spontaneous, others are promoted by endogenous DNA damage occurring during quiescence, and others are influenced by pathological and environmental factors. The cell divisions required for carcinogenesis are primarily caused by multiple local and systemic physiological signals rather than by errors in the DNA of the cells. As carcinogenesis progresses, the accumulation of DNA errors promotes cell division and eventually triggers cell division under permissive extracellular environments. The accumulation of cell divisions in stem cells drives not only the accumulation of the DNA alterations required for carcinogenesis, but also the formation and growth of the abnormal cell populations that characterize the disease. This model of carcinogenesis provides a new framework for understanding the disease and has important implications for cancer prevention and therapy.

High-grade gliomas are the most common and aggressive adult primary brain tumors with a median survival of only 12-15 months. Current standard therapy consists of maximal safe surgical resection followed by DNA-damaging agents, such as irradiation and chemotherapy that can delay but not prevent inevitable recurrence. Some have interpreted glioma recurrence as evidence of glioma stem cells which persist in a relatively quiescent state after irradiation and chemotherapy, before the ultimate cell cycle re-entry and glioma recurrence. Conversely, latent cancer cells with a therapy-induced senescent phenotype have been shown to escape senescence, giving rise to more aggressive stem-like tumor cells than those present in the original tumor. Therefore, approaches are needed to either eliminate or keep these glioma-initiating cells in a senescent state for a longer time to prolong survival. In our current study, we demonstrate that the radiation-induced cell cycle inhibitor P21 can provide a powerful route to induce cell death in short-term explants of PDXs derived from three molecularly diverse human gliomas. Additionally, cells not killed by P21 overexpression were maintained in a stable senescent state for longer than control cells. Collectively, these data suggest that P21 activation may provide an attractive therapeutic target to improve therapeutic outcomes.

In this study, lithium reaction distributions, dependent on charge-discharge rate, were nondestructively visualized for a commercial lithium-ion battery, using the Compton scattering imaging technique. By comparing lithium reaction distributions obtained from two different charge-discharge speeds, residual lithium ions were detected at the center of the negative electrode on a fully discharged state, by relatively high-speed discharge rate. Moreover, we confirmed that inhomogeneous reactions were facilitated on a relatively high-speed charge-discharge rate, in both the negative and positive electrodes. A feature of our technique is that it can be applied to commercially used lithium-ion batteries, because it uses high-energy X-rays with a high penetration power. Our technique thus opens a novel analyzing pathway for developing advanced batteries.

With the increase in life expectancy and consequent aging of the world’s population, the prevalence of many neurodegenerative diseases is increasing, without concomitant improvement in diagnostics and therapeutics. These diseases share neuropathological hallmarks, including mitochondrial dysfunction. In fact, as mitochondrial alterations appear prior to neuronal cell death at an early phase of the disease onset, the study and modulation of mitochondrial alterations rise as promising strategies to predict and prevent neurotoxicity and neuronal cell death before the onset of cell viability alterations. In this work, differentiated SH-SY5Y cells were treated with the mitochondrial-targeted neurotoxicants 6-hydroxydopamine and rotenone. These compounds were used at different concentrations and for different time points to understand the similarities and differences in their mechanisms of action. To accomplishing this, data on mitochondrial parameters was acquired and analyzed using unsupervised (hierarchical clustering) and supervised (decision tree) machine learning methods. Both biochemical and computational analyses resulted in an evident distinction between the neurotoxic effects of 6-hydroxydopamine and rotenone, specifically for the highest concentrations of both compounds.

Thai basil is a renowned medicinal plant and a rich source of bioactive antioxidant compounds having several health benefits, with actions to prevent of cancer, diabetes and cardiovascular disease. Plant cell and tissue culture technologies can be routinely established as an important, sustainable and low-cost biomass source for the production of high-value phytochemicals. The current study aimed at developing an effective protocol for the production of Thai basil leaf derived callus cultures with sustainable and high production of biomass and antioxidants as an alternative of leaves production. MS basal medium with various concentrations of plant growth regulators (PGRs) compatible with nutraceutical applications (i.e., gibberellic acid (GA3) and 6-benzylaminopurine (BAP) either alone or in combination with naphthalene acetic acid (NAA)) were evaluated. Among all tested PGRs, the combination BAP:NAA (5 mg/L:1 mg/L) yield maximum biomass accumulation (fresh weight (FW): 190 g/L and dry weight (DW): 13.05 g/L) as well as enhanced phenolic (346.08 mg/L) production. HPLC quantification analysis indicated high productions of chicoric acid (35.77 mg/g DW) and rosmarinic acid (7.35 mg/g DW) under optimized callus culture conditions. Antioxidant potential was assessed using both in vitro cell free and in vivo cellular antioxidant assays. Maximum in vitro antioxidant activity DPPH (93.2 % of radical scavenging activity) and ABTS (1322 µM Trolox equivalent antioxidant capacity) was also observed for the extracts from callus cultures grown on optimal conditions. In vivo cellular antioxidant activity assay confirmed the effective protection against oxidative stress of the corresponding extract by the maximum inhibition of ROS and RNS production. Compared to commercial leaves, callus extracts showed higher production of chicoric acid and rosmarinic acid associated with higher antioxidant capacity. In addition, this biological system also has a large capacity for continuous biomass production, thus demonstrating its high potential for possible nutraceutical applications.

PcALCL mainly concerns elderly patients. It is a large CD30+ T-cell neoplasm composed of large cells with anaplastic, pleomorphic or immunoblastic morphology, with exclusively cutaneous onset and localization. The clinical course of pcALCL is predominantly indolent. Most elderly patients with lymphoma tend to have a sedentary lifestyle, which has a negative effect on their quality of life (QoL) and on their survival. Several studies indicate that exercise has a positive impact on QoL because it reduces peak oxygen consumption, improves physical capacity, increases self-esteem, reduces accumulated stress and promotes relaxation. Therefore, particularly in indolent lymphomas, it is necessary to indicate a program of physical activity to be practiced systematically. The complete surgical excision and local radiotherapy are the first line gold standard in pcALCL with solitary lesion.

