Effect of Gibberellic Acid and Mechanical Scarification on the Germination and Seedling Stages of Chenopodium quinoa Willd. under Salt Stress.

Quinoa (Chenopodium quinoa Willd.) is a facultative halophyte renowned for its importance in enhancing food security, and it supports forage production across diverse climatic regions. The objective of this study is to examine the impacts of multiple pre-treatment methods on C. quinoa seed (Titicaca cultivar) germination parameters, identify the optimum pre-treatment to diminish the consequence of salinity, and promote the productivity of this crop, especially in marginal environments. For this purpose, a spectrum of sodium chloride (NaCl) concentrations spanning from 0 to 500 mM and gibberellic acid (GA3) concentrations ranging from 0 to 300 ppm were tested, and mechanical scarification (MS) was carried out. The effect of a combination of these pretreatment NaCl/GA3 and NaCl/MS on the germination parameters of C. quinoa seed was also investigated. The results showed that the total germination, vigor index, and germination index decreased progressively with an increase in salinity. Hence, salinity exhibited a notable influence on most germination parameters. Moreover, seeds scarified with 500 mM of NaCl negatively affected all measured parameters. In contrast, gibberellic acid applied at 200 ppm was effective on most of the parameters measured, particularly under 100 mM of NaCl. These findings indicate that immersing seeds in gibberellic acid could mitigate the adverse impacts of salinity.

Chorematic modeling to represent dynamics in the quinoa agroecosystems in Peru.

Our research occurred in the Andean region, one of the eight global centers of domestication of plant species grown for agriculture. The shores of Lake Titicaca (located between Peru and Bolivia), at 3800 meters above sea level, are recognized as the center of origin of quinoa (Chenopodium quinoa Willd.). In this region, complex societies have emerged, thanks to the development of water and soil management technologies. They have managed to overcome high mountain territories' extreme and variable climatic conditions. These societies have traditionally protected and preserved quinoa as food for present and future generations through their long-standing knowledge and cultivation practices. The fieldwork occurred in the context of Andean family farming, and our study analyzes nature-society dynamics with a chorematic approach and interviews with local communities. The interest of this work is the transformation of the landscape at the scale of the mountain agroecosystem to understand better the impacts of rural development policies. Chorematic modeling was applied to two periods, before and after 1970, a pivotal year in Peru for agriculture, to show how socio-spatial dynamics in the Andean environment are changing, particularly concerning the evolution of quinoa cultivation. The results show that wild quinoa relatives' distribution is strongly linked to the socio-spatial organization of the agroecosystem. Different species of wild quinoa relatives are maintained by villagers for their multiple foods, medicinal and cultural uses in natural areas, grazed areas, on edge, and also within cultivated fields. However, this management is changing under the pressure of global issues related to the international quinoa market, whose requirements imply reducing the presence of wild relatives in cultivated fields.

Lung-to-Heart Nano-in-Micro Peptide Promotes Cardiac Recovery in a Pig Model of Chronic Heart Failure.

BACKGROUND: The lack of disease-modifying drugs is one of the major unmet needs in patients with heart failure (HF). Peptides are highly selective molecules with the potential to act directly on cardiomyocytes. However, a strategy for effective delivery of therapeutics to the heart is lacking. OBJECTIVES: In this study, the authors sought to assess tolerability and efficacy of an inhalable lung-to-heart nano-in-micro technology (LungToHeartNIM) for cardiac-specific targeting of a mimetic peptide (MP), a first-in-class for modulating impaired L-type calcium channel (LTCC) trafficking, in a clinically relevant porcine model of HF. METHODS: Heart failure with reduced ejection fraction (HFrEF) was induced in Göttingen minipigs by means of tachypacing over 6 weeks. In a setting of overt HFrEF (left ventricular ejection fraction [LVEF] 30% ± 8%), animals were randomized and treatment was started after 4 weeks of tachypacing. HFrEF animals inhaled either a dry powder composed of mannitol-based microparticles embedding biocompatible MP-loaded calcium phosphate nanoparticles (dpCaP-MP) or the LungToHeartNIM only (dpCaP without MP). Efficacy was evaluated with the use of echocardiography, invasive hemodynamics, and biomarker assessment. RESULTS: DpCaP-MP inhalation restored systolic function, as shown by an absolute LVEF increase over the treatment period of 17% ± 6%, while reversing cardiac remodeling and reducing pulmonary congestion. The effect was recapitulated ex vivo in cardiac myofibrils from treated HF animals. The treatment was well tolerated, and no adverse events occurred. CONCLUSIONS: The overall tolerability of LungToHeartNIM along with the beneficial effects of the LTCC modulator point toward a game-changing treatment for HFrEF patients, also demonstrating the effective delivery of a therapeutic peptide to the diseased heart.

