The role of insurance in financial inclusion as well as in economic growth is immense. However, low uptake seems to impede the growth of the sector hence the need for a model that robustly predicts uptake of insurance among potential clients. In this research, we compared the performances of eight (8) machine learning models in predicting the uptake of insurance. The classifiers considered were Logistic Regression, Gaussian Naive Bayes, Support Vector Machines, K Nearest Neighbors, Decision Tree, Random Forest, Gradient Boosting Machines and Extreme Gradient boosting. The data used in the classification was from the 2016 Kenya FinAccess Household Survey. Comparison of performance was done for both upsampled and downsampled data due to data imbalance. For upsampled data, Random Forest classifier showed highest accuracy and precision compared to other classifiers but for down sampled data, gradient boosting was optimal. It is noteworthy that for both upsampled and downsampled data, tree-based classifiers were more robust than others in insurance uptake prediction. However, in spite of hyper-parameter optimization, the area under receiver operating characteristic curve remained highest for Random Forest as compared to other tree-based models. Also, the confusion matrix for Random Forest showed least false positives, and highest true positives hence could be construed as the most robust model for predicting the insurance uptake. Finally, the most important feature in predicting uptake was having a bank product hence bancassurance could be said to be a plausible channel of distribution of insurance products.

The objective of this work was to investigate the effect of different soil tillage practices in sunflower cultivation in a rotation system with intercropping Triticosecale x Pisum sativum. For this purpose a two year experimental field of 5% slope was established in central Greece. There were four treatments with three replications each. The treatments were: (a) no tillage - planting parallel to the contour (NTC-PAC), (b) conventional tillage - planting parallel to the contour (CTC-PAC), (c) no tillage - planting perpendicular to the contour (NTC-PEC), (d) conventional tillage - planting perpendicular to the contour (CTC-PEC). During the experiment plant height, leaf area index, specific leaf area, plants’ total nitrogen and plants’ proteins were measured. According to the results plant height ranged from 64.9 (CTC-PAC) to 85.2 cm (NTC-PEC) the 1st year and between 66.5 – 86.5 cm in CTC-PAC and NTC-PEC treatments in the 2nd year. Furthermore, LAI and SLA, plant’s total nitrogen and protein content and N-uptake were affected positively by the no tillage practice. To conclude, sunflower is a promising crop in a rotation system with intercropping Triticosecale x Pisum sativum, cultivating under rainfed sloping conditions.

Cadmium (Cd) is a toxic non–essential element to plants, and its accumulation in crops has significant adverse effects on human health. The cross–talk between copper (Cu) and Cd has been reported, but the molecular mechanisms remain unknown. Here, the function of wheat Cu transporter 3D (TaCOPT3D) in Cd tolerance was investigated. The TaCOPT3D transcripts significantly accumulated in wheat roots under Cd exposure. To test whether TaCOPT3D was involved in response to Cd stress, overexpressing lines with altered expression of TaCOPT3D transporters were compared to wild–type (WT) plants. The results showed that, under 20 μM Cd treatment, TaCOPT3D–overexpression lines exhibited more biomass and lower Cd accumulation in roots, shoots, and grains compared to WT plants. In addition, the TaCOPT3D–overexpression lines demonstrated less reactive oxygen species (ROS) and a greater amount of active antioxidant enzymes under Cd conditions than WT plants. Moreover, TaCOPT3D–overexpression lines highly reduced Cd accumulation under exposure to 20 μM Cu. The regulation pathway of TaCOPT3D in response to Cd stress was investigated, and transcription factor (TF) TaWRKY22, which targeted the TaCOPT3D promoter, was identified. Therefore, TaCOPT3D can serve as a candidate gene for decreasing Cd accumulation in wheat through genetic engineering.

Choline kinase inhibitors are an important class of cytotoxic compounds useful for the treatment of different forms of cancer since aberrant choline metabolism is a feature of neoplastic cells. Here we present the characterization and the structure activity relationship of a series of non-symmetrical choline kinase inhibitors characterized by a 3-aminophenol moiety, bound to 4-(dimethylamino)- or 4-(pyrrolidin-1-yl)pyridinium cationic heads through several linkers. These derivatives were evaluated both for their inhibitory activity on the enzyme and for their antiproliferative activity in a panel of six human tumor cell lines. The compounds with the best inhibitory results were those connected to the linker by the N-atom (4a-h) and these results are supported by docking studies. The compounds with the best antiproliferative results were those connected to the linker by the O-atom (3a-h). On the other hand, as was predictable in both families, the inhibitory effect on the enzyme is greater the shorter the length of the linker, while in tumor cells, lipophilicity and choline uptake inhibition could play a decisive role. Interestingly compounds 3c and 4f, selected for both their ability to inhibit the enzyme and good antiproliferative activity, are endowed with a low toxicity in non-tumoral cells (e.g human peripheral lymphocytes) respect to cancer cells. These compounds were also able to induce to induce apoptosis in Jurkat leukemic cells without causing significative variations of cell cycle. It is worth to mention that these derivatives, beside their inhibitory effect on choline kinase, displayed a modest ability to inhibit choline uptake thus suggesting that this mechanism may also contribute to the observed cytotoxicity.

Legumes are important sources of nitrogen and, therefore, the nitrogen fixing ability of the legume-rhizobia symbiosis has great potential to improve crop yields or reduce nitrogen fertilizer use. Unfortunately, legumes face serious and increasing threats of both biotic and abiotic stresses among which Fe-deficiency has been increased from past years. Fe nutrient deficiency limits pulse production and nitrogen fixation by specifically affecting any one of the four phases of legume-rhizobium symbiosis. Although Fe in soil is often present in adequate quantities, it is mainly present in insoluble Fe-(III) precipitates, limiting its uptake and utilization. The present review has focused on the iron nutrition and deficiency and probable uptake, transport and metabolism in legumes.

