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AbstractThe objective of this study was to determine the share of nitrogen Agronomic Efficiency/Productivity components (recovery/uptake efficiency; RE × physiological/utilization efficiency; PE) in a common intercropping system (maize-bean) which until the current research, there is no information about it. A split plots arrangement based on the randomized complete block design (RCBD) with three replications, was carried out during two successive cropping years. The main plot factor consisted of sole cultivation of maize and bean, row intercropping with ratios including 50%:50% (1 row of maize: 1 row of bean), 67%:33% (2 rows of maize: 1 row of bean), and 33%: 67% (1 row of maize: 2 rows of bean). Application and non-application of nitrogen (N) fertilizer (55 kg ha−1) were assigned to the subplots. In both species, when NUE was calculated based on the seed yield, the N utilization efficiency (NUtE) was higher in all treatments compared with NUtE based on the dry matter yield. Under the conditions of N application, the ratio of 50:50 of bean: maize intercropped had higher N uptake efficiency (NUpE) for both species. Moreover, the ratio of 50:50 had the highest total land equivalent ratio (LER) based on the seed yield (1.10), the NUpE (2.30%), and NUE indices (1.98 kg kg−1 and 2.02 kg kg−1 based on the seed yield and the dry matter yield, respectively). The ratio of 50:50 of bean: maize intercropped having the highest efficiency indices, can be a lasting solution to reduce N application and losses, improving its uptake efficiency. Reducing the excessive use of chemical N fertilizer increases the productivity of this input in agroecosystems and reduces costs and health concerns. [ABSTRACT FROM AUTHOR]

Comparing the absorption and translocation efficiency of the nutrients in olive cultivars can lead to the selection of cultivars with higher efficiency. This research was conducted with the aim of comparing the uptake and translocation capacity in 20 olive cultivars (12 domestic and 8 foreign) in a commercial orchard on calcareous soil in a randomized complete block design. Except for copper (Cu), leaf concentration of other elements was within the optimal range. In ʻAmphesis,ʼ high translocation (5.28%) and in ʻAmigdalolia,' high uptake capacity (12.6) caused an increase in leaf phosphorus (P). Leaf K in all cultivars was higher than the deficiency limit (0.77%). In none of the cultivars, leaf sodium (Na) concentration was higher than the toxicity limit (0.2%), it accumulated in the root of ʻZard-Aliabadʼ and ʻShengeh,ʼ and reduced in their leaf. Leaf iron (Fe) concentration of all cultivars was in the sufficient range (>63 mg kg−1) and the highest was in ʻGorgan-Aʼ and ʻZardʼ and the lowest in ʻKazeroon,ʼ ʻArbequinaʼ and ʻMission.ʼ Although the leaf Cu in ʻAmphesisʼ (4.32 mg kg−1) and ʻArbequinaʼ (4.03 mg kg−1) was above the sufficient limit, in the rest of the cultivars it was below this critical limit. The highest leaf manganese (Mn) concentration (61.35 mg kg−1) and the highest Mn translocation percentage (84.59) were in ʻFeshomi.ʼ Among these cultivars, ʻAmphesisʼ was higher than others in terms of P, potassium (K), Cu and zinc (Zn) leaf concentrations and ʻAmigdalolia in terms of P, K and Zn, and in most cases the reason for this is the higher translocation efficiency. [ABSTRACT FROM AUTHOR]

This article presents the performance estimation of a single-stage vapor adsorption system employing various carbon-based adsorbents with ethanol refrigerant, coupled with a small-scale biomass-based heating unit for space cooling, refrigeration, and heat-pumping applications. A detailed parametric investigation highlights the effects of operating temperatures, and heat exchanger to adsorbent mass ratio on specific cooling energy (SCE), coefficient of performance (COP), uptake efficiency (ηu), and mass of adsorbent to combustion fuel (mad/mcf) to identify the suitable adsorbent and sorption bed designs for each application. The numerical findings reveal that the flat-finned tube (FFT) adsorber outperforms traditional-finned tube (TFT) and tube & shell-type (T&S) adsorbers, achieving 19% and 30% higher COP, respectively, with biomass carbon-ethanol pair. The H2-treated Maxsorb-III shows the greatest optimal cooling COP (0.73), followed by the biomass-carbon (0.72) for refrigeration and space cooling. For heat pumping applications, biomass carbon-ethanol achieves the highest heat pumping COP (1.84) at a desorption temperature of 90°C, surpassing H2-treated Maxsorb-III. Further, the biomass-derived activated carbon requires the lowest amount of adsorbent per unit mass of combustion fuel in the biomass heating unit. The present thermodynamic analysis is a precursor for optimization of the potential heat-exchanger geometries and operating parameters, with the high-performance carbon adsorbents. [ABSTRACT FROM AUTHOR]

In this study, we investigated the physiological and biochemical responses of Ulva species to variation in nutrient availability. Sampling was conducted at two sites on Jeju Island, Korea, namely, Handong, which is close to seven intensive land-based fish farms, and Hado, which has no apparent nearby nutrient sources. We examined the water column nutrient concentrations, nitrate reductase (NR) activity, nitrate uptake efficiency, tissue C, N, and P content, and stable isotope ratios of Ulva species. Water column NH4+, NO3− + NO2−, and PO43− concentrations were significantly higher at Handong than at Hado. NR activity and tissue N content of Ulva species were significantly higher at Handong than at Hado. Notably, nitrate uptake efficiency was inversely proportional to NR activity and tissue N content. The physiological and biochemical responses of Ulva species were closely related to dissolved inorganic nitrogen, which stimulates Ulva species to regulate growth. Additionally, the δ15N values of Ulva tissues at both sites were within the previously reported range for fresh groundwater. Therefore, the main nitrogen source for Ulva growth may be submerged groundwater with high nutrient concentrations. Our results provide invaluable information for estimating dissolved inorganic nitrogen levels in water, which may facilitate development of management policies. [ABSTRACT FROM AUTHOR]