Challenges and Perspectives for Integrating Quinoa into the Agri-Food System.

Quinoa is a highly nutritious and abiotic stress-tolerant crop that can be used to ensure food security for the rapidly growing world population under changing climate conditions. Various experiments, based on morphology, phenology, physiology, and yield-related attributes, are being conducted across the globe to check its adoptability under stressful environmental conditions. High weed infestation, early stand establishment, photoperiod sensitivity, loss of seed viability after harvest, and heat stress during its reproductive stage are major constraints to its cultivation. The presence of saponin on its outer surface is also a significant restriction to its local consumption. Scientists are using modern breeding programs, such as participatory approaches, to understand and define breeding goals to promote quinoa adaptation under marginalized conditions. Despite its rich nutritional value, there is still a need to create awareness among people and industries about its nutritional profile and potential for revenue generation. In the future, the breeding of the sweet and larger-grain quinoa varietals will be an option for avoiding the cleaning of saponins, but with the risk of having more pests in the field. There is also a need to focus on mechanized farming systems for the cultivation, harvesting, and processing of quinoa to facilitate and expand its cultivation and consumption across the globe, considering its high genetic diversity.

Worldwide Evaluations of Quinoa-Biodiversity and Food Security under Climate Change Pressures: Advances and Perspectives.

Quinoa (Chenopodium quinoa Willd [...].

Adaptation of Some Quinoa Genotypes (Chenopodium quinoa Willd.), Grown in a Saharan Climate in Algeria.

Agriculture in southern Algeria faces several challenges that hinder its development, including drought, high temperatures and the excessive salinity of soil and groundwater. The introduction of crops resistant to these factors is one of the solutions chosen to address these abiotic constraints. This research aimed to evaluate the behavior of quinoa (Chenopodium Quinoa Willd.) grown in the Ouargla region of southeastern Algeria. Five varieties of quinoa (Santa maria, Giza1, Amarilla Sacaca, Blanca de Junin and Kancolla) were tested at two sites that differed in terms of soil salinity (9.95 mS/cm and 0.85 mS/cm) during 2019 and 2020. A complete random block experimental design with four repetitions was used for the agronomic tests. Our results clearly show that higher grain yields were obtained at the high salinity site (site 1) compared to the low salinity site (site 2). However, plant height, grain yield per plant and harvest index differed between varieties and sites. In contrast, stem diameter was not greatly affected by salinity. The varieties that seem to be best adapted to the growing conditions of the Ouargla region are, in descending order: Santa Maria, Giza1, Amarilla Sacaca and Blanca de Junin. When testing quinoa in new environments, it is critical to adapt the cropping cycle of varieties to avoid very high temperatures. The choice to switch to winter cultivation instead of spring cultivation can be an essential criterion for success. The biogeographical approach conducted in this research opens up new perspectives for the adaptation and cultivation of quinoa outside its region of origin to satisfy the food security of the people of North Africa.

Irrigation Regimes and Nitrogen Rates as the Contributing Factors in Quinoa Yield to Increase Water and Nitrogen Efficiencies.