Circulating tumor cells (CTCs) in the peripheral blood are the precursors to distant metastasis but the underlying mechanisms are poorly understood. This study aims at understanding the molecular features within CTCs in relation to their metastatic potential. Using in vitro CTC models, in which breast cancer cell lines are cultured in non-adherent conditions simulating the microenvironment in the blood stream, we found that suspension culture resulted in resistance to TNF-related apoptosis inducing ligand (TRAIL)-mediated cell death. Such a resistance was directly correlated with a reduction in surface and total levels of DR5 protein. In the non-adherent state, cells underwent rapid autophagic flux characterized by an accumulation of autophagosome organelles. Notably, DR5 was translocated to autophagosomes and underwent lysosomal degradation. Our data suggest that CTCs may evade TNF cytokine mediated immune surveillance through downregulation of DR expression. The data warrants further studies in cancer patients to find the status of DRs and other molecular features within primary CTCs in relation to disease progression or chemoresistance.

Conventional chemotherapy for colorectal cancer (CRC) gives only a small increase in patient survival, since it is often diagnosed in late stages, when tumor has disseminated to other organs. Besides, it is common to observe that malignant cells acquire tumor escape mechanisms which leads to therapy resistance. Considering these facts, the discovery of new molecules with therapeutic potential has become an invaluable tool in chemoprevention. In this context, we previously evaluated two hybrids (SAC-CAFA-MET and SAC-CAFA-PENT) which exhibited selective cytotoxicity against SW480, with better results than the conventional chemotherapeutic agent (5-fluorouracil; 5-FU). Here, we investigated a little deeper in the possible mechanism of these molecules to identify potential therapeutic alternatives for the treatment of CRC. Both compounds induced cell damage and reduced ROS formation. Further evaluations showed that SAC-CAFA-MET induces cell death independent from caspases and p53, but probably mediated by the negative regulation of the proapoptotic Bcl-2. In addition, the lack of activation of caspase 8 and the positive regulation of caspase 3 induced by SAC-CAFA-PENT suggest this compound acts through an apoptotic mechanism, probably initiated by intrinsic pathway. Besides, the down regulation of IL-6 by SAC-CAFA-PENT suggests it also induces a significant anti-inflammatory process. In addition, docking studies would suggest caspase-3 modulation as the primary mechanism by which hybrids elicits apoptosis in human colorectal adenocarcinoma SW480. Meanwhile, DFT calculations suggest that hybrids would produce effects in modulation of ROS in SW480 cells via hydrogen atom transfer pathway (HAT). Finally, both, SAC-CAFA-MET and SAC-CAFA-PENT displayed a favorable pharmacokinetic profile. The current work highlights the potential of the lead compounds SAC-CAFA-MET and SAC-CAFA-PENT as potential agents for colorectal cancer chemoprevention.

Abstract Antibacterial activities can be improved using mixed ligands. Mixed ligands involved in this research are sodium sulfadiazine (Na-sfz) and dithiocarbamate (ai-dtc). One-pot synthesis was used to synthesize ligand of aniline dithiocarbamate (ai-dtc) and the corresponding coordination compounds of [VO(sfz)(ai-dtc)] and [Zn(sfz)(ai-dtc)]. Crystals of ai-dtc, which grew from the solution when refrigerated after five days, were diffracted with technique of single crystal x-ray crystallography to reveal the structure. Other characterization techniques involving physicochemical parameters, FT-IR, UV-Vis and NMR (1H NMR and 13C NMR) were carried out on ligands of ai-dtc, sfz and corresponding coordination compounds. Differences in results of FT-IR, UV-Vis and NMR between ligands and their respective metal ions confirmed the coordination. The in vitro antibacterial studies showed that the ligands (not the metal complexes) had modest activity against Gram negative bacteria: Staphylococcus aureus, whereas, the coordination compounds had modest activities against the Gram negative bacteria: Escherichia coli and Pseudomonas aeruginosa.

There is a huge interest in developing novel hollow fiber (HF) membranes able to modulate neural differentiation to produce in vitro blood-brain barrier (BBB) models for biomedical and pharmaceutical research, due to the low cell-inductive properties of the polymer HFs used in current BBB models. In this work, poly(ε-caprolactone) (PCL) and composite PCL/graphene (PCL/G) HF membranes were prepared by phase inversion and were characterized in terms of mechanical, electrical, morphological, chemical, and mass transport properties. The presence of graphene in PCL/G membranes enlarged the pore size and the water flux and presented significantly higher electrical conductivity than PCL HFs. Biocompatibility assay showed that PCL/G HFs significantly increased C6 cells adhesion and differentiation towards astrocytes, may be attributed to their higher electrical conductivity in comparison to PCL HFs. On the other hand, PCL/G membranes produced a cytotoxic effect on the endothelial cell line HUVEC presumably related with a higher production of intracellular reactive oxygen species induced by the nanomaterial in this particular cell line. These results prove the potential of PCL HF membranes to grow endothelial cells and PCL/G HF membranes to differentiate astrocytes, the two characteristic cell types that could develop in vitro BBB models in future 3D co-culture systems.

Wolbachia are intracellular endosymbionts of several invertebrate taxa, including insects and nematodes. Although Wolbachia DNA has been detected in ticks, its presence is generally associated with parasitism by insects. To determine whether or not Wolbachia can infect and grow in tick cells, cell lines from three tick species, Ixodes scapularis, Ixodes ricinus and Rhipicephalus microplus, were inoculated with Wolbachia strains wStri and wAlbB isolated from mosquito cell lines. Homogenates prepared from fleas collected from cats in Malaysia were inoculated into an I. scapularis cell line. Bacterial growth and identity were monitored by microscopy and PCR amplification and sequencing of fragments of Wolbachia genes. The wStri strain infected Ixodes spp. cells and was maintained through 29 passages. The wAlbB strain successfully infected Ixodes spp. and R. microplus cells and was maintained through 2-5 passages. A novel strain of Wolbachia belonging to the supergroup F, designated wCfeF, was isolated in I. scapularis cells from a pool of Ctenocephalides sp. cat fleas and maintained in vitro through two passages over nine months. This is the first confirmed isolation of a Wolbachia strain from a flea and the first isolation of any Wolbachia strain outside the “pandemic” A and B supergroups. The study demonstrates that tick cells can host multiple Wolbachia strains, and can be added to panels of insect cell lines to improve success rates in isolation of field strains of Wolbachia.