Abstract Cell-penetrating peptides (CPPs) are short chains of amino acids that have shown remarkable potential to cross the cell membrane and deliver coupled therapeutic cargoes into cells. Designing and testing different CPPs to target specific cells or tissues is crucial to ensure high delivery efficiency and reduced toxicity. However, in vivo/in vitro testing of various CPPs can be both time-consuming and costly, which has led to interest in computational methodologies, such as Machine Learning (ML) approaches, as faster and cheaper methods for CPP design and uptake prediction. However, most ML models developed to date focus on classification rather than regression techniques, because of the lack of informative quantitative uptake values. To address these challenges, we developed POSEIDON, an open-access and up-to-date curated database that provides experimental quantitative uptake values for over 2,300 entries and physicochemical properties of 1,315 peptides. POSEIDON also offers physicochemical properties, such as cell line, cargo, and sequence, among others. By leveraging this database along with cell line genomic features, we processed a dataset of over 1,200 entries to develop an ML regression CPP uptake predictor. Our results demonstrated that POSEIDON accurately predicted peptide cell line uptake, achieving a Pearson correlation of 0.87, Spearman correlation of 0.88, and r2 score of 0.76, on an independent test set. With its comprehensive and novel dataset, along with its potent predictive capabilities, the POSEIDON database and its associated ML predictor signify a significant leap forward in CPP research and development. The POSEIDON database and ML Predictor are available for free and with a user-friendly interface at https://moreiralab.com/resources/poseidon/ , making them valuable resources for advancing research on CPP-related topics. Scientific Contribution Statement: Our research addresses the critical need for more efficient and cost-effective methodologies in Cell-Penetrating Peptide (CPP) research. We introduced POSEIDON, a comprehensive and freely accessible database that delivers quantitative uptake values for over 2,300 entries, along with detailed physicochemical profiles for 1,315 peptides. Recognizing the limitations of current Machine Learning (ML) models for CPP design, our work leveraged the rich dataset provided by POSEIDON to develop a highly accurate ML regression model for predicting CPP uptake. Graphical Abstract

Cell-penetrating peptides (CPPs) are short chains of amino acids that have shown remarkable potential to cross the cell membrane and deliver coupled therapeutic cargoes into cells. Designing and testing different CPPs to target specific cells or tissues is crucial to ensure high delivery efficiency and reduced toxicity. However, in vivo/in vitro testing of various CPPs can be both time-consuming and costly, which has led to interest in computational methodologies, such as Machine Learning (ML) approaches, as faster and cheaper methods for CPP design and uptake prediction. However, most ML models developed to date focus on classification rather than regression techniques, because of the lack of informative quantitative uptake values. To address these challenges, we developed POSEIDON, an open-access and up-to-date curated database that provides experimental quantitative uptake values for over 2,300 entries and physicochemical properties of 1,315 peptides. POSEIDON also offers physicochemical properties, such as cell line, cargo, and sequence, among others. By leveraging this database along with cell line genomic features, we processed a dataset of over 1,200 entries to develop an ML regression CPP uptake predictor. Our results demonstrated that POSEIDON accurately predicted peptide cell line uptake, achieving a Pearson correlation of 0.87, Spearman correlation of 0.88, and r2 score of 0.76, on an independent test set. With its comprehensive and novel dataset, along with its potent predictive capabilities, the POSEIDON database and its associated ML predictor signify a significant leap forward in CPP research and development. The POSEIDON database and ML Predictor are available for free and with a user-friendly interface at , making them valuable resources for advancing research on CPP-related topics. Scientific Contribution Statement: Our research addresses the critical need for more efficient and cost-effective methodologies in Cell-Penetrating Peptide (CPP) research. We introduced POSEIDON, a comprehensive and freely accessible database that delivers quantitative uptake values for over 2,300 entries, along with detailed physicochemical profiles for 1,315 peptides. Recognizing the limitations of current Machine Learning (ML) models for CPP design, our work leveraged the rich dataset provided by POSEIDON to develop a highly accurate ML regression model for predicting CPP uptake. [ABSTRACT FROM AUTHOR]

: In order to explore the copper absorption characteristics of Anodonta woodiana, this study was based on the juveniles with higher Cu absorption efficiency as the experimental subjects. Five concentration gradients (2.0, 1.0, 0.1, 0.01 and 0.005 mg·L-1) of aquatic Cu were set according to its 96 h-EC50 to the mussels and China Fisheries Water Quality Standard (GB11607-89). This exposure experiment was conducted for 24 h. The results showed that the Cu absorption efficiency increased rapidly with the increase of exposure concentration, and the highest value was (0.69±0.11) μg/(g·h) in 2.0 mg·L-1 exposure group. However, the Cu removal rate showed a general decreasing trend, in which the removal rate of 0.005 mg·L-1 exposure group was the highest 84.8%, and the removal rate of 1.0 mg·L-1 exposure group was the lowest 28.9%. In conclusion, the high Cu uptake efficiency of juvenile A. woodiana indicates that it has a very high application potential in the prevention and control of heavy metal Cu pollution in freshwater fishery waters and in the development of model organisms for monitoring and evaluating the environmental Cu pollution in freshwater fishery waters. [ABSTRACT FROM AUTHOR]

One of the strategies of using low-soluble P farctions in the soil is selection and cultivation of plants and varieties with high P uptake efficiency. According to the necessity of P uptake efficiency and effective mechanisms in commercial varieties of sugarcane knowledge, a pot experiment was carried out in greenhouse condition in Hakim Farabi Agro-Industry CO.. The treatments were P fertilizer (including: blank (P0), 125 (P50) and 250 (P100) kg ha-1 as triple superphosphate) and varieties of sugarcane (including: CP57-614, CP69-1062 and CP48-103) in three sampling times (including: 45, 90 and 130 days after planting) with three replications in factorial based on completely randomized design. In this study, P uptake, root length, specific root length, root to shoot ratio and P influx were evaluated at each sampling time. In low available P condition, the CP48 and the CP57 varieties able to uptake more P and then considered as efficient P varieties. However, CP69 has less ability to uptake of P in this condition. In this condition, CP48 variety, P uptake was increased by 13% and 45% compared to CP57 and CP69 varieties respectively. However, CP57 showed enhancement of P uptake up to 29% compared to CP69 variety. Phosphorus influx decreased in CP57 and CP69 varieties by 53% and 67% respectively with aging of sugarcane that the greatest decrease of influx was observed in CP69 variety. In the CP48 variety, P influx increased up to 66%, which can be an effective factor in more P uptake. Therefore, these differences in the ability of P uptake in sugarcane varieties and mechanisms affecting P uptake can improve the management of P fertilizer consumption especially in ratoon. [ABSTRACT FROM AUTHOR]

Recent discoveries show that fungi can take up environmental RNA, which can then silence fungal genes through environmental RNA interference. This discovery prompted the development of Spray-Induced Gene Silencing (SIGS) for plant disease management. In this study, we aimed to determine the efficacy of SIGS across a variety of eukaryotic microbes. We first examined the efficiency of RNA uptake in multiple pathogenic and non-pathogenic fungi, and an oomycete pathogen. We observed efficient double-stranded RNA (dsRNA) uptake in the fungal plant pathogens Botrytis cinerea, Sclerotinia sclerotiorum, Rhizoctonia solani, Aspergillus niger and Verticillium dahliae, but no uptake in Colletotrichum gloeosporioides, and weak uptake in a beneficial fungus, Trichoderma virens. For the oomycete plant pathogen, Phytophthora infestans, RNA uptake was limited and varied across different cell types and developmental stages. Topical application of dsRNA targeting virulence-related genes in pathogens with high RNA uptake efficiency significantly inhibited plant disease symptoms, whereas the application of dsRNA in pathogens with low RNA uptake efficiency did not suppress infection. Our results have revealed that dsRNA uptake efficiencies vary across eukaryotic microbe species and cell types. The success of SIGS for plant disease management can largely be determined by the pathogen's RNA uptake efficiency.

