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Abstract Stevia rebaudiana (stevia) is a plant in the Asteraceae that contains several biologically active compounds including the antidiabetic diterpene glycosides (e.g. stevioside, rebaudioside and dulcoside) that can serve as zero-calorie sugar alternatives. In this study, an elicitation strategy was applied using 5% polyethylene glycol (PEG), sodium chloride (NaCl; 50 and 100 mM) and gibberellic acid (2.0 and 4.0 mg/L GA3) to investigate their effect on shoot morphogenesis, and the production of phenolics, flavonoids, total soluble sugars, proline and stevioside, as well as antioxidant activity, in shoot cultures of S. rebaudiana. Herewith, the media supplemented with 2 mg/L and 4 mg/L GA3 exhibited the highest shooting response (87% and 80%). The augmentation of lower concentrations of GA3 (2 mg/L) in combination with 6-benzylaminopurine (BAP) resulted in the maximum mean shoot length (11.1 cm). The addition of 100 mM NaCl salts to the media led to the highest observed total phenolics content (TPC; 4.11 mg/g-DW compared to the control 0.52 mg/g-DW), total flavonoids content (TFC; 1.26 mg/g-DW) and polyphenolics concentration (5.39 mg/g-DW) in shoots cultured. However, the maximum antioxidant activity (81.8%) was observed in shoots raised in media treated with 50 mM NaCl. The application of 2 mg/L of GA3 resulted in the highest accumulation of proline (0.99 μg/mL) as compared to controls (0.37 μg/mL). Maximum stevioside content (71 µL/mL) was observed in cultures supplemented with 100 mM NaCl and 5% PEG, followed by the 4 mg/L GA3 treatment (70 µL/mL) as compared to control (60 µL/mL). Positive correlation was observed between GA3 and stevioside content. Notably, these two compounds are derived from a shared biochemical pathway. These results suggest that elicitation is an effective option to enhance the accumulation of steviosides and other metabolites and provides the groundwork for future industrial scale production using bioreactors.

Abstract Globally, salinity is an important abiotic stress in agriculture. It induced oxidative stress and nutritional imbalance in plants, resulting in poor crop productivity. Applying silicon (Si) can improve the uptake of macronutrients. On the other hand, using biochar as a soil amendment can also decrease salinity stress due to its high porosity, cation exchange capacity, and water-holding capacity. That’s why the current experiment was conducted with novelty to explore the impact of silicon nanoparticle-based biochar (Si-BC) on wheat cultivated on salt-affected soil. There were 3 levels of Si-BC, i.e., control (0), 1% Si-BC1, and 2.5% Si-BC2 applied in 3 replicates under 0 and 200 mM NaCl following a completely randomized design. Results showed that treatment 2.5% Si-BC2 performed significantly better for the enhancement in shoot and root length, shoot and root fresh weight, shoot and root dry weight, number of leaves, number of tillers, number of spikelets, spike length, spike fresh and dry weight compared to control under no stress and salinity stress (200 mM NaCl). A significant enhancement in chlorophyll a (~ 18%), chlorophyll b (~ 22%), total chlorophyll (~ 20%), carotenoid (~ 60%), relative water contents (~ 58%) also signified the effectiveness of treatment 2.5% Si-BC2 than control under 200 mM NaCl. In conclusion, treatment 2.5% Si-BC2 can potentially mitigate the salinity stress in wheat by regulating antioxidants and improving N, K concentration, and gas exchange attributes while decreasing Na and Cl concentration and electrolyte leakage. More investigations at the field level are recommended for the declaration of treatment 2.5% Si-BC2 as the best amendment for alleviating salinity stress in different crops under variable climatic conditions.

Abstract Soil salinity, the second most prominent cause of land degradation after soil erosion, has posed a persistent challenge to agriculture. Currently, approximately 1 billion hectares of Earth's land surface, equivalent to 7%, are affected by salinity. While biochar has proven effective in mitigating salinity stress, the specific role of deashed biochar in salinity mitigation has not been thoroughly explored. Therefore, this study was conducted to investigate the impact of four levels of deashed biochar (0%, 0.4%, 0.8%, and 1.2%) on the growth and physiological attributes of Fenugreek under both non-saline conditions (2.54 dS/m EC) and salinity stress conditions (5.46 dS/m EC). The results revealed a notable enhancement in various parameters under salinity stress. Compared to the control, the application of 1.20% deashed biochar led to a significant increase in shoot fresh weight (30.82%), root fresh weight (13.06%), shoot dry weight (17.43%), root dry weight (33.44%), shoot length (23.09%), and root length (52.39%) under salinity stress. Furthermore, improvements in internal CO2 concentration (9.91%), stomatal conductance (15.49%), photosynthetic rate (25.50%), and transpiration rate (10.46%) were observed, validating the efficacy of 1.20% deashed biochar in alleviating salinity stress. The study also demonstrated a significant decrease in the activities of oxidative stress markers such as peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), electrolyte leakage, and malondialdehyde (MDA). Simultaneously, there was an increase in the concentrations of essential nutrients, namely nitrogen (N), phosphorus (P), and potassium (K), in both shoot and root tissues. These findings collectively suggest that deashed biochar, particularly at a concentration of 1.20%, is recommended for achieving enhanced crop production under conditions of salinity stress.