Engineering of drug nanocarriers combining fine-tuned mucoadhesive/mucopenetrating properties is currently being investigated to ensure more efficient mucosal drug delivery. Aiming to improve the transmucosal delivery of hydrophobic drugs, we designed a novel kind nanogel produced by the self-assembly of amphiphilic chitosan graft copolymers ionotropically crosslinked with sodium tripolyphosphate. In this work, we synthesized for the first time chitosan-g-poly(methyl methacrylate) nanoparticles thiolated by the conjugation of N-acetyl cysteine. First, we confirmed that both non-crosslinked and crosslinked nanoparticles in the 0.05-0.1% w/v concentration range display very good cell compatibility in two cell lines that are relevant to oral delivery, Caco2 cells that mimic the intestinal epithelium and HT29-MTX cells that produce mucin. Then, we evaluated the effect of crosslinking, nanoparticle concentration and thiolation on the permeability in vitro utilizing monolayers of (i) Caco2 and (ii) Caco2:HT29-MTX cells (9:1 cell number ratio). Results confirmed that the ability of the nanoparticles to cross Caco2 monolayer was affected by the crosslinking. In addition, thiolated nanoparticles interact more strongly with mucin, resulting in a decrease of the apparent permeability coefficient (Papp) compared to the pristine nanoparticles. Moreover, for all the nanoparticles, higher concentration resulted in lower Papp suggesting indicating that the transport pathways could undergo saturation.

Therapeutically effective treatments of cancer are limited. To calibrate the efficiency of the novel technique we recently discovered to modulate cancer cell viability using tuned electromagnetic fields; H1299 human lung cancer cells were irradiated in a sweeping regime of W-band (75-105 GHz) millimeter waves (MMW) at 0.2 mW/cm² (2 W/m²). Effects on cell morphology, cell death and senescence were examined and compared to that of non-tumorigenic MCF-10A human epithelial cells. MMW irradiation led to alterations of cell and nucleus morphology of H1299 cells, significantly increasing mortality and senescence over 14 days of observation. Extended irradiation of 10 minutes duration resulted in complete death of exposed H1299 cell population within two days, while healthy MCF-10A cells remained unaffected even after 16 minutes of irradiation under the same conditions. Irradiation effects were observed to be specific to MMW treated H1299 cells and absent in the control group of non-irradiated cells. MMW irradiation affected nuclear morphology of H1299 cells only and not of the immortalized MCF-10A cells. Irradiation with low intensity MMW shows an antitumor effect on H1299 lung cancer cells. This method provides a novel treatment modality enabling targeted specificity for various types of cancers.

There is a strong anticipated future for human pluripotent stem cell-derived hepatocytes (hiPS-HEP), but so far their use has been limited due to insufficient functionality. We investigated the potential of hiPS-HEP as an in vitro model for metabolic diseases by combining transcriptomics with multiple functional assays. The transcriptomics analysis revealed that 86% of the genes were expressed at similar levels in hiPS-HEP as in human primary hepatocytes (hphep). Adult characteristics of the hiPS-HEP were confirmed by the presence of important hepatocyte features, e.g. Albumin secretion and expression of major drug metabolizing genes. Normal energy metabolism is crucial for modeling metabolic diseases, and both transcriptomics data and functional assays showed that hiPS-HEP were similar to hphep regarding uptake of glucose, LDL and fatty acids. Importantly, the inflammatory state of the hiPS-HEP was low under standard conditions, but in response to lipid accumulation and ER stress the inflammation marker TNFα was upregulated. Furthermore, hiPS-HEP could be co-cultured with primary hepatic stellate cells both in 2D and in 3D spheroids, paving the way for using these co-cultures for modeling NASH. Taken together, hiPS-HEP have the potential to serve as an in vitro model for metabolic diseases. Furthermore, differently expressed genes identified in this study can serve as targets for future improvements of the hiPS-HEP.

Background: The t (2; 5) chromosomal rearrangement and resulting nucleophosmin (NPM1) -ALK fusion was first observed in 1994 in anaplastic large cell lymphoma (ALCL), a T-cell lymphoma responsive to cyclophosphamide, abriblastine, vincristine and prednisone in approximately 80% of cases; refractory cases usually respond favorably to brentuximab-vedotin. These treatments are regarded as a bridge to allogeneic hematopoietic stem cell transplantation (allo-SCT). Nowadays, transplant procedures and monitoring of chemotherapy patients proceed very slowly because the SARS-CoV-2 pandemic has heavily clogged the hospitals in all countries. Results: A 40-year-old Caucasian woman was first seen at our clinical center in June 2020. She had ALCL ALK +, a history of failure to two previous therapeutic lines and was in complete remission after 12 courses of Brentuximab, still pending allo-SCT after two failed donor selection. Facing of a new therapeutic failure, we requested the Italian drug regulatory agency, and obtained the authorization, to administer 250 mg twice a day of Crizotinib, a drug incomprehensibly not registered for ALCL ALK +. Conclusions: The response to Crizotinib was optimal, since no adverse event occurred, and CT-PET persisted negative; this drug has proved to be a valid bridge to allo-SCT

Engineered nanomaterials (ENMs) are of significant relevance due to their unique properties, which have been exploited for widespread applications. Cerium oxide nanoparticles (CeO2-NPs) are one of most exploited ENM in the industry due to their excellent catalytic and multi-enzyme mimetic properties. Thus, toxicological effects of these ENMs should be further studied. Acute and subchronic toxicity of CeO2-NPs were assessed. First an in vitro multi-dose short-term (24h) toxicological assessment was performed in three different cell lines: A549 and Calu3, representing the lung tissue, and 3T3 as an interstitial tissue model. After that, a sub-chronic toxicity assessment (90 days) of these NPs was carried out on a realistic and well stablished reconstituted primary human airway epithelial model (MucilAir™), cultured at the Air-Liquid Interface (ALI), to study long-term effects of these particles. Results showed minor toxicity of CeO2-NPs in acute exposures. However, in subchronic exposures, cytotoxic and inflammatory responses were observed in the human airway epithelial model after 60 days of exposure to CeO2-NPs. These results suggest that acute toxicity approaches may underestimate the toxicological effect of some ENM, highlighting the need of subchronic toxicological studies in order to accurately assess the toxicity of ENM and their cumulative effects in the organism.