In this study, we investigated the physiological and biochemical responses of Ulva species to variation in nutrient availability. Sampling was conducted at two sites on Jeju Island, Korea, namely, Handong, which is close to seven intensive land-based fish farms, and Hado, which has no apparent nearby nutrient sources. We examined the water column nutrient concentrations, nitrate reductase (NR) activity, nitrate uptake efficiency, tissue C, N, and P content, and stable isotope ratios of Ulva species. Water column NH4+, NO3− + NO2−, and PO43− concentrations were significantly higher at Handong than at Hado. NR activity and tissue N content of Ulva species were significantly higher at Handong than at Hado. Notably, nitrate uptake efficiency was inversely proportional to NR activity and tissue N content. The physiological and biochemical responses of Ulva species were closely related to dissolved inorganic nitrogen, which stimulates Ulva species to regulate growth. Additionally, the δ15N values of Ulva tissues at both sites were within the previously reported range for fresh groundwater. Therefore, the main nitrogen source for Ulva growth may be submerged groundwater with high nutrient concentrations. Our results provide invaluable information for estimating dissolved inorganic nitrogen levels in water, which may facilitate development of management policies.

In the present investigation the adsorption behavior of methylene blue (MB) dye from aqueous solution onto untreated chinar leaves powder (CLP) and chinar leaves biochar (CLB) has been studied. To find out optimum conditions, adsorption process was carried out by varying different parameters such as contact time, adsorbent dose, concentration, temperature, salts, and pH. The equilibrium adsorption data were subjected to different popular isotherms (Langmuir, Freundlich, and Temkin) and kinetic models (pseudo-first order, pseudo-second order and intra-particle diffusion model). The thermodynamic study was also done on the adsorption process. The maximum monolayer adsorption capacities for MB dye onto given adsorbents are 1.53 mg/g (CLP) and 1.02 mg/g (CLB). Also the values of RL and n suggest favourable adsorption process of MB dye onto CLP and CLB adsorbents. The pseudo-second order kinetic model is best obeyed by both the mentioned adsorbents for MB dye adsorption with R2 value equal to 1. Thermodynamic study reveals that the adsorption process of MB dye is spontaneous, endothermic (CLB) and exothermic (CLP). At an equilibrium time of 20 min the uptake efficiency (> 99%) was recorded for both the low cost adsorbents (CLP and CLB) thus proved them fast and effective adsorbents for the removal of MB dye.

In the present investigation the adsorption behavior of methylene blue (MB) dye from aqueous solution onto untreated chinar leaves powder (CLP) and chinar leaves biochar (CLB) has been studied. To find out optimum conditions, adsorption process was carried out by varying different parameters such as contact time, adsorbent dose, concentration, temperature, salts, and pH. The equilibrium adsorption data were subjected to different popular isotherms (Langmuir, Freundlich, and Temkin) and kinetic models (pseudo-first order, pseudo-second order and intra-particle diffusion model). The thermodynamic study was also done on the adsorption process. The maximum monolayer adsorption capacities for MB dye onto given adsorbents are 1.53 mg/g (CLP) and 1.02 mg/g (CLB). Also the values of RL and n suggest favourable adsorption process of MB dye onto CLP and CLB adsorbents. The pseudo-second order kinetic model is best obeyed by both the mentioned adsorbents for MB dye adsorption with R² value equal to 1. Thermodynamic study reveals that the adsorption process of MB dye is spontaneous, endothermic (CLB) and exothermic (CLP). At an equilibrium time of 20 min the uptake efficiency (> 99%) was recorded for both the low cost adsorbents (CLP and CLB) thus proved them fast and effective adsorbents for the removal of MB dye. [ABSTRACT FROM AUTHOR]

Summary: Spray‐induced gene silencing (SIGS) is an innovative and eco‐friendly technology where topical application of pathogen gene‐targeting RNAs to plant material can enable disease control. SIGS applications remain limited because of the instability of RNA, which can be rapidly degraded when exposed to various environmental conditions. Inspired by the natural mechanism of cross‐kingdom RNAi through extracellular vesicle trafficking, we describe herein the use of artificial nanovesicles (AVs) for RNA encapsulation and control against the fungal pathogen, Botrytis cinerea. AVs were synthesized using three different cationic lipid formulations, DOTAP + PEG, DOTAP and DODMA, and examined for their ability to protect and deliver double stranded RNA (dsRNA). All three formulations enabled dsRNA delivery and uptake by B. cinerea. Further, encapsulating dsRNA in AVs provided strong protection from nuclease degradation and from removal by leaf washing. This improved stability led to prolonged RNAi‐mediated protection against B. cinerea both on pre‐ and post‐harvest plant material using AVs. Specifically, the AVs extended the protection duration conferred by dsRNA to 10 days on tomato and grape fruits and to 21 days on grape leaves. The results of this work demonstrate how AVs can be used as a new nanocarrier to overcome RNA instability in SIGS for crop protection. [ABSTRACT FROM AUTHOR]

To achieve the Paris climate target, deep emissions reductions have to be complemented with carbon dioxide removal (CDR). However, a portfolio of CDR options is necessary to reduce risks and potential negative side effects. Despite a large theoretical potential, ocean-based CDR such as ocean alkalinity enhancement (OAE) has been omitted in climate change mitigation scenarios so far. In this study, we provide a techno-economic assessment of large-scale OAE using hydrated lime (‘ocean liming’). We address key uncertainties that determine the overall cost of ocean liming (OL) such as the CO2 uptake efficiency per unit of material, distribution strategies avoiding carbonate precipitation which would compromise efficiency, and technology availability (e.g., solar calciners). We find that at economic costs of 130–295 $/tCO2 net-removed, ocean liming could be a competitive CDR option which could make a significant contribution towards the Paris climate target. As the techno-economic assessment identified no showstoppers, we argue for more research on ecosystem impacts, governance, monitoring, reporting, and verification, and technology development and assessment to determine whether ocean liming and other OAE should be considered as part of a broader CDR portfolio.