Sustainable field crop management has been considered to reach the food security issue due to global warming and water scarcity. The effect of deficit irrigation and nitrogen rates on quinoa yield is a challenging issue in those areas. In this regard, the interaction effects of different N rates (0, 125, 250, and 375 kg N ha-1) and irrigation regimes [full irrigation (FI) and deficit irrigation at 0.75 FI and 0.5 FI] on quinoa yield and water and nitrogen efficiencies were evaluated with a two-year field experiment. Increasing nitrogen fertilizer application levels from 250 to 375 kg N ha-1 under FI and deficit irrigation did not cause a significant difference in seed yield and the total dry matter of quinoa. Furthermore, 20% and 34% reductions were observed for nitrogen use efficiency (NUE) and nitrogen yield efficiency with the application of 375 kg N ha-1 compared with that obtained in 250 kg N ha-1 nitrogen fertilizer, respectively. Therefore, a Nitrogen application rate of 250 kg ha-1 and applying 0.75 FI is suggested as the optimum rate to reach the highest seed water use efficiency (0.7 kg m-3) and NUE (0.28 kg m-3) to gain 4.12 Mg ha-1 quinoa seed yield. Under non-limited water resource conditions, an FI and N application rate of 375 kg ha-1 could be used for higher seed yield; however, under water-deficit regimes, an N application rate of 250 kg ha-1 could be adequate. However, questions about which environmental factors impressively restricted the quinoa growth for optimizing the potential yield need further investigation.

Trends and Limits for Quinoa Production and Promotion in Pakistan.

Quinoa is known as a super food due to its extraordinary nutritional qualities and has the potential to ensure future global food and nutritional security. As a model plant with halophytic behavior, quinoa has potential to meet the challenges of climate change and salinization due to its capabilities for survival in harsh climatic conditions. The quinoa crop has received worldwide attention due to its adoption and production expanded in countries out of the native Andean region. Quinoa was introduced to Pakistan in 2009 and it is still a new crop in Pakistan. The first quinoa variety was registered in 2019, then afterward, its cultivation started on a larger scale. Weed pressure, terminal heat stress, stem lodging, bold grain size, and an unstructured market are the major challenges in the production and promotion of the crop. The potential of superior features of quinoa has not been fully explored and utilized. Hence, there is a need to acquire more diverse quinoa germplasm and to establish a strong breeding program to develop new lines with higher productivity and improved crop features for the Pakistan market. Mechanized production, processing practices, and a structured market are needed for further scaling of quinoa production in Pakistan. To achieve these objectives, there is a dire need to create an enabling environment for quinoa production and promotion through the involvement of policymakers, research institutions, farmers associations, and the private sector.

Impact of Cyclization and Methylation on Peptide Penetration through Droplet Interface Bilayers.

Cell-penetrating peptides enter cells via diverse mechanisms, such as endocytosis, active transport, or direct translocation. For the design of orally delivered cell-penetrating peptides, it is crucial to know the contribution of these different mechanisms. In particular, the ability of a peptide to translocate through a lipid bilayer remains a key parameter for the delivery of cargos. However, existing approaches used to assess translocation often provide discrepant results probably because they have different sensitivities to the distinct translocation mechanisms. Here, we focus on the passive permeation of a range of hydrophobic cyclic peptides inspired by somatostatin, a somatotropin release-inhibiting factor. Using droplet interface bilayers (DIB), we assess the passive membrane permeability of these peptides and study the impact of the peptide cyclization and backbone methylation on translocation rates. Cyclization systematically improved the permeability of the tested peptides while methylation did not. By studying the interaction of the peptides with the DIB interfaces, we found membrane insertion and peptide intrinsic diffusion to be two independent factors of permeability. Compared to the industrial gold standard Caco-2 and parallel artificial membrane permeability assay (PAMPA) models, DIBs provide intermediate membrane permeability values, closer to Caco-2. Even for conditions where Caco-2 and PAMPA are discrepant, the DIB approach also gives results closer to Caco-2. Thereupon, DIBs represent a robust alternative to the PAMPA approach for predicting the permeability of peptides, even if the latter present extremely small structural differences.

Quinoa Phenotyping Methodologies: An International Consensus.