Biomarker directed selection of targeted anti-neoplastic agents such as immune check-point inhibitors, small molecule inhibitors and monoclonal antibodies form an important aspect of cancer treatment. Immunohistochemistry (IHC) analysis of the tumor tissue is the method of choice to evaluate the presence of these biomarkers. However, a significant barrier to biomarker testing on tissue is the availability of an adequate amount of tissue and need for repetitive sampling due to tumor evolution. Also, tumor tissue testing is not immune to inter- and intra-tumor heterogeneity. We describe the analytical and clinical validation of a Circulating Tumor Cell (CTC) assay to accurately assess the presence of PD-L1 22C3 and PD-L1 28.8, ER, PR and HER2, from patients with solid tumors to guide the choice of suitable targeted therapies. Analytically, the test has high sensitivity, specificity, linearity and precision. Based on a blinded case control study, the clinical sensitivity and specificity for PD-L1 (22C3 and 28.8) was determined to be 90% and 100% respectively. The clinical sensitivity and specificity was 83% and 89% for ER; 80% and 94% for PR; 63% and 89% for HER2 (by ICC); and 100% and 92% for HER2 (by FISH), respectively. The performance characteristics of the test support its suitability and adaptability for routine clinical use.

Whether the different NR-AMPs could ever be utilized as drugs not only against prokaryotic (bacteria) pathogens but eukaryotic (fungal pathogens, and parasitic protists) depends on the side effects. To get experimental experience about the option of applying EPB-produced antimicrobials to pathogens, and parasites of veterinary significance, we present here the results of an in vitro, and an accompanying in vivo study on chicken. In the in vitro study, we tested the cytotoxic potential of the cell-free conditioned culture media (CFCM) of three entomopathogenic bacterium species, - X. budapestensis, DSM16342 (EMA); X. szentirmaii DSM16338 (EMC); Photorhabdus luminescens ssp. akhurstii TT01 - on chicken tissue culture cells, namely, on the Leghorn Male Hepatoma (LMH), [92] cells, (a permanent confluent hepato-carcinoma cell line). Each CFCM proved rather cytotoxic in this test. In the in vivo study, we fed freshly hatched male broiler chickens for 42 days with XENOFOOD [39] which contained autoclaved cultures of EMA, and EMC). These bacteria were grown on standard chicken (starter and grower) [HM3] [u4] feed, and the whole culture was used as a “food supplement”. [HM5]. It had been known that these EPB species cannot grow that is, not viable) atbody temperature (above 33 C).

Background: Cancer has been one of the most critical health problems during the past decades which require serious consideration, especially in developing countries. Methods: 80 parents of the children with different types of cancers were studied via both questionnaire and person-to-person interview after announcing their informed consent. Results: The highest delay in patients' initial referral was due to the following factors: lack of attention or ignoring the first symptoms, delay in referring to the physician, low economic status and even lack of family support for the patient. In addition, visiting several doctors after the initial diagnosis, uncertainty about the first proposed method, and high cost of treatment can be mentioned as the main causes of delays in the start of treatment. Conclusion: Education plays an important role in identifying the signs of cancer. In addition, proper relationship and cooperation between the health system and physicians as well as provision of adequate information to patients could lead to the long-term cooperation of these patients in continuing their treatment.

Current article presents the study of psychological wellbeing of adolescents (n=168, age 15-17) gifted in math, humanities and sports and educated in advanced programs for gifted children. Theoretical framework of this study is eudemonic concept of psychological wellbeing by C. Ryff. Psychological wellbeing is measured with Ryff wellbeing scales in Russian adaptation by L.V. Zhukovskaya and E.G. Troshikhina. The study is aimed at understanding differences in psychological wellbeing of gifted teenagers connected to gender and type of giftedness. The results suggest that general wellbeing score did not differ for adolescents with different types of giftedness or of different genders. Separate components of psychological wellbeing, such as purpose in life and self-acceptance, are influenced by activity connected to the talent. Gender differences are subjected to age-specific trends of personal development in adolescence. Type of giftedness might reinforce these trends.

With Internet of Things (IoT) gaining presence throughout different industries a lot of new technologies have been introduced to support this undertaking. Implications on one such technology, wireless systems allowed for the use of different communication methods to achieve the goal of transferring data reliably, with more cost efficiency and over longer distances. Anywhere from a single house with only a few IoT devices such as a smart light bulb or a smart thermostat connected to the network, all the way to a complex system that can control power grids throughout countries, IoT has been becoming a necessity in everyday lives. This paper presents an overview of the devices, systems and wireless technologies used in different IoT architectures (Healthcare, Vehicular Networks, Mining, Learning, Energy, Smart Cities, Behaviors and Decision Making), their upbringings and challenges to this date and some foreseen in the future.

In an effort to discover an effective and selective antitumour agent, synthesis and anti-cancer potential of 4-(pyridin-4-yl)-6-(thiophen-2-yl)pyrimidin-2(1H)-one (SK-25), which has been reported earlier by us with significant cytotoxicity towards MiaPaCa-2 malignant cells, with an IC₅₀ value of 1.95 μM and was found to instigate apoptosis. In the present study, the antitumour efficacy of SK-25 was investigated on Ehrlich ascites tumour (solid), Sarcoma 180 (solid) tumour and Ehrlich ascites carcinoma. The compound was found to inhibit tumour development by 94.71% in Ehrlich ascites carcinoma (EAC), 59.06% in Ehrlich tumour (ET, solid) and 45.68% in Sarcoma-180 (solid) at 30 mg/kg dose. Additionally, SK-25 was established to be non-toxic at a maximum tolerated dose of 1000 mg/kg in acute oral toxicity in Swiss-albino mice. Computer-based predictions also show that the compounds could have an interesting DMPK profile. The current study provides insight for further investigation of the antitumour potential of the molecule.

In this paper, we discuss major issues of mathematics teaching and learning in Nepal. The issues coming from theories such as social and radical constructivism suggest that teachers are not trained to use such approach in teaching mathematics, and there is a lack of teaching aids and materials and technological tools. The issues related to social aspects are gender issues, language issues, social justice issues, and issues related to the achievement gap. The cultural issues are related to the diversity of language and ethnicity. The issues related to political aspects are equity and access, economic status, pedagogical choice, and professional organizations and unions. The issues related to technology include the technological skills, use of technology, and affordance. Finally, we suggest that all the stakeholders should pay attention to resolving these issues by improving the curriculum, training teachers, resourcing the classroom with locally made and new technological tools.