Spray-induced gene silencing (SIGS) presents a promising RNA interference (RNAi)-based crop protection strategy against eukaryotic phytopathogens. However, the application of SIGS faces challenges, such as the limited uptake of dsRNA by certain pathogens and the instability of dsRNA in the environment. This study introduces innovative biomimetic nanovesicles, called extracellular vesicle (EV) mimetic chimeric nanovesicles (ECNs), assembled from tomato leaf cell membranes and cationic sterosomes via the freeze-thaw method. Similar to the function of EVs in nucleic acid transport between cells, ECNs serve as a hybrid nanosystem to overcome the challenge of delivering exogenous dsRNA in Phytophthora infestans . When applied to SIGS, the superiority of ECNs in crop protection becomes more apparent, including high loading and protection of dsRNA, improved biosafety, and efficient internalization into pathogen and plant cells, all of which significantly enhance the efficacy of RNAi in preventing early infection of P. infestans to susceptible tomato plants. This study demonstrates that ECNs are promising RNA delivery vehicles and will promote the use of SIGS-based RNA pesticides in sustainable agricultural production.

Background: Silicon (Si) is a multiple stress attenuator element in plants, however more research is needed to elucidate the actions in the plants defense system with low nutrition of manganese (Mn) for a prolonged period, and the attenuation mechanisms involved in the effects of Mn deficiency on energy cane with high fiber content. Thus, the objective of this study was to evaluate whether Si reduces the oxidative stress of the energy cane grown in low Mn in nutrient solution, to mitigate the effects of Mn deficiency, improving enzymatic and non-enzymatic defense, uptake of Mn the plant growth. Methods: An experiment was carried out with pre-sprouted seedlings of Saccharum spontaneum L. in a 2 × 2 factorial scheme in five replications in which the plants were grown under sufficiency (20.5 μmol L−1) and deficiency (0.1 μmol L−1) of Mn combined with the absence and presence of Si (2.0 mmol L−1) for 160 days from the application of the treatments. The following parameters were evaluated: accumulation of Mn and Si, H2O2, MDA, activity of SOD and GPOX, total phenol content, pigments, and quantum efficiency of PSII. Results: Mn deficiency induced the oxidative stress for increase the H2O2 and MDA content in leaves of plants and reduce the activity of antioxidant enzymes and total phenols causing damage to quantum efficiency of photosystem II and pigment content. Si attenuated the effects of Mn deficiency even for a longer period of stress by reducing H2O2 (18%) and MDA (32%) content, and increased the Mn uptake efficiency (53%), SOD activity (23%), GPOX (76%), phenol contents, thus improving growth. Conclusions: The supply of Si promoted great nutritional and physiological improvements in energy cane with high fiber content in Mn deficiency. The results of this study propose the supply of Si via fertirrigation as a new sustainable strategy for energy cane cultivation in low Mn environments. [ABSTRACT FROM AUTHOR]

Nitrogen (N) is the mineral nutrient required in greater quantities by plants with deficiencies affecting crop production. Nitrate (NO3-) and ammonium (NH4+) are the inorganic N forms most readily available for plant uptake. We investigated the influence of ammonium and nitrate rates on growth, nutritional status, chlorophyll production, and nutritional efficiency in mahogany seedlings, grown in an Oxisol soil under greenhouse conditions. Treatments were five N rates (50, 100, 150, 200, and 400 mg dm−3 N) in ammonium and nitrate forms and control treatment (0 mg dm−3 N), in a factorial design with five replications. The plants were harvested for evaluation at 150 days after transplanting. N supply affected mahogany growth, mainly in the production of leaf tissue. The maximum economic efficiency of N rates for production of leaf tissue was around 190 mg dm−3 N. The ammonium supply enhanced leaf tissue production, with a 20% increase in leaf area and 15% in leaf dry matter compared to nitrate. Furthermore, the plants showed a preference for ammonium uptake in rates above 200 mg dm−3 N, which indicates that the preference for N form was dependent on the concentration of N in the soil. The ammonium supply enhanced nutritional status, mainly phosphorus, demonstrating high synergism on uptake of this nutrient. Conversely, a strong antagonism between nitrate and phosphorus uptake was observed. Thus, ammonium enhanced the growth and nutritional status of mahogany seedlings and must be prioritized in its fertilization. [ABSTRACT FROM AUTHOR]

Continuous nitrogen (N) deposition has raised concerns that temperate forest ecosystems shift from N limitation to progressing phosphorus (P) limitation under global change. According to the multiple resource limitation theory, this will not only influence P economy, but also reduce N uptake and use efficiencies of trees such that growth is equally limited by N and P. We used different global change scenarios including summer drought to test the prediction of this hypothesis for the N economy of European beech (Fagus sylvatica L.) saplings. Our study demonstrates that the N uptake efficiency (NUptakeE) of beech adjusts to soil N availability and stabilizes leaf and fine root N concentrations. By contrast, both efficiencies of N use were curtailed by increasing P limitation under elevated soil N. The photosynthetic N use efficiency (PNUE) was serially reduced with decreasing soil P availability and increasing foliar N:P ratios, while the N use efficiency (NUE) decreased with increasing fine root N:P ratios. Soil drought induced relative P deficiency alike and reduced NUptakeE, PNUE, and NUE independent from the soil N:P ratios. We conclude that not only N deposition but also increasing summer droughts might affect N:P ratios, thereby inducing P imbalances and affecting the N economy of European beech saplings under global change.

This study aims to investigate radiolabeled Cefpodoxime Proxetil loaded chitosan (CP–CS) nanoparticles as nuclear imaging infection agent to Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli). The encapsulation efficiency of Cefpodoxime Proxetil was found 82 ± 2%. CP and CP–CS nanoparticles were radiolabeled with Tc-99 m. The radiochemical purity of 99mTc–CP and 99mTc–CP–CS nanoparticles were determined by RTLC as 89 ± 3% and 94 ± 2% respectively. In vitro bindings of 99mTc–CP–CS nanoparticles to S. aureus and E. coli were found higher than 99mTc–CP bindings. [ABSTRACT FROM AUTHOR]

Establishment of nutrient management of citrus groves for high yield and superior crop quality is a need for efficient production. Limited phosphorus (P) availability of low fertility tropical soils in Brazil impairs citrus production since adequate P supply is important in the first years after field planting. Research has demonstrated that tree growth and fruit yield in response to P fertilization vary depending on rootstock varieties. Therefore, this study evaluated P uptake and redistribution by Pêra sweet orange on Rangpur lime or Cleopatra mandarin rootstocks initially grown in nutrient solution containing either deficient (0.005 mmol/L) or suficient(1.0 mmol/L) P levels. Each of these groups of plants was later half maintained in the deficient P whereas other half was changed to the suficient P solutions both labeled with 32P (14.8 MBq per 9.0 L pot). Plants were further grown for 50 days. Based on concentrations of P in plant parts derived from solution and P remobilized in plant, we observed that, despite variations on plant growth on different rootstocks, P taken up by those on Rangpur lime was superior confirming greater efficiency of nutrient uptake of this rootstock under a non mycorrhized condition. Estimates of P remobilized from plant reserve to young leaves suggested that the process was more marked for plants on Cleopatra mandarin irrespective to P treatments. These explained the fact that leaf visual symptoms of P deficiency are more frequent on trees on Cleopatra rootstock and presented the need to fine tune P fertilization recommendations.

