Novel Single-Nucleotide Variants for Morpho-Physiological Traits Involved in Enhancing Drought Stress Tolerance in Barley.

Barley (Hordeum vulgare L.) thrives in the arid and semi-arid regions of the world; nevertheless, it suffers large grain yield losses due to drought stress. A panel of 426 lines of barley was evaluated in Egypt under deficit (DI) and full irrigation (FI) during the 2019 and 2020 growing seasons. Observations were recorded on the number of days to flowering (NDF), total chlorophyll content (CH), canopy temperature (CAN), grain filling duration (GFD), plant height (PH), and grain yield (Yield) under DI and FI. The lines were genotyped using the 9K Infinium iSelect single nucleotide polymorphisms (SNP) genotyping platform, which resulted in 6913 high-quality SNPs. In conjunction with the SNP markers, the phenotypic data were subjected to a genome-wide association scan (GWAS) using Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK). The GWAS results indicated that 36 SNPs were significantly associated with the studied traits under DI and FI. Furthermore, eight markers were significant and common across DI and FI water regimes, while 14 markers were uniquely associated with the studied traits under DI. Under DI and FI, three (11_10326, 11_20042, and 11_20170) and five (11_20099, 11_10326, 11_20840, 12_30298, and 11_20605) markers, respectively, had pleiotropic effect on at least two traits. Among the significant markers, 24 were annotated to known barley genes. Most of these genes were involved in plant responses to environmental stimuli such as drought. Overall, nine of the significant markers were previously reported, and 27 markers might be considered novel. Several markers identified in this study could enable the prediction of barley accessions with optimal agronomic performance under DI and FI.

Climate-smart agriculture practices influence weed density and diversity in cereal-based agri-food systems of western Indo-Gangetic plains.

Climate-smart agriculture (CSA)-based management practices are getting popular across South-Asia as an alternative to the conventional system for particular weed suppression, resources conservation and environmental quality. An 8-year study (2012-2013 to 2019-2020) was conducted to understand the shift in weed density and diversity under different CSA-based management practices called scenarios (Sc). These Sc involved: Sc1, conventional tillage (CT)-based rice-wheat system with flood irrigation (farmers' practice); Sc2, CT-rice, zero tillage (ZT)-wheat-mungbean with flood irrigation (partial CA-based); Sc3, ZT rice-wheat-mungbean with flood irrigation (partial CSA-based rice); Sc4, ZT maize-wheat-mungbean with flood irrigation (partial CSA-based maize); Sc5, ZT rice-wheat-mungbean with subsurface drip irrigation (full CSA-based rice); and Sc6, ZT maize-wheat-mungbean with subsurface drip irrigation (full CSA-based maize). The most abundant weed species were P. minor > A. arvensis > M. indicus > C. album and were favored by farmers' practice. However, CSA-based management practices suppressed these species and favored S. nigrum and R. dentatus and the effect of CSAPs was more evident in the long-term. Maximum total weed density was observed for Sc1, while minimum value was recorded under full CSA-based maize systems, where seven weed-species vanished, and P. minor density declined to 0.33 instead of 25.93 plant m-2 after 8-years of continuous cultivation. Full CSA-based maize-wheat system could be a promising alternative for the conveniently managed rice-wheat system in weed suppression in north-west India.

Critical evaluation of functional aspects of evaporation barriers through environmental and economics lens for evaporation suppression - A review on milestones from improved technologies.

Climate change models predict an increase in rainfall variability, leading to floods and drought events, hence intensifying the need for reservoirs. However, up to 50% of reservoirs' capacity is lost by evaporation, affecting their function of ensuring water availability and stability. Over decades biological, chemical and physical barriers "covers" were developed for inhibiting evaporation. Such barrier's efficiency and applicability are still a matter of discussion, given their economic efficiency, environmental consequences, and operational difficulties are accounted for. In this review, we discussed the efficiency, applicability, and environmental suitability of these covers. Compared to the physical covers, the chemical and biological solutions tend to be less efficient. However, the use of physical covers is multidisciplinary, involving climate, material, and hydrological sciences, and are more efficient. Among the physical covers, the use of suspended covers and free-floating elements decreases evaporation to the tune of 85 and 80.0%, respectively. However, the economic efficiency of free-floating elements remains an open question since all studies overlooked their water footprint (water used in the manufacturing process of these covers), which was found to be very high. The use of these covers decreases heat storage, gas exchange rate, and light availability that could adversely influence dissolved oxygen, water quality, aquatic organisms, and the water ecosystem's function. These ecological consequences have not yet been investigated. The exception is the suspended covers, which have had determinate effects on dissolved oxygen and algae growth. Due to light weight, floating elements' operation is unstable and vulnerable to move due to wind effects. Therefore, such covers must be engineered to increase their stability. Free-floating elements could provide a visible and scalable solution to evaporation suppression when considering their economic visibility, environmental effects, and stability against wind and wave effects under the field conditions. However, these covers can be viable only when water availability is the limiting factor in crop production. We found that studies at reservoir scale are highly limited, therefore, investigations at reservoirs' scale emphasizing ecological aspects, cover stability and cost efficiency, are urgently needed.

Phospholipid based self-nanoemulsifying self-nanosuspension (p-SNESNS) as a dual solubilization approach for development of formulation with diminished food effect: Fast/fed in vivo pharmacokinetics study in human.