PrEP uptake in the Netherlands is growing but remains at suboptimal levels. Hence, the analysis of hurdles is paramount. Given the initial focus of PrEP provision among men-who-have-sex-with-men (MSM) via a demonstration project that was launched in June 2015, AmPrEP in Amsterdam, and pharmacies in the main urban areas (so called “Randstad”, entailing Amsterdam, Utrecht, Leiden, The Hague and Rotterdam), investigating regional differences is necessary. This study seeks to unravel regional differences jointly with psycho-social determinants of PrEP uptake. This cross-sectional study included 3,232 HIV-negative Dutch MSM recruited via the EMIS survey in late 2017. Prevalence and standardized prevalence ratio (SPR) of PrEP awareness, intention and uptake were measured on a regional level (Randstad vs. the rest of the country). Multilevel logistic modelling was conducted to identify the association of PrEP uptake with PrEP awareness and intention, sociodemographic, psycho-social determinants, and random effects from regional differences. MSM from the Randstad used more PrEP (SPR=1.4 vs. 0.7) compared to the rest of the country, but there were minor differences for awareness and intention. The regional distinction was estimated to explain 4.6% of the PrEP use variance. We observed a greater influence from PrEP intention (OR=4.5, 95%CI 2.0-10.1), while there was limited influence from the awareness of PrEP (OR=0.4, 95%CI 0.04-4.4). Lower education (OR=0.4, 95%CI 0.2-0.9) was negatively associated with PrEP uptake, however, no significant difference was found between middle and high education (OR=1.2, 95%CI 0.7-2.0). We showed that regional differences – MSM in non-urban regions – and other psycho-social determinants account for lower PrEP uptake. Based on these findings, more fine-tuned PrEP access with a focus on non-urban regions can be implemented, and tailored campaigns increasing intention/use can be conducted among target populations.

The prevalence of diabetes mellitus (DM), considered one of the most common metabolic disorders, has dramatically increased and resulted in higher rate of morbidity and mortality around the world, in the past decade. It is well known that insulin resistance in target tissues and a deficiency in insulin secretion from pancreatic β-cells are the main characteristic of type 2 diabetes. The aim of this study was the bio-evaluation of compounds isolated from three selected plant species; namely, Salvia africana-lutea, Leonotis ocymifolia and Plectranthus madagascariensis, for their glucose uptake ability. Methanolic extracts were produced from the arterial part of each plant. Compounds were identified using different spectroscopic techniques. The glucose uptake ability of each compound was then evaluated in mammalian cells using 2-deoxyglucose-6-phosphate. The cytotoxicity of each compound was established via the MTT assay. Chromatographic purification of the three plant species yielded fifteen pure terpenoids. Compounds 1 (p = 0.0031), 8 (p = 0.0053), and 6 (p = 0.0086), showed a marked increase in glucose uptake, with p values of p=0.0031, p=0.0053 and p=0.0086, respectively. Additionally, 1, 4 and 6 exhibited cytotoxicity toward mammalian tissue with a decrease in cell viability of ~70%, ~68% and ~67%, respectively. The results suggested that several compounds demonstrated a marked increase in glucose uptake while two of the compounds exhibited signs of cytotoxicity. It may, therefore, be suggested that these compounds be considered as potential candidates for novel plant-derived alternative therapies in the treatment of type 2 diabetes.

To close the nutrient-related yield gaps in maize, balanced nutrition using primary and secondary macronutrients as well as micronutrients is recommended. Multi-nutrient diagnostic field trials were conducted in Guinea Savanna of Nigeria to assess the interactive effects of macronutrients and micronutrients on maize grain yields, nutrient uptake as well as N, P and K use efficiencies. The treatments consisted of a control (zero fertilizer applied), an NPK treatment and 10 other treatments in which macronutrient (Mg, S) and/or micronutrients (B, and Zn) were added to the NPK. The experiment was laid out in Randomized Complete Block Design with 3 replications. Data collected were subjected to mixed model with nutrient management strategy as fixed effects while replication nested in location and interaction between location and nutrient management strategy as random effects. The results revealed significant effects (P < 0.05) of nutrient management strategy on maize yield, nutrient uptake and nutrient use efficiencies of N, P and K. The study revealed that yield advantage over the recommended NPK fertilizer as a result of application macronutrients and micronutrients were highest with Mg in Lere (2.4 t ha⁻¹), S + B + Zn in Faskari (2.8 t ha⁻¹), S + B in Doguwa (1.5 t ha⁻¹) and S + Zn in Toro (2.4 t ha⁻¹). Addition of Mg, S and B significantly increases macronutrient uptakes over the recommended NPK only. Agronomic use efficiency, internal utilization efficiency, apparent recovery efficiency and partial factor productivity were significantly increased with the addition of S, Mg, and B but were not improved with Zn application. It was concluded that nutrient limitations to maize in the Guinea Savanna go beyond N, P and K. This study recommends that S, Mg, and B are needed to improve maize productivity and engender improve the use efficiency of NPK fertilizers.

