From Foxtail Millet Husk (Waste) to Bioactive Phenolic Extracts Using Deep Eutectic Solvent Extraction and Evaluation of Antioxidant, Acetylcholinesterase, and α-Glucosidase Inhibitory Activities

Foxtail millet husk (FMH) is generally removed and discarded during the first step of millet processing. This study aimed to optimize a method using deep eutectic solvents (DESs) combined with ultrasonic-assisted extraction (UAE) to extract phenols from FMH and to identify the phenolic compositions and evaluate the biological activities. The optimized DES comprised L-lactic acid and glycol with a 1:2 molar ratio by taking the total flavonoid content (TFC) and total phenolic content (TPC) as targets. The extraction parameters were optimized to maximize TFC and TPC, using the following settings: liquid-to-solid ratio of 25 mL/g, DES with water content of 15%, extraction time of 41 min and temperature of 51 °C, and ultrasonic power at 304 W. The optimized UAE-DES, which produced significantly higher TPC, TFC, antioxidant activity, α-glucosidase, and acetylcholinesterase inhibitory activities compared to conventional solvent extraction. Through UPLC–MS, 12 phenolic compounds were identified, with 1-O-p-coumaroylglycerol, apigenin-C-pentosyl-C-hexoside, and 1-O-feruloyl-3-O-p-coumaroylglycerol being the main phenolic components. 1-O-feruloyl-3-O-p-coumaroylglycerol and 3,7-dimethylquercetin were identified first in foxtail millet. Our results indicated that FMH could be exploited by UAE-DES extraction as a useful source of naturally derived antioxidants, along with acetylcholinesterase and α-glucosidase inhibitory activities

Enrichment and bioactivities of polyphenols of crude extract by deep eutectic solvent extraction from foxtail millet bran

The adsorption and desorption capabilities of eight types of macroporous adsorption resins (MARs) for polyphenols from foxtail millet bran (FMB) extract were investigated. The D101 resin demonstrated the highest adsorption and desorption capacity, followed by the AB-8, DM301 and ADS-17 resins. The reaction kinetics for the adsorption of FMB polyphenols onto MARs accorded with a pseudo-first-order model (R2 > 0.99), with an apparent adsorption rate constant (K) of 1.225 × 10−2 g/mg·min. The adsorption process of FMB polyphenols onto D101 resin could be best described with the Langmuir adsorption isotherm (R2 > 0.99). The phenolic fractions were separated using silica gel column chromatography, and their total phenolic content (TPC), antioxidant activity, total flavonoid content (TFC), anti-glycosylation activity and acetylcholinesterase and α-glucosidase inhibitory activities were compared. Fraction 4 had the highest abundance of phenolic compounds, with N′-p-coumaroyl-N″-feruloylspermidine (461.65 ± 0.79 μg/g) and N′,N″-di-feruloylspermidine (578.46 ± 2.56 μg/g) being the predominant phenolics, the best acetylcholinesterase inhibitory activity and anti-glycosylation activity. Fraction 5 contained the highest apigenin-C-dihexoside, and therefore showed the best performance of α-glucosidase inhibitory activity. Fractions 4 and 5 displayed high antioxidant, acetylcholinesterase inhibitory activity and anti-diabetic potential, indicating that these two fractions should be targeted for further high-value utilisation of free polyphenols from FMB

Green extraction of phenolic compounds from foxtail millet bran by ultrasonic-assisted deep eutectic solvent extraction: Optimization, comparison and bioactivities

An ultrasonic-assisted extraction (UAE) protocol using deep eutectic solvent (DES) was employed to extract phenolic compounds from foxtail millet bran (FMB). DES composed with betaine and glycerol in a 1:2 M ratio was selected basing on the total phenolic content (TPC) extraction yield, with the optimal extraction technology investigated using response surface methodology (RSM) with Box-Behnken design (BBD). The optimized process obtained was as follows: DESs with water content of 29 mL/100 mL, ultrasonic power at 247 W, extraction temperature of 61 °C, and extraction time of 31 min. The TPC of the extract was 7.80 ± 0.09 mg ferulic acid equivalent (FAE)/g under the optimum extraction conditions, with the result corresponding well with the model prediction. DES-based UAE produced higher total phenolics, total flavonoids, in vitro antioxidant activity and acetylcholinesterase inhibitory activity than the conventional solvent extraction. The phenolic extract from FMB with DES-based UAE was mainly composed of fifteen phenolic compounds, with p-coumaric acid, apigenin-C-dihexoside, and N′, N″-di-p-coumaroylspermidine being the predominant phenolic compounds. Additionally, 1-O-p-coumaroylglycerol was detected for the first time in FMB. The microstructure differences of the FMB samples following extraction were confirmed using scanning electron microscopy (SEM)

A reduced tillering trait shows small but important yield gains in dryland wheat production

Reducing the number of tillers per plant using a tiller inhibition (tin) gene has been considered as an important trait for wheat production in dryland environments. We used a spatial analysis approach with a daily time-step coupled radiation and transpiration efficiency model to simulate the impact of the reduced-tillering trait on wheat yield under different climate change scenarios across Australia's arable land. Our results show a small but consistent yield advantage of the reduced-tillering trait in the most water-limited environments both under current and likely future conditions. Our climate scenarios show that whilst elevated [CO2 ] (e[CO2 ]) alone might limit the area where the reduced-tillering trait is advantageous, the most likely climate scenario of e[CO2 ] combined with increased temperature and reduced rainfall consistently increased the area where restricted tillering has an advantage. Whilst long-term average yield advantages were small (ranged from 31 to 51 kg ha-1 yr-1 ), across large dryland areas the value is large (potential cost-benefits ranged from AUD 23 to 60 MIL yr-1 ). It seems therefore worthwhile to further explore this reduced-tillering trait in relation to a range of different environments and climates, because its benefits are likely to grow in future dry environments where wheat is grown around the world

Prevalence, risk factors and treatments for post-COVID-19 breathlessness: a systematic review and meta-analysis

Persistent breathlessness >28 days after acute COVID-19 infection has been identified as a highly debilitating post-COVID symptom. However, the prevalence, risk factors, mechanisms and treatments for post-COVID breathlessness remain poorly understood. We systematically searched PubMed and Embase for relevant studies published from 1 January 2020 to 1 November 2021 (PROSPERO registration number: CRD42021285733) and included 119 eligible papers. Random-effects meta-analysis of 42 872 patients with COVID-19 reported in 102 papers found an overall prevalence of post-COVID breathlessness of 26% (95% CI 23–29) when measuring the presence/absence of the symptom, and 41% (95% CI 34–48) when using Medical Research Council (MRC)/modified MRC dyspnoea scale. The pooled prevalence decreased significantly from 1–6 months to 7–12 months post-infection. Post-COVID breathlessness was more common in those with severe/critical acute infection, those who were hospitalised and females, and was less likely to be reported by patients in Asia than those in Europe or North America. Multiple pathophysiological mechanisms have been proposed (including deconditioning, restrictive/obstructive airflow limitation, systemic inflammation, impaired mental health), but the body of evidence remains inconclusive. Seven cohort studies and one randomised controlled trial suggested rehabilitation exercises may reduce post-COVID breathlessness. There is an urgent need for mechanistic research and development of interventions for the prevention and treatment of post-COVID breathlessness

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background: The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods: We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings: We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation: Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding: PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification. Funding: UK Research and Innovation and National Institute for Health Research