Abstract Ulva ohnoi is a green macroalga with fast growth and high rates of nitrogen and phosphorus absorption. Recently, this species has been recorded in several places with record green tide formation in some of them. Using molecular tools, we herein report the first occurrence of this species in Brazil and demonstrate its potential for phytoremediation in typical environmental concentrations of Cd (0.625–15 µg L-1). Similarly, the effects of physicochemical parameters (salinity and temperature) on the toxicity and uptake efficiency of this species were evaluated. Molecular analysis of two sequences (1141 bp) obtained corroborates another 34 sequences for U. ohnoi obtained from GenBank. The addition of Cd in the medium affected photosynthetic parameters and reduced growth rate. U. ohnoi showed resistance to Cd when cultivated at 18 °C, S15 and 18–25 °C, S35, at concentrations between 0.625 and 2.5 μg. L-1 of Cd; yet, positive growth rate was maintained. Dose-dependent accumulation was observed in all combinations of factors used with a maximum value of 4.20 μg Cd per gram of dry seaweed at 15 μg. L-1 of Cd at 18 °C and S35. Maximum value of the concentration factor was 81.3 ± 1.1% of Cd added at the concentration of 0.625 μg. L-1 to S15 and 18 °C. Our results demonstrate the potential of using U. ohnoi in the phytoremediation of Cd in saltwater or brackish water. Highlights • Ulva ohnoi removes 81.3% of the Cd added. • Dose-dependent accumulation was observed in all factors and combinations used. • Positive GRs were observed at the lowest concentrations of Cd used. • Changes in parameters analyzed were observed at all concentrations of Cd used. [ABSTRACT FROM AUTHOR]

• Quantile regression was used to benchmark N productivity for potato crops. • The approach was also useful for analysing key components of N use efficiency. • It can provide un-bias treatment comparison and benchmarks for commercial crops. • Achievable recovery did not differ between methods of N application to potato. • Achievable N efficiencies of potato were comparable to other major crops. Sound nitrogen management seeks to ensure crop yield, quality and profit, while avoiding over-fertilization lead to excess reactive nitrogen entering the agro- ecosystem or under-fertilization leading to mining of soil organic matter. Here we advance a framework to compare crop nitrogen use efficiency (NUE) across genotypes, environments and management practices that accounts for the non-linearity between N supply and N uptake, and between N uptake and crop dry matter or yield. We used published data of potato dry matter production, yield, N uptake and N inputs to demonstrate the efficacy of simple frontier analysis to describe the upper limits of the first order components of nitrogen use efficiency. Using quantile regression, frontier curves were derived for the response of apparent nitrogen recovery to the rate of applied N and for the responses of crop dry matter and tuber yield (dry matter) to crop N uptake. The analysis captured the known higher NUE for tuber production of late relative to early maturing potato varieties. The maximum achievable apparent nitrogen recovery did not differ between N fertilization methods. Simple frontier analysis provides a practical approach to benchmark the nitrogen use efficiency of crops. This then allows valid comparison of treatments or commercial crops when there are differences in the amount of N applied or differences in crop dry matter accumulation. [ABSTRACT FROM AUTHOR]

While a severe decrease in phosphorus (P) availability is already taking place in a large number of ecosystems, drought and nitrogen (N) deposition will likely further decrease the availability of P under global change. Plants have developed physiological strategies to cope with decreasing P resources, but it is unclear how these strategies respond to elevated N deposition and summer droughts. We investigated the influence of N and P availability and soil drought on P uptake (H333PO4 feeding experiment) and use efficiencies in young Quercus calliprinos Webb. trees. We hypothesized that (H1) the expected increases in soil N:P ratios will increase the efficiencies of P uptake and use of oak saplings but will decrease the efficiencies of N uptake and use, whereas (H2) drought will affect P uptake efficiency more than N uptake efficiency. In confirmation of (H1) we found that a sharp increase of the soil N:P ratio from 4 to 42 g g-1 significantly increased the instantaneous 33P uptake efficiency (33PUptakeE) by five-fold and long-term P uptake efficiency (PUptakeE) by six-fold, while it decreased N uptake efficiency (NUptakeE) and N use efficiency (NUE). In contradiction to (H1), P use efficiency (PUE) did not respond to the simulated extended gradient of soil N:P ratios but remained relatively constant. (H2) was only partially confirmed as soil drought reduced PUptakeE by up to a fourth at high soil N:P ratios but had no significant effect on NUptakeE. As a consequence, increasing summer droughts may decrease the response of PUptakeE to increasing P limitation, which – in the absence of adjustments of the efficiency of P use – can aggravate growth reductions in this eastern Mediterranean tree species under global change. [ABSTRACT FROM AUTHOR]

Selenium (Se) biofortification via crops is one of the best strategies to elevate the daily Se intake in areas where soil Se levels are low. However, Se fertilizer recovery (SeFR) is low and most of the Se taken up accumulates in non‐harvested plant parts and returns to the soil with plant residues. A pot experiment with soil was undertaken to study the efficiency of inorganic Se (Na2SeO4) and Se‐enriched plant residues for biofortification, as well as to identify the bottlenecks in Se utilization by Brassica napus L. The soil was fertilized with Na2SeO4 (0 and 7 µg Se kg−1) or with Se in stem or leaf residues (0 and 7 µg Se kg−1). A treatment with autoclaved soil was included (0 and 7 µg kg−1 as Na2SeO4) to unravel the impact of microbial activity on Se uptake. The Se‐enriched plant residues produced a lower Se uptake efficiency (SeUPE) and SeFR than did inorganic Se, and soil autoclaving enhanced Se accumulation in the plants. The time required for decomposition seems to preclude crop residues as an alternative source of Se. Furthermore, B. napus had a limited capacity to accumulate Se in seeds. The study shows that the bottlenecks in Se biofortification appear to be its low bioavailability in soil and poor loading from the silique walls to seeds. Thus, improved Se translocation to seeds would be a useful breeding goal in B. napus to increase SeFR. [ABSTRACT FROM AUTHOR]