A field experiment was conducted in Ninghe, Tianjin, China, using 15N isotope method to evaluate the application of organic fertilizer on N distribution patterns of labelled and unlabeled N fertilizer, ammonium sulfate -15N uptake by rice, N use efficiency (NUE), and the fate of (15NH4)2SO4 applied. The experiment included eight treatments: CK-N (control + no-duck), CK-D (control + ducks), CF-N (chemical fertilizer + no-ducks), CF-D (chemical fertilizer + ducks), CM-N (chemical fertilizer + organic fertilizer + no-ducks), CM-D (chemical fertilizer + organic fertilizer + ducks), CD-N (chemical fertilizer 30% off + organic fertilizer + no-ducks), and CD-D (chemical fertilizer 30% off + organic fertilizer + ducks). The results showed that the application of organic fertilizer whether CM or CD significantly increased N and P concentrations over control (CK) and chemical fertilizer (CF). Moreover, no-significant differences were found in 15N fresh grain and husk concentration. Both organs ranged of 14.2-14.4 g kg-1 and 6.2-6.3 g kg-1, respectively. N derived from the fertilizer and soil significantly affected fresh grain compared to fresh husk. However, N uptake and N use efficiency did not show any differences. We concluded that organic fertilizer has a significant influence on rice growth and promote crop productivity.

Current education in biology is devoid of mathematics in many countries, probably because many relevant biological processes are explained from a qualitative point of view rather than addressing the quantitative aspects of these phenomena. Here, we employ a case study from the yeast physiology to illustrate the importance of numeracy skills for a deeper understanding of relevant biological problems. Yeast anaerobic growth on sugars is a widespread process as it is the basis for beer, bread, and winemaking and it is much akin to lactic acid fermentation in muscle cells in response to an increased energy demand. To study the physiology of yeasts under controlled conditions and being able to compare the results quantitatively, one ought to perform measurements and calculations involving concentrations of oxygen, biomass, and organic compounds. To set-up an “anaerobic” culture of Saccharomyces cerevisiae in a defined medium, one needs to calculate how much oxygen must enter the cultivation system, to meet the requirements for ergosterol and oleic acid biosyntheses, both of which require oxygen. Using basic physicochemical principles and simple mathematical skills, students will be able to compute the oxygen requirement for yeast growth under such “anaerobic” conditions.

The interaction between nanoparticles and cells has been studied extensively, but most research has focused on the effect of various nanoparticle characteristics, such as size, morphology, and surface charge, on the cellular uptake of nanoparticles. In contrast, there have been very few studies to assess the influence of cellular factors, such as growth factor responses, on the cellular uptake efficiency of nanoparticles. The aim of this study was to clarify the effects of epidermal growth factor (EGF) on the uptake efficiency of polystyrene nanoparticles (PS NPs) by A431 cells, a human carcinoma epithelial cell line. The results showed that EGF enhanced the uptake efficiency of A431 cells for PS NPs. In addition, inhibition and localization studies of PS NPs and EGF receptors (EGFRs) indicated that cellular uptake of PS NPs is related to the binding of EGF-EGFR complex and PS NPs. Different pathways are used to enter the cells depending on the presence or absence of EGF. In the presence of EGF, cellular uptake of PS NPs is via clathrin-mediated endocytosis, whereas in the absence of EGF, uptake of PS NPs does not involve clathrin-mediated endocytosis. Our findings indicate that EGF enhances cellular uptake of PS NPs by clathrin-mediated endocytosis. This result could be important for developing safe nanoparticles and their safe use in medical applications.

Gold nanoparticles have been indicated for use in a diagnostic and/or therapeutic role in several cancer types. The use of gold nanorods (AuNRs) with a surface plasmon resonance (SPR) in the second Near-Infrared II (NIR-II) optical window promises deeper anatomical penetration through increased maximum permissible exposure and lower optical attenuation. In this study, the targeting efficiency of anti-epidermal growth factor receptor (EGFR) antibody functionalised AuNRs with an SPR at 1064 nm was evaluated in vitro. Four cell lines, KYSE-30, CAL-27, Hep-G2 and MCF-7 that either over or under expressed EGFR were used. This expression was confirmed by flow cytometry and immunofluorescence. Cytotoxicity assays showed no AuNRs toxicity to both EGFR positive and EGFR negative cell lines up to a concentrations of 19 µg/ml. Optical microscopy demonstrated a significant difference (p&lt;0.0001) between targeted AuNRs (tAuNRs) and untargeted AuNRs (uAuNRs) in all four cancer cell lines. This study demonstrates that anti-EGFR functionalisation significantly increased the number of tAuNRs associated with each EGFR positive cancer cell. This successful targeting highlights the use of tAuNRs for molecular photoacoustic imaging or tumour treatment through plasmonic photothermal therapy.

Vaccine uptake is one of the indicators that has been used to guide immunization programs. This study aimed to evaluate whether the measles vaccine uptake is predicted by measles vaccine hesitancy. A community-based cross-sectional study was conducted in urban districts in Khartoum state in February 2019. Measles vaccine uptake among children was measured as either fully vaccinated or partially/not vaccinated. The Parents Attitude about Childhood Vaccination (PACV) scale was used to measure measles vaccine hesitancy. Multivariate logistic regression was run to identify the predictors of measles vaccination uptake controlling for sociodemographic variables and the adjusted odds ratios (aORs) with 95% CI were calculated. The receiver operator characteristic (ROC) curve was performed, besides area under the curve (AUC) for the PACV was computed. Data was collected from 495 participants. We found that measles vaccine hesitancy (PACV scores) predicted the uptake of measles vaccine after controlling other potential social confounders such as mother’s age and the number of children (aOR 1.055, 95% CI 1.028-1.028). Additionally, the ROC for the PACV yielded area under the curve (AUC 0.686 (95% CI 0.620-0.751, P <0.001). Our findings show that measles vaccine hesitancy in Sudan directly influences the uptake of the measles vaccine. Addressing the determinants of vaccine hesitancy through communication strategies will improve vaccine uptake.