Physics behind collimated highly directional nature of lasers, and factors that keep the seven coloured waves that form white light together during their journey from Sun to Earth, in the face of the natural disruptive forces, is not fully understood. Energy levels were measured, in terms of alterations in induced current and voltage, in beams from a red laser, white LED light and the Sunlight before and during their disruption by diffusers (frosted glass for the lasers) and diffractors (diffraction grating for the white light) using a photovoltaic solar cell panel attached to a digital multimeter. Results show that disruption of the beams results in release of extra energy named as ‘Latent Light Binding’ Energy’. It is hypothesized that the ‘binding’ energy keeps laser waves firmly bound together both end-on and side-on enabling laser beams to travel long distances in collimated manner. Likewise, the 7 coloured waves that constitute white light are kept together, probably side-on, in their journey from the Sun to the Earth. The observation that diffraction of sunbeam is associated with increased power generation provides a new lead to improve harnessing of solar energy, where, currently, the focus is mainly on improving efficiency of photovoltaic cell.

Oxalate, a compound produced by many edible plants and as a terminal metabolite in the liver of mammals, is a toxin that has a detrimental role to human health. Humans and other mam-mals do produce the enzymatic machinery to degrade oxalate. However, numerous oxa-late-degrading bacteria reside in the mammalian gut and thus provide an important function for hosts. The current review focuses on the environmental factors that influence the efficacy of pro-biotic oxalate-degrading bacteria, relative to oxalate metabolism. We describe the mechanism of oxalate catabolism and its consumption by obligate and facultative anaerobic oxalate-degrading bacteria, in both in vitro and in vivo environments. We also explore the environmental variables that impact oxalate degradation. Studies on single species degrade oxalate have not shown a strong impact on oxalate metabolism especially in high oxalate conditions such as consumption of foods high in oxalate (such as coffee and chocolate for humans or halogeton in animal feed). Considering effective variables which enhance oxalate degradation could be used in application of effective probiotic as a therapeutic tool in individuals with hyperoxaluria. This study indicates probiotics can be considered a good source of naturally occurring oxalate degrading agent in human colon

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

Introduction: The combination of Virtual Screening (VS) techniques with in vivo screening in the zebrafish model is currently being used in tandem for drug development in a faster and more efficient way. Areas covered: We review the different virtual screening techniques, the use of zebrafish as a vertebrate model for drug discovery and the synergy that exists between them. Expert opinion: We highlight the advantages of combining virtual and zebrafish larvae screening for drug discovery. On the one hand, VS is a faster and cheaper tool for searching active compounds and possible candidates for therapy than in vivo screening when processing large compound libraries. On the other hand, zebrafish larvae form a vertebrate model which allows in vivo screening of large amounts of the compounds. Importantly physiology and chemical response are mostly conserved between zebrafish and mammals. The availability of the transgenic and mutant zebrafish lines allows an analysis of a specific phenotype upon treatment along with toxicity, off-target effect, side effects, and dosage. Advantages of VS, in vivo whole animal approach screening, and the screening combinations are also reviewed.

The Environmental interactions contributed to the processes of settlement and development of the first settlers at southern Peru 15,000 BC. The determination of this process is based on paleoclimatic studies at southern Peru and ethnoarchaeological evidence. The determination of this process is based on paleoclimatic studies of southern Peru and ethnoarchaeological evidence; establishing as a result of this analysis the hypothesis of environmental interaction and territorial occupation of the first hunter-gatherer populations until their consolidation, dominating the geographical space from Tacna. The Disruptive disaster events and their effects on climate during the Peruvian Paleolithic resulted in the origin of local societies that shaped the Tiawanaku societies of the early horizon at Southern Peru and Northern Chile.

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

Academic entrepreneurship focuses on commercialization of research. Even though it is practiced worldwide for decades, Bangladesh is a newcomer in this segment. In Bangladesh only 2 Universities have Technology Transfer Offices or TTOs which are established with the sole focus of commercialization of researches of the students and the faculty members of the Universities. This article focuses on worldwide practices of technology transfer and academic entrepreneurial activities and also explores the opportunities and challenges of such entrepreneurs through detail investigation of the existing body of knowledge. Apart from exploring the problems and prospect of academic entrepreneurship in Bangladesh, this article also introduces the concept of Full-Service Knowledge Transfer Office (KTO), which existing literatures do not offer. The authors believe that by establishing such KTOs as a self-sustaining body, it is possible for an academic entrepreneur to stimulate, support and sustain their activities in Bangladesh. The concept of full service KTOs can also become models for other nations, specially the developing ones, to establish and nurture a culture of academic entrepreneurship.

Far-red fluorescent reporter genes can be used for tracking cells non-invasively in vivo using fluorescence imaging. Here, we investigate the effectiveness of the far-red fluorescent protein, E2-Crimson (E2C), for tracking mouse embryonic cells (mESCs) in vivo following subcutaneous administration into mice. Using a knock-in strategy, we introduced E2C into the Rosa26 locus of an E14-Bra-GFP mESC line, and after confirming that the E2C had no obvious effect on the phenotype of the mESCs, we injected them into mice and imaged them over 9 days. The results showed that fluorescence intensity was weak, and cells could only be detected when injected at high densities. Furthermore, intensity peaked on day 4 and then started to decrease, despite the fact that tumour volume continued to increase beyond day 4. Histopathological analysis showed that although E2C fluorescence could barely be detected in vivo at day 9, analysis of frozen sections indicated that all mESCs within the tumours continued to express E2C. We hypothesise that the decrease in fluorescence intensity in vivo was probably due to the fact that the mESC tumours became more vascular with time, thus leading to increased absorbance of E2C fluorescence by haemoglobin. We conclude that the E2C reporter has limited use for tracking cells in vivo, at least when introduced as a single copy into the Rosa26 locus.

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

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

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

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

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

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

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

Information and Communication Technology (ICT) education has attracted attention in recent years. But there are many issues specific to ICT education such as monetary cost, time, environment, teacher education system, motivation, curriculum, and health problems. In this paper, we investigated and considered the issues in ICT education in Japan from 10 viewpoints.