Quinoa is a crop originating in the Andes but grown more widely and with the genetic potential for significant further expansion. Due to the phenotypic plasticity of quinoa, varieties need to be assessed across years and multiple locations. To improve comparability among field trials across the globe and to facilitate collaborations, components of the trials need to be kept consistent, including the type and methods of data collected. Here, an internationally open-access framework for phenotyping a wide range of quinoa features is proposed to facilitate the systematic agronomic, physiological and genetic characterization of quinoa for crop adaptation and improvement. Mature plant phenotyping is a central aspect of this paper, including detailed descriptions and the provision of phenotyping cards to facilitate consistency in data collection. High-throughput methods for multi-temporal phenotyping based on remote sensing technologies are described. Tools for higher-throughput post-harvest phenotyping of seeds are presented. A guideline for approaching quinoa field trials including the collection of environmental data and designing layouts with statistical robustness is suggested. To move towards developing resources for quinoa in line with major cereal crops, a database was created. The Quinoa Germinate Platform will serve as a central repository of data for quinoa researchers globally.

A Long Journey of CICA-17 Quinoa Variety to Salinity Conditions in Egypt: Mineral Concentration in the Seeds.

Quinoa may be a promising alternative solution for arid regions, and it is necessary to test yield and mineral accumulation in grains under different soil types. Field experiments with Chenopodium quinoa (cv. CICA-17) were performed in Egypt in non-saline (electrical conductivity, 1.9 dS m-1) and saline (20 dS m-1) soils. Thirty-four chemical elements were studied in these crops. Results show different yields and mineral accumulations in the grains. Potassium (K), P, Mg, Ca, Na, Mn, and Fe are the main elements occurring in the quinoa grains, but their concentrations change between both soil types. Besides, soil salinity induced changes in the mineral pattern distribution among the different grain organs. Sodium was detected in the pericarp but not in other tissues. Pericarp structure may be a shield to prevent sodium entry to the underlying tissues but not for chloride, increasing its content in saline conditions. Under saline conditions, yield decreased to near 47%, and grain sizes greater than 1.68 mm were unfavored. Quinoa may serve as a complementary crop in the marginal lands of Egypt. It has an excellent nutrition perspective due to its mineral content and has a high potential to adapt to semi-arid and arid environments.

Membrane determinants for the passive translocation of analytes through droplet interface bilayers.

Understanding how small molecules cross cell membranes is crucial to pharmaceutics. Several methods have been developed to evaluate such a process, but they need improvement since many false-positive candidates are often selected. Robust tools enabling rapid and reproducible screening can increase confidence on hits, and artificial membranes based on droplet interface bilayers (DIBs) offer this possibility. DIBs consist in the adhesion of two phospholipid-covered water-in-oil droplets which reproduce a bilayer. By having donor and acceptor droplets, the permeability of an analyte can be studied. However, the relevance of this system relies on the comprehension of how well the physical chemistry of the produced bilayer recapitulates the behavior of cell membranes. This information is missing, and we address it here. Taking small fluorophores as model analytes, we studied their permeation through DIBs made of a wide range of phospholipids. We found that both the phospholipid acyl chain and polar head affect permeability. Overall, these parameters impact the phospholipid shape and thereupon the membrane lateral pressure, which is a major factor modulating with permeability in our system. These results depend on the nature of the chosen oil. We thereupon identified relevant physical chemistry conditions that best mimic the compactness and subsequent permeability of biological membranes.

Long-term stability of insulin glulisine loaded nanoparticles formulated using an amphiphilic cyclodextrin and designed for intestinal delivery.

Long-term stability is one of the main challenges for translation of therapeutic proteins into commercially viable biopharmaceutical products. During processing and storage, proteins are susceptible to denaturation. The aim of this work was to evaluate the stability of amphiphilic cyclodextrin-based nanoparticles (NPs) containing insulin glulisine. The stability of the NP dispersion was systematically evaluated following storage at three different temperatures (4 °C, room temperature (RT) and 40 °C). While the colloidal parameters of the NPs in terms of size and zeta potential were maintained (109 ± 9 nm, polydispersity index 0.272, negative zeta potential -25 ± 3 mV), insulin degraded over 60 days during storage. To enhance the shelf life of the product and to circumvent the need for cold-chain maintenance, a lyophilized formulation containing insulin glulisine NPs (1.75 mg/mL of NPs) and 25 mg/mL trehalose was produced. The freeze-dried powder extended the stability of the product for up to 30 days at ambient temperature and 90 days at 4 °C (with 95% and >80% insulin recovery, respectively). Following intra-intestinal administration of the freeze-dried formulation, while no lowering of blood glucose was seen, insulin glulisine was detected in both portal and systemic blood indicating that potential exists for further development of the formulation to simultaneously achieve prolonged stability and therapeutic efficacy.