Efficient cashew plants in relation to nutrition may represent gains in growth and production, especially in low fertility soils. This study aimed to determine the accumulation, the uptake, transport, and utilization efficiencies in different cashew genotypes. Twelve genotypes were evaluated, 10 of the dwarf type, a common type, and a hybrid. The seedlings were grown in plastic pots filled out with organic substrate. Sixty days after sowing, the plants were collected for the determination of dry matter and macro and micronutrients concentrations. Nutrient accumulation in cashew follows the descending order: N > K > P > Mg > Ca > S > Fe > Mn > Cu > B > Zn. Overall, for all nutrients, plants from BRS 274 had the high accumulation and utilization efficiency; the CCP 06 and CCP 76 in uptake; and the CCP 76 and BRS 189 in transport. [ABSTRACT FROM AUTHOR]

Safety and the quality of products rely on proper cleanliness procedures and good manufacturing practices in the production environment. The use of swabs for the collection of samples from surfaces has been a common practice in industries, medicine and forensic studies. To accommodate these different purposes, many varieties of swabs have been introduced into the market, and it is important to assess the performance of these swabs before incorporating into an environmental monitoring procedure. The overall effectiveness of a swab is determined by two factors: the number of bacteria that a swab can uptake from a surface and the number of picked-up bacteria the swab can elute into a releasing buffer. This study evaluated the uptake efficiency and release efficiency of four different commercially available swabs: CleanFoam (Texwipes, USA), FLOQSwabs (Copan diagnostic Inc., USA), Hydraflock swabs (Puritan medical products, USA), and Cotton swabs. Cotton swabs showed the highest uptake efficiency (96.5 ± 1.9%), whereas CleanFoam swabs (57.9 ± 20.3%) showed the least. Both flocked (FLOQSwabs and Hydraflock) swabs showed over 80% uptake efficiency. Releasing efficiency of swabs was tested with eight different releasing buffers. Cotton swabs displayed the lowest release efficiency with most of the tested releasing buffers. When employed with Tris HEPES, Tris MOPS, Tris TAPS, FLOQSwabs, and Hydraflock swabs exhibited releasing efficiency of over 75%. The overall efficiency of the swabs was determined using TAPS as the releasing buffer and the values obtained were 80.4 ± 9.8%, 54.7 ± 16.9%, 35.0 ± 12.7% and 25.2 ± 6.9% for Hydraflock swabs, FLOQSwabs, Cotton swabs and Cleanfoam swabs, respectively. • Different swabs sampled microorganisms on surfaces with varying efficiencies. • Best overall performance obtained with Hydraflock swabs and TAPS as the release buffer. • Choice of releasing buffer had no significant effect. [ABSTRACT FROM AUTHOR]

Background: Cancer is the leading cause of death in human disease and is a major public health problem around the world. Exosomes are a promising cancer biomarker and therapy target. Recent evidence demonstrate that tumor cells could inhibit natural killer (NK) cells’ immune surveillance function by releasing exosomes into tumor microenvironment. The intercelluar uptake of tumor cell-derived exosomes by NK cells is vital for using these exosomes in tumor diagnose and therapy. We aimed to investigate the efficiency of NK cell uptake of tumor exosomes. Methods: Exosomes derived from different tumor cells, RAW264.7 cells and NK cells were labeled by fluorescent dye and co-cultured with NK cells. The uptake rates of NK cells were observed by fluorescence microscope and analyzed by flow cytometry. Results: NK cells could take up more exosomes from themselves and cell lines originating from bone marrow. Epithelial cell lines can take up more exosomes from epithelial cells. There was no significant difference in uptake efficiency between Jurkat cells and RAW264.7 cells by NK cells, indicating that maybe the origin other than species affects the efficiency of recipient cell uptake of exosomes. Different tumor cells derived exosomes had different uptake efficiency by NK cells. Conclusion: There is certain pattern of NK cells uptake tumor exosomes, which provide important insights on how tumors affect NK cells and develop appropriate countermeasures. In addition, it can be also helpful to select and design proper exosomes as a drug carrier in future.

Aims: As ammonium (NH4+) has been reported as the “preferred” mineral N source for sugarcane (Saccharum spp.), the predominant supply of NH4+ has been hypothesized as a means of increasing the 15N recovery and crop yield. We aimed to evaluate the 15N recovery by sugarcane as affected by 15N-NH4+ and 15N-NO3− addition.Methods: Under field conditions, 15N-labeled ammonium nitrate [labeling as 15NH4NO3 (15N-NH4+) and NH415NO3 (15N-NO3−)] and urea were surface-applied at a rate of 100 kg N ha−1. Under controlled conditions, sugarcane was grown in hydroponic medium (containing unlabeled N) until the maximum N demand period. Subsequently, plants received 15N-NH4+ or 15N-NO3− (as ammonium nitrate). Plants were then sampled at 1, 3, 7, and 15 d after fertilization (DAF) to estimate 15N recovery.Results: Under field conditions, the 15N recovery for urea was lower than that for ammonium nitrate, partly explained by ammonia volatilization, but there was no difference in N use efficiency between the two fertilizer N sources, as well as between 15N-NH4+ and 15N-NO3− supply. Under controlled conditions, however, 15N-NH4+ resulted in higher 15N recovery than 15N-NO3− until 7 DAF. Nevertheless, as 15N-NH4+ became depleted in the nutrient solution, 15N-NO3− was taken up more intensely by the crop. At 15 DAF, highest 15N recovery was detected in the roots and whole plant under 15N-NO3− supply.Conclusions: Although uptake of NH4+ is faster than NO3−, the so-called “preference” for NH4+ by the crop did not necessarily translate into higher 15N recovery. Therefore, we suggest that the term “preference” should be used with caution to avoid misinterpretation. [ABSTRACT FROM AUTHOR]

Permanent raised-bed is an alternative planting system for wheat (Triticum aestivum L.) in rain-fed areas. However, this system in monoculture conditions produces lower yields compared with wheat in rotation. Our objective was to estimate these yield differences as affected by nitrogen (N) use efficiency (NUE). Wheat in monoculture and in rotation with maize (Zea maysL.) was evaluated for eight years (2002–2009) with four N rates (0, 40, 80 or 120 kg ha−1). Yield response to N in monoculture was consistently lower than for wheat in rotation. Yield reduction in monoculture at low and high N rate was 81 and 99% attributed to NUE out of which 70 and 82% was due to the uptake efficiency (UPE) and 30 and 19% to the utilization efficiency (UTE), respectively. Total N uptake proved to be the parameter that needs to be improved to enhance wheat yield in monoculture. Abbreviations:NUE: nitrogen use efficiency; UPE: uptake efficiency; UTE: utilization efficiency; Ns: nitrogen supply; NDVI: normalized difference vegetation index [ABSTRACT FROM PUBLISHER]