Abstract Alzheimer's disease (AD) is considered the leading cause of dementia in the elderly worldwide. It results in progressive memory loss and impairment of cognitive and motor skills, leading to a high degree of disability and dependence. The development of AD is associated with the accumulation of senile plaques in the brain, caused by the amyloidogenic pathway of the disease. Several genetic and biochemical events are linked to AD development, with oxidative stress being one of them. Due to the scarcity of drugs aimed at treating AD, antioxidant compounds are increasingly studied as therapeutic targets for the disease. In this study, we investigate the antioxidant and anti-Alzheimer potential of the Tetragonisca angustula (Jataí) pollen extract in a Drosophila melanogaster Alzheimer's model. For this purpose, we utilized a D. melanogaster AD-like model, which expresses genes related to the amyloidogenic pathway of Alzheimer's disease. We explored the floral origin of the collected pollen, conducted phytochemical prospecting, and evaluated its antioxidant capacity in vitro. In vivo experiments involved assessing the survival and climbing ability of the D. melanogaster AD-like model with various concentrations of the pollen extract. Our findings revealed that the pollen extract of Tetragonisca angustula exhibits a significant antioxidant response and high concentrations of important phytochemicals, such as flavonoids and polyphenols. Furthermore, it enhanced the survival rate of D. melanogaster, and across all concentrations tested, it improved the climbing ability of the flies after 15 days of treatment with methanolic pollen extract. Additionally, the pollen extract reduced the neurodegeneration index in histopathological analysis. Thus, our study demonstrates the potential of Tetragonisca angustula pollen as an important subject for further investigation, aiming to isolate molecules that could potentially serve as therapeutic targets for Alzheimer's disease.

Abstract Drought and cadmium (Cd) stress are both major issues that significantly affect the growth and development of wheat plants. Both drought stress and Cd toxicity disrupt physiological processes i.e., nutrient uptake, cell expansion, and enzymatic reactions resulting in poor crop growth. To overcome these issues, the use of activated carbon and gibberellic acid (GA3) are considered valuable amendments. However, the current study aimed to add value using GA3-enriched biochar (GA3-BC). That’s why, a lab experiment was conducted on wheat to assess the effectiveness of GA3-BC against Cd and drought stress. For GA3 enrichment in biochar, 10 µg GA3/g biochar was mixed. There were 3 levels of GA3-BC i.e., 0, 0.6 (GA3-BC1), and 0.9% (GA3-BC). All levels were applied in 3 replicates under no stress (0Cd + no drought), drought stress (DS), and 6 mg Cd/ kg soil (6Cd). Results showed that GA3-BC2 caused a significant improvement in shoot length (44.99%), root length (99.73%), seedling length (60.13%) and shoot fresh weight (63.59%) over control at 6Cd + drought stress. A significant improvement in chlorophyll a, chlorophyll b, and total chlorophyll while a decrease in electrolyte leakage and regulation of antioxidants i.e., lipid peroxidation, SOD, CAT, APx, GR, GPx, GST, and DPHH also signified the effectiveness of GA3-BC2 compared to control at 6Cd + drought stress. In conclusion, GA3-BC2 is an efficacious amendment for simultaneously alleviating drought and Cd stress in wheat. More investigations are recommended at the field level on different cereal crops cultivated in different soil textures to declare GA3-BC2 as the best treatment for mitigation of drought stress and Cd toxicity.