Ferric uptake regulation protein is a repressor protein which binds an AT rich region of DNA (the iron box). Fur binds as a dimer in a helix turn helix mode and it is activated by iron(II) and other divalent transition metal ions at elevated concentrations in a process to regulate the ion uptake. Each transition metal ion induces certain conformational changes to aid the Fur binding, both the N-terminal and C-terminal domains take part in binding to DNA in addition to His 88 and His 86 residues. The process is discussed in view of experimental reports. Fe(II), Mn(II) and Co(II) activate Fur to bind DNA experimentally but Zinc plays a structural role and does not activate Fur to bind DNA.

COVID-19 vaccine hesitancy is considered responsible for the lower rate of acceptance of vaccines in many parts of the world. However, sources of this hesitancy are rooted in many social, political, and economic factors. This paper strives to find the most important variables in predicting the COVID-19 vaccination uptake. We introduce an explainable machine learning (ML) framework to understand the COVID-19 vaccination uptake around the world. To predict vaccination uptake, we have trained a random forest (RF) regression model using a number of sociodemographic and socioeconomic data. The traditional decision tree (DT) regression model is also implemented as the baseline model. We found that the RF model performed better than the DT model since RF is more robust to handle nonlinearity and multi-collinearity. Also, we have presented feature importance based on impurity measure, permutation, and Shapley values to provide the most significant unbiased features. It is found that electrification coverage and Gross Domestic Product are the strongest predictors for higher vaccination uptake, whereas the Fragile state index (FI) contributed to lower vaccination uptake. These findings suggest addressing issues that are found responsible for lower vaccination uptake to combat any future public health crisis.

Rhodovulum spp. are anoxygenic photosynthetic purple bacteria with versatile metabolisms, including the ability to obtain electrons from minerals in their environment to drive photosynthesis, a relatively novel process called phototrophic extracellular electron uptake (pEEU). Recently, our group isolated 15 strains of R. sulfidophilum to observe this metabolism in marine phototrophs. Our group previously observed carbon dioxide fixation coupled to phototrophic iron oxidation (photoferrotrophy) and pEEU in AB26 and identified a novel di-heme c¬-type cytochrome EeuP important for pEEU but not photoferrotrophy. Taxonomic re-evaluation based on 16S and pufM phylogenetic analyses led us to re-classify two isolates, AB26 and AB19, as Rhodovulum visakhapatnamense. The AB26 genome consists of 4,380,746 base-pairs, including two plasmids, and encodes 4,296 predicted protein-coding genes. AB26 contains 22 histidine kinases, 20 response regulators, and dedicates ~16% of its genome to transport. Transcriptomic data under aerobic, photoheterotrophy, photoautotrophy, and pEEU reveals how gene expression varies between metabolisms. Lastly, we use transcriptomic data for a comparative genomic analysis of potential pEEU-relevant genes between all 15 isolates. With these data we identify potential pEEU capable phototrophs within these isolates, and likely molecular mechanisms of pEEU.

Among the different ways to reduce the secondary effects of antineoplastic drugs in cancer treatment, the use of nanoparticles has demonstrated good results due to the protection of the drug and the possibility of releasing compounds to a specific therapeutic target. The α-isoform of folate receptor (FR) is overexpressed on a significant number of human cancers; therefore, folate-targeted crosslinked nanoparticles based on BSA and alginate mixtures and loaded with paclitaxel (PTX) have been prepared to maximizing the proven antineoplastic activity of the drug against solid tumors. Nanometric-range sized particles (169 ± 28nm - 296 ± 57nm), with negative Z-potential values (between -0.12 ± 0.04 and -94.1± 0.4), were synthesized. The loaded PTX (2.63±0.19 - 3.56 ±0.13 µg PTX/mg Np) was sustainably released along 23 and 27h. Three cell lines (MCF-7, MDA-MB-231 and HeLa) were selected to test the efficacy of the folate-targeted PTX-loaded BSA/ALG nanocarriers. The presence of FR on cell membrane led to a significant larger uptake of BSA/ALG-Fol nanoparticles regarding to the equivalent nanoparticles without folic acid on its surface. The cell viability results demonstrated a cytocompatibility of unloaded nanoparticle-Fol and a gradual decrease in cell viability after treatment with PTX-loaded nanoparticles-Fol due to the sustainable PTX release.

Mitochondrial Ca2+ ([Ca2+]M) uptake through Ca2+ uniporter (MCU) is central to many cell functions such as bioenergetics, spatiotemporal organization of Ca2+ signals, and apoptosis. MCU activity is regulated by several intrinsic proteins including MICU1, MICU2, and EMRE. While significant details about the role of MICU1, MICU2, and EMRE in MCU function have emerged recently, a key challenge for the future experiments is to investigate how these regulatory proteins modulate mitochondrial Ca2+ influx through MCU in intact cells under pathophysiological conditions. This is further complicated by the fact that several variables affecting MCU function change dynamically as cell functions. To overcome this void, we develop a data-driven model that closely replicates the behavior of MCU under a wide range of cytosolic Ca2+ ([Ca2+]C), [Ca2+]M, and mitochondrial membrane potential values in WT, MICU1 knockout (KO), and MICU2 KO cells at the single mitochondrion and whole-cell levels. The model is extended to investigate how MICU1 or MICU2 KO affect mitochondrial function. Moreover, we show how Ca2+ buffering proteins, the separation between mitochondrion and Ca2+-releasing stores, and the duration of Ca2+-releasing channels affect mitochondrial function under different conditions. Finally, we demonstrate an easy extension of the model to single channel function of MCU.