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

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

The human capital index is a multivariate variable used to measure the assessment of human resource productivity in the future. Human capital has a connection with economic development. Moreover, the study looks to analyses the relationship between Human Capital and Economic Growth indicators such as HCI and GDP. Human Capital relates to the development of individual skills to make them function more profitable for the national economy. The study was aimed at investigating the effect of population, the number of people engaged and the average annual hours worked by engaged persons on the human capital index. The analysis was in SPSS for the findings. Correlation tests were used for analysis. The study revealed that population, the number of people engaged and the average annual hours worked by engaged persons had a significant positive effect on the human capital index.

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

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

In the last decade, unprecedented progress in the development of neural networks influenced dozens of different industries, among which are signal processing for the electroencephalography process (EEG). Electroencephalography, even though it appeared in the first half of the 20th century, to this day didn’t change the physical principles of operation. But the signal processing technique due to the use of neural networks progressed significantly in this area. Evidence for this can serve that for the past 5 years more than 1000 publications on the topic of using machine learning have been published in popular libraries. Many different models of neural networks complicate the process of understanding the real situation in this area. In this manuscript, we provided the most comprehensive overview of research where were used neural networks for EEG signal processing.

Wireless Body Area Networks are composed of sensor nodes that may be implanted in the body or worn on it. A node is composed of a sensing unit, a processor and a radio unit. One of the nodes, the sink, acts as a gateway between the body area network and other networks such as the Internet. We propose a routing protocol that constructs paths between nodes such that the final network topology is a tree rooted at the sink. The protocol's aim is to increase network lifetime and reliability, and to adapt to network conditions dynamically. Moreover, the protocol enables communications between nodes and sink both in the upstream direction, from nodes to sink, and in the downstream direction from sink to nodes. When the network tree is constructed, a node chooses its parent, i.e., next hop to sink, by using one of various criteria. Namely, these are the number of hops between parent and sink, energy level of parent, received signal strength from parent, number of current parent's children, and a fuzzy logic function that combines multiple criteria. Moreover, as time progresses the tree structure may dynamically change to adapt to conditions such as the near-depletion of a routing node's energy. Simulation results show improvements in network lifetime and energy consumption over the older version of the protocol.

The out-of-time-ordered correlation (OTOC) function is an important new probe in quantum field theory which is treated as a significant measure of random quantum correlations. In this paper, with the slogan "Cosmology meets Condensed Matter Physics" we demonstrate a formalism using which for the first time we compute the Cosmological OTOC during the stochastic particle production during inflation and reheating following canonical quantization technique. In this computation, two dynamical time scales are involved, out of them at one time scale the cosmological perturbation variable and for the other the canonically conjugate momentum is defined, which is the strict requirement to define time scale separated quantum operators for OTOC and perfectly consistent with the general definition of OTOC. Most importantly, using the present formalism not only one can study the quantum correlation during stochastic inflation and reheating, but also study quantum correlation for any random events in Cosmology. Next, using the late time exponential decay of cosmological OTOC with respect to the dynamical time scale of our universe which is associated with the canonically conjugate momentum operator in this formalism we study the phenomena of quantum chaos by computing the expression for {\it Lyapunov spectrum}. Further, using the well known Maldacena Shenker Stanford (MSS) bound, on Lyapunov exponent, λ≤2π/β, we propose a lower bound on the equilibrium temperature, T=1/β, at the very late time scale of the universe. On the other hand, with respect to the other time scale with which the perturbation variable is associated, we find decreasing but not exponentially decaying behaviour, which quantifies the random correlation at out-of-equilibrium. Finally, we have studied the classical limit of the OTOC to check the consistency with the large time limiting behaviour.

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

Polymer flooding is one of the most successful chemical EOR methods, and is primarily implemented to accelerate oil production by sweep improvement. However, other benefits have extended the utility of polymers. During the last decade, it has been evaluated for an increasing number of fields, both offshore and onshore. This is a consequence of improved polymer properties, which extends the use to HTHS (high temperature high salinity) conditions and of improved understanding of flow mechanisms such as for heavy oil mobilization. A key issue in understanding polymer performance is to control and predict in-situ porous medium rheology. The first part of this paper reviews recent developments in understanding polymer flow in porous medium. Especially, polymer in-situ rheology and injectivity is discussed. The second part of this paper reports polymer flow experiments using the most applied polymer for EOR processes, HPAM (partially hydrolyzed polyacrylamide). The experiments address high rate near-wellbore behavior (radial flow) as well as reservoir rate steady state flow (linear flow) and discuss differences observed in terms of flow conditions. In addition, impact of oil on polymer rheology was investigated, and compared to single-phase polymer flow in Bentheimer sandstone rock material. Presence of oil leads to a reduction in apparent viscosity.

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

Chemical exposures from diverse sources merge on a limited number of molecular pathways described as toxicity pathways. Changes in the same set of molecular pathways in different cell and tissue types may generate seemingly unrelated health conditions. Today, no approaches are available to predict in an unbiased way sensitivities of different disease states and their combinations to multichemical exposures across the exposome. We propose an inductive in-silico workflow where sensitivities of genes to chemical exposures are identified based on the overlap of existing genomic datasets, and data on sensitivities of individual genes is further used to sequentially derive predictions on sensitivities of molecular pathways, disease states, and groups of disease states (syndromes). Our analysis predicts that conditions representing the most significant public health problems are among the most sensitive to cumulative chemical exposures. These conditions include six leading types of cancer in the world (prostatic, breast, stomach, lung, colorectal neoplasms, and hepatocellular carcinoma), obesity, type 2 diabetes, non-alcoholic fatty liver disease, autistic disorder, Alzheimer's disease, hypertension, heart failure, brain and myocardial ischemia, and myocardial infarction. Overall, our predictions suggest that environmental risk factors may be underestimated for the most significant public health problems.

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

Early development in mammals is characterized by the ability of each cell to produce a complete organism plus the extraembryonic, or placental, cells, defined as pluripotency. During subsequent development, pluripotency is lost, and cells begin to differentiate to a particular cell fate. This review summarizes the current knowledge of pluripotency features of bovine embryos cultured in vitro, focusing on the core of pluripotency genes (OCT4, NANOG, SOX2, and CDX2), and main chemical strategies for controlling pluripotent networks during early development. Finally, we will discuss the applicability of manipulating pluripotency during morula to blastocyst transition in cattle species.