The novel self- nanoemulsifying self-nanosuspension (SNESNS) combines the advantages of two efficient solubilization technologies; the nanoemulsion and the nanosuspension. The aim of this study is to test the efficiency of phospholipid based self-nanoemulsifying self-nanosuspension (p-SNESNS) formulation as a powerful tool to diminish the food effect on bioavailability of lurasidone hydrochloride as BCS Class II model drug. Phospholipid was incorporated into SNESNS to increase the solubilization power of the in-situ formed nanoemulsion and facilitate the dispersion of the in-situ formed nanosized drug particles. P-SNESNS was evaluated for particle size, Polydispersity index, in vitro dissolution and transmission electron microscopy (TEM). The drug amount dissolved after water dilution of LSD p-SNESNS was ~2 folds that dissolved after dilution of non-phospholipid SNESNS. The self-nanosuspension obtained by aqueous dilution of p-SNESNS kept the cubic morphology of LSD macroparticles. The high in vitro dissolution of LSD in the non-sink dissolution media (water and Phosphate buffer pH6.8) indicated that the p-SNESNS formulation had successfully increased the drug solubility irrespective of pH of the medium. The pharmacokinetics parameters of LSD p-SNESNS in humans were the same in both the fasted and fed states and were similar to those of LSD capsules in the fed state. Our results propose that p-SNESNS could be promising to increase patient compliance and drug efficiency of BCS class II antipsychotics by diminishing the food effect on their oral absorption and preventing the necessity to administer them with food.

Ferroquine and artesunate in African adults and children with Plasmodium falciparum malaria: a phase 2, multicentre, randomised, double-blind, dose-ranging, non-inferiority study.

BACKGROUND: Artemisinin-based combination therapies (ACTs) are the recommended first-line treatment for uncomplicated Plasmodium falciparum malaria. Ferroquine is a new combination partner for fast-acting ACTs such as artesunate. We aimed to assess different doses of ferroquine in combination with artesunate against uncomplicated P falciparum malaria in a heterogeneous population in Africa. METHODS: We did a phase 2, multicentre, parallel-group, double-blind, randomised, dose-ranging non-inferiority trial at eight African hospitals (two in Gabon, three in Burkina Faso, one in Benin, and two in Kenya). We recruited patients presenting with acute P falciparum monoinfection (1000-200,000 parasites per µL), and a central body temperature of at least 37·5°C or history of fever in the past 24 h. We assessed patients in two sequential cohorts: cohort 1 contained adults (bodyweight >50 kg) and adolescents (aged ≥14 years, >30 kg), and cohort 2 contained children (aged 2-13 years, 15-30 kg). We randomly assigned patients (1:1:1:1) to receive artesunate 4 mg/kg per day plus ferroquine 2 mg/kg, 4 mg/kg, or 6 mg/kg, given double-blind once per day for 3 days, or ferroquine monotherapy 4 mg/kg per day given single-blind (ie, allocation was only masked from the patient) once per day for 3 days. We did 14 patient visits (screening, 3 treatment days and 48 h post-treatment surveillance, a visit on day 7, then one follow-up visit per week until day 63). The primary endpoint was non-inferiority of treatment in terms of PCR-corrected cure rate against a reference value of 90%, with a 10% non-inferiority margin, assessed in patients treated without major protocol deviations for parasitologically confirmed malaria. We assessed safety in all treated patients. This study is registered with ClinicalTrials.gov, number NCT00988507, and is closed. FINDINGS: Between Oct 16, 2009, and Sept 22, 2010, we randomly assigned 326 eligible patients to treatment groups, with last follow-up visit on Dec 1, 2010. 284 patients (87%) were available for per-protocol analyses. At day 28, PCR-confirmed cure was noted in 68 (97%, 95% CI 90-100) of 70 patients treated with ferroquine 2 mg/kg plus artesunate, 73 (99%, 93-100) of 74 with ferroquine 4 mg/kg plus artesunate, 71 (99%, 93-100) of 72 with ferroquine 6 mg/kg plus artesunate, and 54 (79%, 68-88) of 68 with ferroquine 4 mg/kg monotherapy. The three dose groups of ferroquine plus artesunate met the non-inferiority hypothesis. The most common adverse events were headache in cohort 1 (30 [19%] of 162 patients) and worsening malaria in cohort 2 (23 [14%] of 164 patients); occurrences were similar between treatment groups. INTERPRETATION: Ferroquine combined with artesunate was associated with high cure rates and was safe at all doses tested, and could be a promising new drug combination for the treatment of P falciparum malaria. Ferroquine could also partner other drugs to establish a new generation of antimalarial combinations, especially in regions that have developed resistance to ACTs. FUNDING: Sanofi.

A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers.

BACKGROUND: Previous investigations indicate that methotrexate, an old anticancer drug, could be used at low doses to treat malaria. A phase I evaluation was conducted to assess the safety and pharmacokinetic profile of this drug in healthy adult male Kenyan volunteers. METHODS: Twenty five healthy adult volunteers were recruited and admitted to receive a 5 mg dose of methotrexate/day/5 days. Pharmacokinetics blood sampling was carried out at 2, 4, 6, 12 and 24 hours following each dose. Nausea, vomiting, oral ulcers and other adverse events were solicited during follow up of 42 days. RESULTS: The mean age of participants was 23.9 ± 3.3 years. Adherence to protocol was 100%. No grade 3 solicited adverse events were observed. However, one case of transiently elevated liver enzymes, and one serious adverse event (not related to the product) were reported. The maximum concentration (C(max)) was 160-200 nM and after 6 hours, the effective concentration (C(eff)) was <150 nM. CONCLUSION: Low-dose methotraxate had an acceptable safety profile. However, methotrexate blood levels did not reach the desirable C(eff) of 250-400-nM required to clear malaria infection in vivo. Further dose finding and safety studies are necessary to confirm suitability of this drug as an anti-malarial agent.