Soils are an important COS sink. However they can also act as sources of COS to the atmosphere. Here we demonstrate that variability in the soil COS sink and source strength is strongly linked to available soil inorganic nitrogen (N) content across a diverse range of biomes in Europe. We revealed in controlled laboratory experiments that N fertilisation simultaneously decreases the COS sink strength of soils while increasing the COS production rate. Furthermore, we found strong links between variations in the two gross COS fluxes, microbial biomass and nitrate and ammonium contents, providing new insights into the mechanisms involved. Our findings provide evidence for how soil-atmosphere exchange of COS is likely to vary spatially and temporally, a necessary step for constraining the role of soils and land use in the COS mass budget.

Inherent low soil fertility status limits productivity of rice in the lowland ecologies in Northern Ghana. Combining organic and inorganic N fertilizers could help to maintain the fertility of lowland soils for rice production. A screen house pot experiment was carried out to investigate the combined effect of biochar-compost and inorganic N fertilizer on the nitrogen uptake and agronomic performance of rice plants grown on Eutric Gleysol lowland soil. Inorganic N fertilizer alone and its combinations with different types of biochar-compost (based on the proportions of biochar and compost) were used as treatment. A control (unamended soil) was also included. The incorporation of biochar-compost and inorganic N fertilizer improved the growth parameters and yield components of rice plants. The combination of biochar-compost and inorganic nitrogen fertilizer was also found to improve nitrogen uptake and nutrient use efficiency (NUE) in rice plants. This practice could be the most likely viable option for alleviating lowlands soil fertility issues and increasing rice productivity in Northern Ghana.

Cyclodextrin polymers have high applicability in pharmaceutical formulations due to better biocompatibility, solubility enhancement, loading capacity and controlled drug release than parent the cyclodextrins. The cytotoxicity and cell uptake of new cationic beta-cyclodextrin monomers and polymers were evaluated as suitable material for nasal formulations and their protective effects on cells exposed to hydrogen peroxide were studied. PC12 and CACO-2 cells were selected as the neuronal and epithelial type cells, respectively, to mimic the structure of respiratory and olfactory epithelia of the nasal cavity. All cationic beta-cyclodextrin polymers tested showed dose- and time-dependent toxicity; nevertheless, at 5 µM concentration and 60 min of exposure, the quaternary-ammonium-beta-cyclodextrin soluble polymer could be recognized as non-toxic. Based on these results, fluorescently labelled quaternary-ammonium-beta-cyclodextrin monomer and polymer were selected for uptake studies in CACO-2 cells. The monomeric and polymeric beta-cyclodextrins were internalized in the cytoplasm of CACO-2 cells; the cationic monomer showed higher permeability than the hydroxypropyl-beta-cyclodextrin, employed as comparison. Therefore, these cationic beta-cyclodextrins showed potential as excipients able to improve the nasal absorption of drugs. Furthermore, amino-beta-cyclodextrin and beta-cyclodextrin soluble polymers were able to reduce oxidative damage in PC12 and CACO-2 cells and thus could be studied as bioactive carriers or potential drugs for cells protection against oxidative stress.

Mining activities could produce a large volume of spoils, waste rocks, and tailings, which are usually deposited at the surface and become sources of metal pollution. Phytostabilization of the mine spoils could limit the spread of these heavy metals. Phytostabilization can be enhanced by using soil amendments like manure-based biochar capable of immobilizing metal(loid)s when combined with plant species that are tolerant of high levels of contaminants while simultaneously improving properties of mine soils. However, the use of manure-based biochar and other organic amendments for mine spoil remediation are still unclear. In this greenhouse study, we evaluated the interactive effect of biochar application and compost on shoots biomass yield (SBY), roots biomass yield (RBY), uptake, and bioconcentration factor (BCF) of Zn and Cd in corn (Zea mays L.) grown in mine soil. Biochar sources (BS) consisted of beef cattle manure (BCM); poultry litter (PL); and lodge pole pine (LPP) were applied at 0, 2.5, and 5.0% (w/w) in combination with different rates (0, 2.5, and 5.0%, w/w) of cattle manure compost (CMC), respectively. Shoots and roots uptake of Cd and Zn were significantly affected by BS, CMC, and the interaction of BS and CMC. Corn plants that received 2.5% PL and 2.5% BCM had the greatest Cd and Zn shoot uptake, respectively. Corn plants with 5% BCM had the greatest Cd and Zn root uptake. When averaged across BS, the greatest BCF for Cd in the shoot of 92.3 was from the application BCM and the least BCF was from the application of PL (72.8). Our results suggest that incorporation of biochar enhanced phytostabilization of Cd and Zn with concentrations of water-soluble Cd and Zn lowest in soils amended with both manure-based biochars while improving biomass productivity of corn. Overall, phytostabilization technique and biochar application have the potential to be combined in the remediation of heavy metals polluted soils.

: Background: Overweight and obesity are major risk factors for many chronic diseases, and weight-loss interventions often include systematic exercising and nutritional supplements. The purpose of this study was to determine the independent/synergistic effects of Spirulina maxima supplementation (6-week, 4.5 g/day) and a systematic physical exercise program (6 weeks/ 2 times) on body composition and cardiorespiratory fitness of overweight and obese subjects. Methods: 27 overweight and 25 obese sedentary male subjects were assigned to four interventions through a randomized double-blind, crossover controlled trial: Physical exercise program with (SE) or without (Ex) Spirulina maxima or no-exercise program with (Sm) and without (C) Spirulina maxima. Body composition and cardiorespiratory fitness parameters were taken during a maximal intensity test. Results: As compared to C group, SE, Sm and Ex groups reduced (p < 0.05) their body fat percentage while improving their maximal oxygen uptake (VO₂max; r = −0.40), being obese subjects more benefited. Weight loss, time to reach fatigue and onset of blood lactate accumulation were improved in both Spirulina maxima supplemented groups, regardless the subjects’ body composition. Conclusions: Spirulina maxima supplementation synergistically improves the effects of systematic exercise in body composition and cardiorespiratory fitness parameters in overweight but mostly in obese adults.