Abstract The aim of our study was to investigate whether self-reported feeling of loneliness (FoL) and COVID-19-specific health anxiety were associated with the presence of depressive symptoms during the first coronavirus disease 2019 (COVID-19) wave. Questionnaires of 603 persons of the Swiss Multiple Sclerosis Registry (SMSR) were cross-sectionally analyzed using descriptive and multivariable regression methods. The survey response rate was 63.9%. Depressive symptoms were assessed by the Beck Depression Inventory-Fast Screen (BDI-FS). COVID-19-specific health anxiety and FoL were measured using two 5-item Likert scaled pertinent questions. High scoring FoL (2.52, 95% confidence interval (CI) (2.06—2.98)) and/or COVID-19 specific health anxiety (1.36, 95% CI (0.87–1.85)) were significantly associated with depressive symptoms. Further stratification analysis showed that the impact of FoL on depressive symptoms affected all age groups. However, it was more pronounced in younger PwMS, whereas an impact of COVID-19 specific health anxiety on depressive symptoms was particularly observed in middle-aged PwMS. FoL and COVID-19-specific health anxiety were age-dependently associated with depressive symptoms during the first COVID-19 wave in Switzerland. Our findings could guide physicians, health authorities, and self-help groups to better accompany PwMS in times of public health crises.

Abstract Alzheimer’s disease (AD) is the most common form of dementia in the elderly, affecting cognitive, intellectual, and motor functions. Different hypotheses explain AD’s mechanism, such as the amyloidogenic hypothesis. Moreover, this disease is multifactorial, and several studies have shown that gut dysbiosis and oxidative stress influence its pathogenesis. Knowing that kefir is a probiotic used in therapies to restore dysbiosis and that the bioactive peptides present in it have antioxidant properties, we explored its biotechnological potential as a source of molecules capable of modulating the amyloidogenic pathway and reducing oxidative stress, contributing to the treatment of AD. For that, we used Drosophila melanogaster model for AD (AD-like flies). Identification of bioactive peptides in the kefir sample was made by proteomic and peptidomic analyses, followed by in vitro evaluation of antioxidant and acetylcholinesterase inhibition potential. Flies were treated and their motor performance, brain morphology, and oxidative stress evaluated. Finally, we performed molecular docking between the peptides found and the main pathology-related proteins in the flies. The results showed that the fraction with the higher peptide concentration was positive for the parameters evaluated. In conclusion, these results revealed these kefir peptide-rich fractions have therapeutic potential for AD.

Abstract Alzheimer’s Disease (AD) is the most common cause of dementia among elderly individuals worldwide, leading to a strong motor-cognitive decline and consequent emotional distress and codependence. It is traditionally characterized by amyloidogenic pathway formation of senile plaques, and recent studies indicate that dysbiosis is also an important factor in AD’s pathology. To overcome dysbiosis, probiotics—as kefir—have shown to be a great therapeutic alternative for Alzheimer’s disease. In this present work, we explored kefir as a probiotic and a metabolite source as a modulator of microbiome and amyloidogenic pathway, using a Drosophila melanogaster model for AD (AD-like flies). Kefir microbiota composition was determined through 16S rRNA sequencing, and the metabolome of each fraction (hexane, dichloromethane, ethyl acetate, and n-butanol) was investigated. After treatment, flies had their survival, climbing ability, and vacuolar lesions accessed. Kefir and fraction treated flies improved their climbing ability survival rate and neurodegeneration index. In conclusion, we show that kefir in natura, as well as its fractions may be promising therapeutic source against AD, modulating amyloidogenic related pathways.

Abstract Segmentation of white matter lesions and deep grey matter structures is an important task in the quantification of magnetic resonance imaging in multiple sclerosis. In this paper we explore segmentation solutions based on convolutional neural networks (CNNs) for providing fast, reliable segmentations of lesions and grey-matter structures in multi-modal MR imaging, and the performance of these methods when applied to out-of-centre data. We trained two state-of-the-art fully convolutional CNN architectures on the 2016 MSSEG training dataset, which was annotated by seven independent human raters: a reference implementation of a 3D Unet, and a more recently proposed 3D-to-2D architecture (DeepSCAN). We then retrained those methods on a larger dataset from a single centre, with and without labels for other brain structures. We quantified changes in performance owing to dataset shift, and changes in performance by adding the additional brain-structure labels. We also compared performance with freely available reference methods. Both fully-convolutional CNN methods substantially outperform other approaches in the literature when trained and evaluated in cross-validation on the MSSEG dataset, showing agreement with human raters in the range of human inter-rater variability. Both architectures showed drops in performance when trained on single-centre data and tested on the MSSEG dataset. When trained with the addition of weak anatomical labels derived from Freesurfer, the performance of the 3D Unet degraded, while the performance of the DeepSCAN net improved. Overall, the DeepSCAN network predicting both lesion and anatomical labels was the best-performing network examined.