Embora não seja considerado nutriente essencial às plantas, o Si é classificado como elemento benéfico ou útil, mas pode alterar a dinâmica nutricional das plantas. Objetivando comparar a eficiência nutricional de variedades de cafeeiro (Catuaí, Mundo Novo e Icatu) em resposta à adubação silicatada, realizou-se um experimento em blocos casualizados, com as três variedades de mudas em tubetes combinadas com seis doses de CaSiO3 (T0 = 0, T1 = 0,063, T2 = 0,125, T3 = 0,25, T4 = 0,5 e T5 = 1,0 g dm-3 de substrato). A variedade Icatu teve a maior eficiência de absorção (EA) de Cu, Zn, Fe e Si, maior eficiência de uso (EU) de N, K, Ca, B e Mn, não diferindo da Mundo Novo com relação aos nutrientes N, Ca e Mn, e maior eficiência de translocação (ET) de N, S, Zn e de Fe. A Catuaí teve maior EA de P, K, B e Mn, não diferindo da Mundo Novo com relação aos nutrientes P, K e Mn, maior EU para Mg, S, Cu, Zn, Fe e Si, provavelmente devido à melhor ET desses nutrientes, exceto para Fe e Si. A Mundo Novo foi mais eficiente na absorção de N, K, Ca, Mg, Mn e Si, teve maior EU de P e Mn e maior ET de K, Ca, B, Mn e Si.Silicon is classified as a beneficial nutrient and can improve the nutritional dynamics of plants, although it is not considered an essential nutrient for plants. In an experiment in a randomized block design, three coffee cultivars (Catuaí, Mundo Novo and Icatu) were planted in plastic tubes, combined with six doses of calcium silicate (T0=0, T1=0.063, T2=0.125, T3=0.25, T4=0.5 and T5=1.0 g dm-3 substrate), to compare the nutritional efficiency of the cultivars in response to silicon fertilization. Cultivar Icatu showed the higher uptake efficiency (UE) of Cu, Zn, Fe, and Si, and efficiency of use (EU) of N, K, Ca, B, and Mn, but the later did not differ from Mundo Novo cultivar (N, Ca, and Mn). The efficiency of translocation (ET) was higher for N, S, Zn, and Fe. For Catuaí the uptake efficiency of P, K, B, and Mn was higher, but did not differ from Mundo Novo for P, K, and Mn. The Catuai's s efficiency of use for Mg, S, Cu, Zn, Fe, and Si was higher, probably because of a better ET of these nutrients, with exception of Fe and Si. The cultivar Mundo Novo was the most efficient in N, K, Ca, Mg, Mn and Si uptake, had the higher EU of P and Mn, and the highest ET of K, Ca, B, Mn, and Si.

Nitrogen use efficiency (NUE) is of great interest to wheat ( Triticum aestivum L.) breeders because it addresses the daunting prospect of feeding the burgeoning population under the constraints of limited land resources and a warming climate. In this study, we evaluated a 56 entry panel of SRW breeding lines and cultivars from the eastern US wheat region in 2014 for NUE and related traits. The 56-entry block was grown at Lexington and Princeton, KY at two N rates (0 and 112 kg ha −1 ) in a complete factorial design. We measured normalized difference vegetative index (NDVI), biomass, harvest index, N harvest index, N uptake efficiency, N utilization efficiency, post-anthesis N uptake, N remobilization efficiency and overall NUE. Breeders usually apply high rates of N fertilizer to their plots in order to maximize genetic yield potential. Our study indicates that without screening breeding lines in low N environments concurrently, it will not be possible to identify high NUE genotypes. Post-anthesis N uptake, was highly correlated with yield (r = 0.79) under high N, but heritability of this trait was close to zero. Heritability of NUE, on the other hand was moderately high (h 2 = 0.65). Five breeding lines ranked within the top 10 for NUE in both low and high N environments. NDVI was found to be both heritable and highly correlated with yield across N environments (R 2 = 0.78). Genome wide association studies of NUE and related traits revealed QTL associated with NUE (chromosome 2B), uptake efficiency (chromosome1B) and utilization efficiency (chromosomes 1A and 3A). In accord with other studies, these QTL are of small effect and will likely only be useful in genomic selection as opposed to marker-assisted selection. [ABSTRACT FROM AUTHOR]

This study investigated how spring nitrogen (N) application affects N uptake and growth performance in tall bearded (TB) iris 'Immortality' (Iris germanica L.). Container-grown iris plants were treated with 0, 5, 10, 15, or 20 mm N from 15NH415NO3 through fertigation using a modified Hoagland's solution twice a week for 6 weeks in Spring 2013. Increasing N rate increased plant height, total plant dry weight (DW), and N content. Total N content was closely related to total plant DW. The allocation of N to different tissues followed a similar trend as the allocation of DW. In leaves, roots, and rhizomes, increasing N rate increased N uptake and decreased carbon (C) to N ratio (C/N ratio). Leaves were the major sink for N derived from fertilizer (NDFF). As N supply increased, DW accumulation in leaves increased, whereas DW accumulation in roots and rhizomes was unchanged. This indicates increasing N rate contributed more to leaf growth in spring. Nitrogen uptake efficiency (NupE) had a quadratic relationship with increasing N rate and was highest in the 10 mm N treatment, which indicates 10 mm was the optimal N rate for improving NupE in this study. [ABSTRACT FROM AUTHOR]

Cell penetrating peptides (CPPs) were developed as vehicles for efficient delivery of various molecules. An ideal CPP‐peptide should not display any toxicity against cancer cells as well as healthy cells and efficiently enter into the cell. Because of the cationic nature and the intrinsic vector capabilities, these peptides can cause cytotoxicity. One of the possible reasons for toxicity of CPPs is direct translocation and consequently, pore formation on the plasma membrane. In this study it was demonstrated that interaction of poly‐glutamate with CPP considerably reduced their cytotoxicity in A549 cell. This strategy could be useful for efficient drug delivery mediated by CPP. [ABSTRACT FROM AUTHOR]

The aim of this work was to compare Cr(III) and Cr(VI) removal kinetics from water by Pistia stratiotes and Salvinia herzogii. The accumulation in plant tissues and the effects of both Cr forms on plant growth were also evaluated. Plants were exposed to 2 and 6 mg L−1of Cr(III) or Cr(VI) during 30 days. At the end of the experiment, Cr(VI) removal percentages were significantly lower than those obtained for Cr(III) for both macrophytes. Cr(III) removal kinetics involved a fast and a slow component. The fast component was primarily responsible for Cr(III) removal while Cr(VI) removal kinetics involved only a slow process. Cr accumulated principally in the roots. In the Cr(VI) treatments a higher translocation from roots to aerial parts than in Cr(III) treatments was observed. Both macrophytes demonstrated a high ability to remove Cr(III) but not Cr(VI). Cr(III) inhibited the growth at the highest studied concentration of both macrophytes while Cr(VI) caused senescence. These results have important implications in the use of constructed wetlands for secondary industrial wastewater treatment. Common primary treatments of effluents containing Cr(VI) consists in its reduction to Cr(III). Cr(III) concentrations in these effluents are normally below the highest studied concentrations in this work. [ABSTRACT FROM PUBLISHER]