Background: This study aimed to evaluate whether measles vaccine uptake can be predicted directly or indirectly by parental perceptions about the availability of measles vaccine services with parental hesitancy towards the measles vaccine as a potential mediator. Methods: This was a community-based cross-sectional study conducted at Omdurman locality in Khartoum state, Sudan in February 2019. The study population included parents/ guardians having at least one child aged 2 -3 years old. Mediation analysis was conducted using two models, the ordinary least squares path analysis and multiple logistic regression. Results: a total of 495 responded and the mean age of the mothers who participated in the study was 31.1 (SD=5.73). A half of the respondents (50.1%) completed university education and nearly three-quarters of the respondents (74.7%) were housewives. After controlling for the other factors, including the mother’s age and the number of children, parental perception about the accessibility and availability of the measles vaccine influences the uptake of the measles vaccine indirectly through the mediation effect of measles vaccine hesitancy. Conclusions: We suggest that intervening in measles vaccine hesitancy in addition to measles vaccination access issues will have positive impact on the uptake and coverage of the measles vaccine in Sudan.

Most smallscale farmers still use the traditional way of agricultural crop farming, and relay mostly use of chemical fertilizers (CF). Recently CF have become expensive and could in some way have a negative impact on soil quality after long term application. However, co-application of biogas slurry (BGS) with CF could help reduce farming costs while improving dry matter yields, grain yields, primary macronutrient uptake of (Nitrogen) N, (Phosphorus) P, (Potasium) K, (Calcium) Ca and (Magnesium) Mg and soil concentration of pH, (organic carbon) OC, N, P, K, Ca and Mg after crop harvest. The study was a field experiment conducted in 2016-2017 and 2017-2018 growing seasons. The field experiment was arranged in a randomized complete block design with four replicates. The treatments were based on percentages of recommended N rates of 120 kg N ha-1 for maize production. The BGS/CF treatments were (i) 0/0, (ii) 0/120, (iii) 24/96, (iv) 48/72, (v) 72/48, (vi) 96/24, (vii) 120/0 kg N ha-1. The spreading of the combination of BGS/CF treatments was performed by hand and incorporated into the top soil (0-10 cm) in each experimental plots. BGS/CF (48/72) treatment resulted into higher dry matter yield in 2016-2017, which was higher than all other treatment combinations, while in the 2017-2018 season, treatment of (0/120) resulted into higher dry matter than all other treatment combinations. The 48/72 and 0/120 treatments resulted into similar grain yield in 2016-2017 season which were higher than all other treatments. Treatments of 48/72, 72/48 and 120/0 had higher N, P, K, Ca and Mg uptake than 0/0, 0/120, 24/96 and 96/24 treatments in both seasons. Soil pH, total N, K, and Mg were high from the treatment of (120/0) than all other treatments in 2016-2017 while in the 2017-2018 season, treatment of (48/72) had higher OC, P and K after maize harvest. The findings of his study show that co-application of BGS/CF at 48/72 and 72/48 have maize yield benefits compared to the two resources, BGS/CF (120/0) and BGS/CF (0/120), applied separately in soil especially in the arid and semi-arid regions.

In the last 20 years, an increasing number of studies have been reported on membrane active peptides, which exert their biological activity by interacting with the cell membrane either to disrupt it and lead to cell lysis or to translocate through it to deliver cargos into the cell and reach their target. These peptides are attractive alternatives to currently used pharmaceuticals. Antimicrobial peptides (AMPs) and peptides designed for drug and gene delivery currently in the drug pipeline suggest that these membrane active peptides will soon constitute a significant percentage of the drug market. Here, we focus on two most prominent classes of membrane active peptides; AMPs and cell-penetrating peptides (CPPs). AMPs are a group of membrane active peptides that disrupt the membrane integrity or inhibit the cellular functions of bacteria, virus and fungi. CPPs are another group of membrane active peptides that mainly function as cargo-carriers even though they may also show antimicrobial activity to some extent. Biophysical techniques to understand how they interact with the membrane have shed light on the peptide–membrane interaction at various levels of detail. Structural investigation of membrane active peptides in the presence of the membrane provides important clues on the effect of the membrane environment on peptide conformations. Advances in live imaging techniques have allowed examination of peptide action at a single cell or single molecule level. In addition to these experimental biophysical techniques, molecular dynamics simulations provided clues on the peptide-lipid interactions and dynamics of the cell entry process at atomic detail. In this review, we summarize the recent advances in experimental and computational investigation of membrane active peptides with particular emphasis on two amphipathic membrane active peptides, the AMP melittin and the CPP pVEC.

Inflammation mediators enhance the activity of connexin (Cx) hemichannels especially in the epithelial and endothelial tissues. As potential release route for injury signals like (oligo)nucleotides, Cx hemichannels may contribute to long lasting inflammation. Specific inhibition of Cx hemichannels may therefore be a mode of prevention and treatment of long lasting, chronic sterile inflammation. The activity of Cx hemichannels was analysed in N2A and HeLa cells transfected with human Cx26 and Cx46 as well as in Calu-3 cells using the dye uptake as functional assay. Moreover, possible impact of the bioactive phenolic agents CVB2-61 and CVB4-57 on the barrier function of epithelial cells was analysed using Calu-3 cells. Both agents inhibited the dye uptake in N2A cells expressing Cx26 (> 5 µM) and Cx46 (> 20 µM). In Calu-3 cells, CVB2-61 and CVB4-57 reversible inhibited the dye uptake at concentrations as low as 5 µM, without affecting the gap junction communication and barrier function, even at concentrations of 20 µM. While CVB2-61 or CVB4-57 maintained a reduced dye uptake in Calu-3 cells, an enhancement of the dye uptake in response to stimulation of adenosine signaling was still observed after removal of the agents. The report shows that CVB2-61 and CVB4-57 reversible block Cx hemichannels. Deciphering the interaction mechanisms with Cx hemichannels could allow further development of phenolic compounds to target Cx hemichannels for a better and safer use in treatment of pathologies that involve Cx hemichannels.