First adaptation of quinoa in the Bhutanese mountain agriculture systems.

Bhutan represents typical mountain agriculture farming systems with unique challenges. The agriculture production systems under environmental constraints are typical of small-scale agricultural subsistence systems related to family farming in the Himalayan Mountains with very low level of mechanization, numerous abiotic stresses influenced by climate and other socio-economic constraints. Quinoa was first introduced in 2015 through FAO's support to Bhutan as a new crop to enhance the food and nutritional security of the Bhutanese people. The main objective was to adapt this versatile crop to the local mountain agriculture conditions as a climate resilient crop for diversifying the farmer's traditional potato and maize based cropping systems. Ten quinoa varieties were evaluated at two different sites representing contrasted mountain agroecologies in Bhutan and were tested during the two agricultural campaigns 2016 and 2017. Yusipang (2600 masl) represents the cool temperate agroecological zone, and Lingmethang (640 masl) the dry subtropical agroecological zone. The sowing time differed depending on the growing season and elevation of the sites. Results indicate that quinoa can be successfully grown in Bhutan for the two different agroecological zones. The grain yields varied from 0.61 to 2.68 t.ha-1 in the high altitude areas where quinoa was seeded in spring and harvested in autumn season. The grain yield in the lower elevation ranged from 1.59 to 2.98 t.ha-1 where the crop was sown in autumn and harvested in winter season. Depending on genotypes' characteristics and agroecological zones, crop maturity significantly varied from 92 to 197 days with all genotypes maturing much earlier in the lower elevations where mean minimum and maximum temperatures during the growing season were higher. Quinoa is rapidly promoted across different agroecological contexts in the country as a new climate resilient and nutrient dense pseudo cereal to diversify the traditional existing cropping system with some necessary adjustments in sowing time, suitable varieties and crop management practices. To fast track the rapid promotion of this new crop in Bhutan, four varieties have been released in 2018. In just over three years, the cultivation of quinoa as a new cereal has been demonstrated and partially adapted to the maize and potato based traditional cropping systems under the Himalayan mountain agriculture. Quinoa is also being adapted to the rice based cropping system and rapidly promoted as an alternative food security crop in the current 12th Five Year national development plan of Bhutan. To rapidly promote quinoa cultivation, the Royal Government of Bhutan is supporting the supply of free quinoa seeds, cultivation technologies and milling machines to the rural communities. To promote the consumption and utilization of quinoa at national level, consumer awareness are created by preparing and serving local Bhutanese dishes from quinoa during local food fairs and farmer's field days. In addition, the Royal Government of Bhutan has included quinoa in the school feeding programme recognizing the high nutrient value of the crop for enhancing and securing the nutritional needs of the young children.

Silica-Coated Nanoparticles with a Core of Zinc, l-Arginine, and a Peptide Designed for Oral Delivery.

Nanoparticle constructs for oral peptide delivery at a minimum must protect and present the peptide at the small intestinal epithelium in order to achieve oral bioavailability. In a reproducible, scalable, surfactant-free process, a core was formed with insulin in ratios with two established excipients and stabilizers, zinc chloride and l-arginine. Cross-linking was achieved with silica, which formed an outer shell. The process was reproducible across several batches, and physicochemical characterization of a single batch was confirmed in two independent laboratories. The silica-coated nanoparticles (SiNPs) entrapped insulin with high entrapment efficiency, preserved its structure, and released it at a pH value present in the small intestine. The SiNP delivered insulin to the circulation and reduced plasma glucose in a rat jejunal instillation model. The delivery mechanism required residual l-arginine in the particle to act as a permeation enhancer for SiNP-released insulin in the jejunum. The synthetic process was varied in terms of ratios of zinc chloride and l-arginine in the core to entrap the glucagon-like peptide 1 analogue, exenatide, and bovine serum albumin. SiNP-delivered exenatide was also bioactive in mice to some extent following oral gavage. The process is the basis for a platform for oral peptide and protein delivery.