To obtain a comprehensive understanding of the main source and route of human exposure to polybrominated diphenyl ethers (PBDEs), the daily intake and uptakes through inhalation, ingestion, and dermal contact for Shanghai residents were estimated on the basis of the PBDE concentrations in the air obtained in the present study and previous data reported in the literature. The PBDE concentrations in the gas and particle phases collected in Shanghai were 0.99-57.5 and 0.1-234 pg/m, respectively. The contamination levels of PBDEs in the air in Shanghai were similar to or slightly lower than the data from other regions. The estimated total daily intakes of PBDEs through the three routes were 607 and 1,636 ng/day for children and adults, respectively, while they decreased to 63.0 and 93.1 ng/day when the uptake efficiency (which is the fraction of contaminants that reaches the systemic circulation) of PBDEs was added to calculation. The results showed that dust is the main source of human exposure to PBDEs when PBDE uptake efficiency was not considered. It accounted for 66.2-79.2 % of the total PBDE intake. However, food is the main source, which accounted for 66.6-75.1 %, when the uptake efficiency was added to calculation. Among the three routes, dermal contact (53.1-76.6 %) is the main pathway, whereas ingestion (84.7-92.9 %) is the main one when the uptake efficiency was considered. Furthermore, risk assessment showed that the PBDE exposure amount would not cause obvious non-cancer and cancer risks to local residents. [ABSTRACT FROM AUTHOR]

Spray-Induced Gene Silencing (SIGS) is an innovative and eco-friendly technology where topical application of pathogen gene-targeting RNAs to plant material can enable disease control. SIGS applications remain limited because of the instability of dsRNA, which can be rapidly degraded when exposed to various environmental conditions. Inspired by the natural mechanism of cross-kingdom RNAi through extracellular vesicle trafficking, we describe herein the use of artificial nanovesicles (AVs) for dsRNA encapsulation and control against the fungal pathogen, Botrytis cinerea . AVs were synthesized using three different cationic lipid formulations, DOTAP + PEG, DOTAP, and DODMA, and examined for their ability to protect and deliver dsRNA. All three formulations enabled dsRNA delivery and uptake by B. cinerea . Further, encapsulating dsRNA in AVs provided strong protection from nuclease degradation and from removal by leaf washing. This improved stability led to prolonged RNAi-mediated protection against B. cinerea both on pre- and post-harvest plant material using AVs. Specifically, the AVs extended the protection duration conferred by dsRNA to 10 days on tomato and grape fruits and to 21 days on grape leaves. The results of this work demonstrate how AVs can be used as a new nanocarrier to overcome dsRNA instability in SIGS for crop protection., Competing Interests: Conflict of interests The authors declare that they have no competing interests.

Cell-penetrating peptides (CPPs) have proven their potential as an efficient delivery system due to their intrinsic ability to traverse biological membranes and transport various cargoes into the cells. In the present study, we have identified novel natural protein-derived CPPs using an integrated ( in silico and experimental) approach. First, using bioinformatics approach, arginine-rich peptide segments were extracted from SwissProt proteins and their cell-penetrating properties were predicted. Finally, eight peptides were selected and their internalization was validated using experimental techniques. Laser scanning confocal microscopy and flow cytometry confirmed that seven out of eight peptides were internalized into live cells with varying efficiencies without significant cytotoxicity. Three peptides have shown higher internalization efficacy than TAT peptide, the most widely used CPP. Among these three peptides, one peptide (P8), derived from voltage-dependent L-type calcium channel subunit alpha-1D, was able to accumulate inside in a variety of cell types very efficiently through a rapid dose-dependent process. Further, experiments involving inhibition with various endocytic inhibitors along with co-localization studies indicate that the uptake mechanism of P8 is macropinocytosis, a fluid-phase endocytosis process. In addition, competitive inhibition with heparin revealed the involvement of cell-surface proteoglycans in P8 uptake. In summary, the present study provides evidence that an integrated in silico and experimental approach is an effective strategy for the identification of novel CPPs and CPPs identified in the present study have promising perspectives for future drug delivery applications. [ABSTRACT FROM AUTHOR]

The penetration of polar or badly soluble compounds through a cell membrane into live cells requires mechanical support or chemical helpers. Cell-penetrating peptides (CPPs) are very promising chemical helpers. Because of their low cytotoxicity and final degradation to amino acids, they are particularly favored in in vivo studies and for clinical applications. Clearly, the future of CPP research is bright; however, the required optimization studies for each drug require considerable individualized attention. Thus, CPPs are not the philosopher's stone. As of today, a large number of such transporter peptides with very different sequences have been identified. These have different uptake mechanisms and can transport different cargos. Intracellular concentrations of cargos can reach a low micromole range and are able to influence intracellular reactions. Internalized ribonucleic acids such as small interfering RNA (siRNA) and mimics of RNA such as peptide nucleic acids, morpholino nucleic acids, and triesters of oligonucleotides can influence transcription and translation. Despite the highly efficient internalization of antibodies, enzymes, and other protein factors, as well as siRNA and RNA mimics, the uptake and stabile insertion of DNA into the genome of the host cells remain substantially challenging. This review describes a wide array of differing CPPs, cargos, cell lines, and tissues. The application of CPPs is compared with electroporation, magnetofection, lipofection, viral vectors, dendrimers, and nanoparticles, including commercially available products. The limitations of CPPs include low cell and tissue selectivity of the first generation and the necessity for formation of fusion proteins, conjugates, or noncovalent complexes to different cargos and of cargo release from intracellular vesicles. Furthermore, the noncovalent complexes require a strong molar excess of CPPs, and extensive experimentation is required to determine the most optimal CPP for any given cargo and cell type. Yet to predict which CPP is optimal for any given target remains a complex question. More recently, there have been promising developments: the enhancement of cell specificity using activatable CPPs, specific transport into cell organelles by insertion of corresponding localization sequences, and the transport of drugs through blood-brain barriers, through the conjunctiva of eyes, skin, and into nerve cells. Proteins, siRNA, and mimics of oligonucleotides can be efficiently transported into cells and have been tested for treatment of certain diseases. The recent state of the art in CPP research is discussed together with the overall scope, limitations, and some recommendations for future research directions. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]