The use of swine manure as a source of plant nutrients is one alternative to synthetic fertilizers. However, conventional manure application with >90% water and a low C:N ratio results in soil C loss to the atmosphere. Our hypothesis was to use biochar as a manure nutrient stabilizer that would slowly release nutrients to plants upon biochar-swine manure mixture application to soil. The objectives were to evaluate the impact of biochar-treated swine manure on soil total C, N, and plant-available macro and micronutrients in greenhouse-cultivated corn (Zea mays L.) and soybean (Glycine max (L.) Merr.). Neutral pH red oak (RO), highly alkaline autothermal corn stover (HAP), and mild acidic Fe-treated autothermal corn stover (HAPE) biomass were pyrolyzed to prepare biochars. Each biochar was surface-applied to swine manure at a 1:4 (biochar wt/manure wt) ratio to generate mixtures of manure and respective biochars (MRO, MHAP, and MHAPE). Conventional manure (M) control and manure-biochar mixtures were then applied to the soil at a recommended rate. Corn and soybean were grown under these controls and treatments (S, M, MRO, MHAP, and MHAPE) to evaluate the manure-biochar impact on soil quality, plant biomass yield, and nutrient uptake. Soil OM significantly (<0.05) increased in all manure-biochar treatments; however, no change in soil pH or N was observed under any treatment. No difference in soil ammonium between treatments was identified. There was a significant decrease in soil M3-P and soil NO₃^- for all manure-biochar treatments compared to the conventional M. However, the plant biomass nutrient concentrations were not significantly different from control manure. Moreover, an increasing trend of N and decreasing trend of P in the plant under all biochar-manure treatments than the controls were noted. This observation suggests that the presence of biochar is capable of influencing the soil N and P in such a way as not to lose those nutrients at the early growth stages of the plant. In general, no statistical difference in corn or soybean biomass yield and plant nutrient uptake for N, P, and K was observed. Interestingly, manure-biochar application to soil significantly diluted the M3-extractable soil Cu and Zn concentrations. The results attribute that manure-biochar has the potential to be a better soil amendment than conventional manure application to the soil.

The responses of the aromatic and medicinal plant Salvia sclarea (clary sage) to 900 µM Zn exposure for 8 days in a hydroponic culture were investigated. The tolerance mechanisms under excess Zn exposure were assessed by changes in nutrient uptake, photosynthetic characteristics and leaf structure. The uptake and the distribution of Zn, as well as some essential nutrient elements such as: Ca, Mg, Fe, Mn and Cu, were examined by inductively coupled plasma mass spectrometry (ICP-MS). The results revealed that Salvia sclarea is a Zn accumulator plant that tolerates significantly high toxic levels of Zn in the leaves by increasing the leaf content of Fe, Ca and Mn ions to protect the photosynthetic function and even stimulate photosystem I (PSI) and photosystem II (PSII) activities. Additionally, the leaf photosynthetic pigments and the total phenolic and anthocyanin content were also studied. Data showed that the exposure to excess Zn significantly increases the synthesis of phenolic compounds in the leaves which plays an important role in the Zn detoxification and protection against oxidative stress. Lipid peroxidation and electrolyte leakage in leaves used as clear indicators for heavy metal damage were slightly increased. All these data highlight that Salvia sclarea is an economically interesting plant for phytoextraction and/or phytostabilization of Zn contaminated soils.

In this study, we evaluated chlorophyll fluorescence (CF) under two extreme illumination conditions at plant scale with a passive spectroradiometer. Fluorescence (F) was estimated by reading directly from radiance spectra of a variety of plants illuminated with light-emitting diode (LED) grow lights in the laboratory. Solar-induced fluorescence (SIF) was estimated from spectral measurements of the same plants under sunlight using the Fraunhofer Line Depth (FLD) method. Chlorophyll fluorescence yield (F_yield) and solar-induced fluorescence yield (SIF_yield) were calculated by normalizing F and SIF with absorbed photosynthetically active radiation (APAR). Two approaches to estimating APAR were compared: utilizing white reference spectra and reflected spectra versus white reference spectra combined with the fraction of absorbed photosynthetically active radiation (fPAR) derived from literature. Average F and SIF were different by a factor of approximately twenty-four (F = 0.110 ± 0.038 Wm⁻²μm⁻¹sr⁻¹ versus SIF = 2.60 ± 1.87 Wm⁻²μm⁻¹sr⁻¹). In contrast, the average normalized values F_yield and SIF_yield were within the margin of error of one another (F_yield = 0.022 ± 0.008 μm⁻¹sr⁻¹ and SIF_yield = 0.030 ± 0.020 μm⁻¹sr⁻¹). This study highlights the influence of APAR on CF and the importance of properly accounting for it when estimating yield and demonstrates the ability of two simple and portable experimental setups with a passive instrument to obtain fluorescence metrics.