Bridging communities in the field of nanomedicine.

An early dialogue between nanomedicine developers and regulatory authorities are of utmost importance to anticipate quality and safety requirements for these innovative health products. In order to stimulate interactions between the various communities involved in a translation of nanomedicines to clinical applications, the European Commission's Joint Research Centre hosted a workshop titled "Bridging communities in the field of Nanomedicine" in Ispra/Italy on the 27th -28th September 2017. Experts from regulatory bodies, research institutions and industry came together to discuss the next generation of nanomedicines and their needs to obtain regulatory approval. The workshop participants came up with recommendations highlighting methodological gaps that should be addressed in ongoing projects addressing the regulatory science of nanomedicines. In addition, individual opinions of experts relevant to progress of the regulatory science in the field of nanomedicine were summarised in the format of a survey.

Nano-carriers for drug routeing - towards a new era.

The objective of this article is to propose a re-visiting of the paradigms of nano-carriers based drug routeing from an industrial viewpoint. The accumulation of drugs in specific body compartments after intravenous administration and the improvement of the oral bioavailability of peptides were taken as examples to propose an update of the translational framework preceding industrialisation. In addition to the recent advances on the biopharmacy of nano-carriers, the evolution of adjacent disciplines such as the biology of diseases, the chemistry of polymers, lipids and conjugates, the physico-chemistry of colloids and the assembling of materials at the nanoscale (referred to as microfluidics) are taken into account to consider new avenues in the applications of drug nano-carriers. The deeper integration of the properties of the drug and of the nano-carrier, in the specific context of the disease, advocates for product oriented programmes. At the same time, the advent of powerful collaborative digital tools makes possible the extension of the expertise spectrum. In this open-innovation framework, the Technology Readiness Levels (TRLs) of nano-carriers are proposed as a roadmap for the translational process from the Research stage to the Proof-of-Concept in human.

Physicochemical, pharmacokinetic and pharmacodynamic analyses of amphiphilic cyclodextrin-based nanoparticles designed to enhance intestinal delivery of insulin.

Due to excellent efficacy, low toxicity, and well-defined selectivity, development of new injectable peptides is increasing. However, the translation of these drugs into products for effective oral delivery has been restricted due to poor oral bioavailability. Nanoparticle (NP) formulations have potential to overcome the barriers to oral peptide delivery through protecting the payload and increasing bioavailability. This study describes the rational design, optimization and evaluation of a cyclodextrin-based NP entrapping insulin glulisine for intestinal administration. A cationic amphiphilic cyclodextrin (click propyl-amine cyclodextrin (CD)) was selected as the primary complexing agent for NP development. Following NP synthesis, in vitro characterization was performed. The insulin glulisine NPs exhibited an average size of 109 ±â€¯9 nm, low polydispersity index (0.272) negative zeta potential (-25 ±â€¯3 mV), high association efficiency (71.4 ±â€¯3.37%) and an insulin loading of 10.2%. In addition, the NPs exhibited colloidal stability in intestinal-biorelevant media (SIF, supplemented-SIF 1% (w/v) and FaSSIF-V2) for up to 4 h. Proteolysis studies indicated that the NPs conferred protection to the entrapped insulin relative to free insulin. In vivo rat jejunal instillation studies demonstrated that the NPs mediated systemic insulin absorption, accompanied by a decrease in blood glucose levels. The relative bioavailability of the instilled insulin (50 IU/kg) from the NP was 5.5% compared to subcutaneous administration of insulin solution (1 IU/kg). The pharmacodynamic and pharmacokinetic data indicate that this cyclodextrin-based formulation may have potential for further research as an oral insulin dosage form.