The development of CRISPR associated proteins, such as Cas9, has led to increased accessibility and ease of use in genome editing. However, additional tools are needed to quantify and identify successful genome editing events in living animals. We developed a method to rapidly and quantitatively monitor gene editing activity non-invasively in living animals that also facilitates confocal microscopy and nucleotide level analyses at the end of study. Here we report a new CRISPR “footprinting” approach to activate luciferase and fluorescent proteins in mice as a function of gene editing. This system is based on experience with our prior Cre-detector system and is designed for Cas editors able to target LoxP including gRNAs including SaCas9 and ErCas12a [1, 2]. These CRISPRs cut specifically within LoxP, an approach that is a departure from previous gene editing in vivo activity detection techniques that targeted adjacent stop sequences. In this sensor paradigm, CRISPR activity was monitored non-invasively in living Cre reporter mice (FVB.129S6(B6)-Gt(ROSA)26Sortm1(Luc)Kael/J and Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo/J, which will be referred to as LSL and mT/mG throughout the paper) after intramuscular or intravenous hydrodynamic plasmid injections, demonstrating utility in two diverse organ systems. The same genome-editing event was examined at the cellular level in specific tissues by confocal microscopy to determine the identity and frequency of successfully genome-edited cells. Further, SaCas9 induced targeted editing at efficiencies that were comparable to Cre recombinase demonstrating high effective delivery and activity in a whole animal. This work establishes genome editing tools and models to track CRISPR editing in vivo non-invasively and to fingerprint the identity of targeted cells. This approach also enables similar utility for any of the thousands of previously generated LoxP animal models.

The environmental exposure of human in the daily and occupational activities to plasticizers may adversely affect human health, and thus represents a global issue. The altered expression of MicroRNAs (miRNAs) exerts an important pathogenic role linked also to the exposure to plasticizers. This systematic review summarizes the recent findings showing modified ex-pression of miRNAs in cancer due to plasticizers exposures. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, we performed a systematic review of the past ten years, focusing on the relationship between plasticizer exposures and expression of miRNAs cancer. Starting by 535 records, 17 articles were included. Results support the hypothesis that exposure to plasticizers cause changes or deregulation of a number of oncogenic miRNAs and showed that plasticizers interaction with several redundant miRNAs, such as let-7f, let-7g, miR-125b, miR-134, miR-146a, miR-22; miR-192, miR-222, miR-26a, miR-26b, miR-27b, miR-296, miR-324, miR-335, miR-122, miR-23b, miR-200, miR-29a and miR-21, might induce deep alterations. These genotoxic and oncogenic responses can eventually lead to abnormal cell signaling pathways and metabolisms that participate in many overlapped cellular processes, and miRNA level changes can be a useful tool for the toxicological assessment of environmental pollutants, including plastic additives and plasticizers

Scientists who hope to obtain a faculty position at a primarily undergraduate institution (PUI) need a distinct skill set and outlook on their future teaching and research career. To obtain a position at a PUI, candidates should 1) design a strategy for obtaining a faculty position that suits each individual’s career goals and aspirations, 2) prepare for the application process, on-campus interview, and contract negotiations, and 3) plan a strategy for the probationary period leading up to tenure and promotion. Given the different types of PUIs, candidates need to consider whether they seek a position that consists of all or mostly all teaching, or both teaching and research. Candidates should educate themselves on the expectations at PUI’s, including current thought, practice, and aspirations for science pedagogy, and gain teaching experience prior to seeking a suitable position. If the candidate’s goal is a position with both teaching and research, it is important to discuss with the current research mentor what projects the candidate can take with them to their new position. The candidate should also consider what types of projects will be successful with undergraduate student researchers in a PUI research environment Importantly, candidates should clearly demonstrate a commitment to diversity and inclusion in their teaching, research, and outreach, and application materials should demonstrate this. On interviews, candidates should be knowledgeable about the mission, values, and resources of the institution and how the candidate will contribute to that mission. Once hired, new faculty should discuss a formal or informal mentoring plan during the probationary period that includes peer evaluations on a regular basis, and maintain communication with the department chair or designated mentor regarding teaching, research, and service activities.

While obesity is recognized as a key global public health issue, there has been no research to date on the perceptions of care for people with this condition held by individuals in positions of organizational power. The aim of this study was therefore to describe the perceptions and experiences of clinical leaders and managers of providing care to inpatients with obesity at a metropolitan public health service. This study applied an interpretative phenomenological analysis (IPA) approach to qualitative research, conducting interviews with 17 participants. Their perceptions of care for inpatients with obesity encompassed both their personal understanding as an individual, and their observations about the organizational, patient and carer perspectives. Three overall themes were identified: 1) The problem of inpatients with obesity, 2) Inpatients with obesity as sources of risk and 3) Personal and professional perceptions of inpatients with obesity. While clinical leaders and managers were aware of potential impact of stigma and weight bias on the care given to this cohort, elements of implicit bias, stereotyping, ‘othering’ and ambivalence were frequently present in the data. Ongoing efforts to improve care for patients with obesity must therefore include efforts to address perceptions and attitudes at all organisational levels of the workforce.

The potential of A. baumannii for acquired resistance to last resort antibiotics (colistin and tigecycline) during treatment has important clinical implications, especially when dealing with patients failing to improve despite treatment with an active antimicrobial. However, the relevant literature remains scattered. Therefore, a systematic search was conducted in PubMed and Scopus. Several studies reported emergence of resistance to colistin or tigecycline during treatment, in most cases (86%) resulting in persistent or recurrent infections, especially in cases of emergent resistance without fitness cost. Lipopolysaccharide modification in the case of colistin and overexpression of efflux pumps in the case of tigecycline were the main mechanisms of resistance. Emergent colistin resistance is often associated with fitness cost resulting in re-emergence of the fitter and more virulent colistin susceptible strain after cessation of antibiotic pressure. Prospective studies are needed to determine the frequency of emergent resistance during treatment and its impact on patient outcomes.

The vastness of chemical-space constrains traditional drug-discovery methods to the organic laws that are guiding the chemistry involved in filtering through candidates. Leveraging computing with machine-learning to intelligently generate compounds that meet a wide range of objectives can bring significant gains in time and effort needed to filter through a broad range of candidates. This paper details how the use of Generative-Adversarial-Networks, novel machine learning techniques to format the training dataset and the use of quantum computing offer new ways to expedite drug-discovery.