Myr47 lipopeptide consisting of hepatitis B virus (HBV) pre-S1 domain (myristoylated 2-48 peptide) is a commercialized effective anti-HBV drug, preventing the interaction of HBV with sodium taurocholate cotransporting polypeptide (NTCP) on human hepatocytes, of which the activity requires both N-myristoylation residue and specific amino acid sequence. Meanwhile, we recently reported that Myr47 reduces the cellular uptake of HBV surface antigen (HBsAg, subviral particle of HBV) in the absence of NTCP expression (Somiya; et al. Virology 2016, 497, 23–32). In this study, we analyzed how Myr47 reduces the cellular uptake of lipid nanoparticles (including liposomes (LPs) and HBsAg) without NTCP expression. By using Myr47 mutants lacking the HBV infection inhibitory activity, they could reduce the cellular uptake of LPs in an N-myristoylation-dependent manner whereas in an amino acid sequence-independent manner. Moreover, Myr47 and its mutants could reduce the interaction of LPs with apolipoprotein E3 (ApoE3) in an N-myristoylation-dependent manner regardless of their amino acid sequences. From these results, N-myristoyl residue of lipopeptides generally could interfere the LPs/HBsAg-ApoE3 complex formation, thereby reducing the cellular uptake of LPs/HBsAg. When lipid nanoparticles are used as a DDS (drug delivery system) nanocarrier, the surface modification with lipopeptides may be a new method to inhibit unwanted cellular uptake of DDS nanocarriers by non-target cells.

Tailoring treatment in patients with Hodgkin lymphoma (HL) is paramount to maximize outcomes while avoiding unnecessary toxicity. We aimed to compare the performance of SUVmax reduction (ΔSUVmax%) versus Deauville score (DS) in assessing chemotherapy response in pediatric HL patients undergoing 18F-FDG PET-CT. Fifty-two patients with biopsy-proven HL (age 8-16 years) were enrolled at baseline, interim (after the 2nd or 3rd chemotherapy round), and post-therapy (upon completion of first-line chemotherapy) 18F-FDG PET-CT. Interim and post-therapy DS and ΔSUVmax% were compared as response predictors. Patients were classified as responders and non-responders based on 24-month clinical follow-up. Interim DS showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of 100%, 80.4%, 100%, 40% and 82.7%, respectively in predicting response. Post-therapy DS showed a sensitivity, specificity, PPV, NPV and accuracy of 66.7%, 97.8%, 95.7%, 80% and 94.2%. Interim ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 82.6%, 97.4%, 38.5% and 82.7%, with a 56.3% cutoff. Post-therapy ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 84.8%, 97.5%, 41.7% and 84.6%, with a 76.8% cutoff. Sensitivity, specificity (p<0.05) and NPV (p<0.01) were significantly higher using DS than ΔSUVmax%. In conclusion, DS can predict chemotherapy response better than ΔSUVmax% in pediatric HL patients.

Quantitative biomarkers derived from positron-emission tomography/computed tomography (PET/CT) have been suggested as prognostic variables in immune-checkpoint inhibitor (ICI) treated non-small cell lung cancer (NSCLC). As such data for first-line ICI therapy and especially for chemotherapy-ICI combinations are still scarce, we retrospectively evaluated baseline 18F-FDG-PET/CT of 85 consecutive patients receiving first-line pembrolizumab with chemotherapy (n=70) or as monotherapy (n=15). Maximum and mean standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis and bone marrow-/ spleen to liver ratio (BLR/SLR) were calculated. Kaplan-Meier analyses and Cox-regression models were used to assess progression-free/overall survival (PFS/OS) and their determinant variables. Multivariate selection for PFS/OS revealed MTV as most relevant PET/CT biomarker (p<0.001). Median PFS/OS were significantly longer in patients with MTV≤70mL versus >70mL (PFS: 10 months (M; 95% confidence interval 4-16) vs. 4M (3-5), p=0.001; OS: not reached vs. 10M (5-15), p=0.004). Disease control rate was 81% vs. 53% for MTV≤/>70mL (p=0.007). BLR ≤1.06 versus >1.06 was associated with better outcomes (PFS: 8M (4-13) vs. 4M (3-6), p=0.034; OS: 19M (12-/) vs. 6M (4-12), p=0.005). In patients with MTV>70mL, concomitant BLR≤1.06 indicated a better prognosis. Higher MTV is associated with inferior PFS/OS in first-line ICI treated NSCLC, with BLR allowing additional risk stratification.

Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. Circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women and who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: 37 elderly women were separated into an elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using 1H-NMR and also insulin-dependent tissue specific glucose uptake in skeletal muscle were assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the 22:6 docosahexaenoic acid percentage of the total long chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (P = 0.015). DHA/FA associated significantly to skeletal muscle GU (P = 0.031) and M-value in the OLM group only (P = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and that this association is significantly weakened in the offspring of obese mothers.

Cisplatin (CDDP), carboplatin (CP), and oxaliplatin (OXP) are three platinating agents clinically approved worldwide for use against a variety of cancers. They are canonically known as DNA damage inducers; however, that is only one of their mechanisms of cytotoxicity. CDDP mediates its effects through DNA damage-induced transcription inhibition and apoptotic signalling. In addition, CDDP targets the endoplasmic reticulum (ER) to induce ER-stress, the mitochondria via mitochondrial DNA damage leading to ROS production, and the plasma membrane and cytoskeletal components. CP acts in a similar fashion to CDDP by inducing DNA damage, mitochondrial damage, and ER stress. Additionally, CP is also able to upregulate micro-RNA activity, enhancing intrinsic apoptosis. OXP, on the other hand, at first induces damage to all the same targets as CDDP and CP, yet it is also capable of inducing immunogenic cell death via ER stress and can decrease ribosome biogenesis through its nucleolar effects. In this comprehensive review, we provide detailed mechanisms of action for the three platinating agents, going beyond their nuclear effects to include their cytoplasmic impact within cancer cells. In addition, we cover their current clinical use and limitations, including side effects and mechanisms of resistance.