We statistically investigate the Coronavirus Disease 19 (hereinafter Covid-19) epidemics, which is particularly invasive in Italy. We show that the high apparent mortality (or Case Fatality Ratio, CFR) observed in Italy, as compared with other countries, is likely biased by a strong underestimation of infected cases. To give a more realistic estimate of the mortality of Covid-19, we use the most recent estimates of the IFR (Infection Fatality Ratio) of epidemic, based on the minimum observed CFR, and furthermore analyse data obtained from the ship Diamond Princess, a good representation of a ‘laboratory’ case-study from an isolated system in which all the people have been tested. From such analyses we derive more realistic estimates of the real extension of the infection, as well as more accurate indicators of how fast the infection propagates. We then point out from the various explanations proposed, the dominant factors causing such an abnormal seriousness of the disease in Italy. Finally, we use the deceased data, the only ones estimated to be reliable enough, to predict the total number of infected people and the interval of time when the infection in Italy could stop.

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

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

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

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

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

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

The epidemic transmission of Zika virus (ZIKV) in Brazil has been identified as a cause of microcephaly and other neurological malformations in babies of ZIKV-infected women. This study provides a descriptive analysis, since the onset of symptoms to the delivery, of a cohort who were registered as having ZIKV infection in pregnancy, from November 2015 to December 2016. Suspected cases were registered at a referral center for infectious and tropical diseases in Manaus, in the Brazilian Amazonian region. A total of 834 women with suspected ZIKV in pregnancy were included, of whom 91.4% had confirmed pregnancy. Reverse-transcriptase polymerase chain reaction (RT-PCR) confirmed ZIKV infection in 42.2% of the cohort. In 35.2% of the cohort, ZIKV was the sole infection identified. Severe adverse pregnancy outcomes (abortion, stillbirth, or microcephaly) were observed in both RT-PCR ZIKV-positive (4.96%) and ZIKV-negative (2.15%) cases. Women with suspected ZIKV infection were much more likely to have adverse pregnancy outcomes if they were symptomatic during the first trimester of pregnancy (odds ratio 10.5; 95% confidence interval 4.0–27.0; p<0.001). Among pregnant women with suspected ZIKV infection, the occurrence of symptoms in the first trimester is associated with an especially high risk of severe adverse pregnancy outcomes.

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

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

Diabetes is a life-threatening disease and chronic diabetes affects the parts of the body including the liver, kidney and pancreas. The root cause of diabetes is mainly associated with oxidative stress produced by reactive oxygen species. The minocycline is a polyphenolic drug with excellent antioxidant activities. The objective of the present study was to investigate the antidiabetic potential of minocycline modified silver nanoparticles (Mino/AgNPs) against alloxan-induced diabetic mice. The Mino/AgNPs were synthesized using minocycline as reducing and stabilizing agents. UV-vis, FTIR, X-ray diffraction (XRD) and transmission electron microscopy (TEM) were applied for the characterization of Mino/AgNPs. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay was conducted to determine the antioxidant potential of newly synthesized Mino/AgNPs. The results revealed that the Mino/AgNPs showed higher radical scavenging activity (IC50 = 19.7 µg/mL) as compared to the minocycline (IC50 = 26.0 µg/mL) and ascorbic acid (IC50 = 25.2 µg/mL). Further, the Mino/AgNPs were successfully employed to examine their antidiabetic potential against Alloxan-induced diabetic mice. Hematological results showed that the mice treated with Mino/AgNPs demonstrated a significant decrease in fasting blood glucose level and lipid profile as compared to the diabetic group. The histopathological examination confirmed that the diabetic mice treated with Mino/AgNPs showed significant recovery and revival of histo-morphology of kidney, central vein of liver and islet cells of the pancreas compared to the diabetic mice. Hence Mino/AgNPs have good antidiabetic potential and could be an appropriate nanomedicine to prevent the development of diabetes.

In this paper, we use three different experimental methods (particle method, grid method and hybrid method) to model and simulate the smoke from the perspective of fluid dynamics. Through the comparison of different methods, we conclude: The particle method can avoid the numerical dissipation problem caused by grid calculation, but it also brings problems such as the distortion of the trajectory of the example. The grid method is accurate in calculation, but it is prone to numerical dissipation and loss of details. Finally, we choose the hybrid method to store the vorticity in the form of particles in vortex particles, avoiding the numerical dissipation problem caused by the use of grids, and including rich turbulence, which perfectly shows the simulation effect of smoke.

In the concept of the process signature, the relationship between a material load and the modification remaining in the workpiece is used to better understand and optimize manufacturing processes. The basic prerequisite for this is to be able to measure the loads occurring during the machining process in the form of mechanical deformations. Speckle photography is suitable for this in-process measurement task and is already used in a variety of ways for in-plane deformation measurements. The shortcoming of this fast and robust measurement technique based on image correlation techniques is that out-of-plane deformations in the direction of the measurement system cannot be detected and increases the measurement error of in-plane deformations. In this paper, we investigate a method that infers local out-of-plane motions of the workpiece surface from the decorrelation of speckle patterns and is thus able to reconstruct three-dimensional deformation fields. The implementation of the evaluation method enables a fast reconstruction of 3D deformation fields, so that the in-process capability remains given. First measurements in a deep rolling process show that dynamic deformations underneath the die can be captured and demonstrate the suitability of the speckle method for manufacturing process analysis.

Plants constituents are a reliable source of the remedial need of humanity for ages by being the basis of the traditional medicinal system and often serving as the prototype for designing modern medicine. Several plants are used in traditional medicine for ages without proper administration guidelines in terms of dosages. Several toxicological analyses revealed side-effects of such therapies beyond a specific dose. One such plant is Alstonia scholaris, widely used in numerous traditional medicines to treat diseases like ulcers, asthma, diabetes, etc. The present study investigated the neurotoxic effect of the plant extract through oxidative stress in Swiss albino mice. The treated mice showed anxiety, neophobic and depression-like properties compared to control mice. The biochemical parameters show an increase in Malondialdehyde (MDA) concentration while decreasing the total protein content in different brain regions of treated mice. The Glutathione Reductase (GR) activity shows an increase in treated mice compared to the control one. The study indicates that Alstonia scholaris may cause severe damage to the central nervous system when administered without a proper guideline.