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Abstract Background Treatment decisions for persons with relapsing–remitting multiple sclerosis (RRMS) rely on clinical and radiological disease activity, the benefit-harm profile of drug therapy, and preferences of patients and physicians. However, there is limited evidence to support evidence-based personalized decision-making on how to adapt disease-modifying therapy treatments targeting no evidence of disease activity, while achieving better patient-relevant outcomes, fewer adverse events, and improved care. Serum neurofilament light chain (sNfL) is a sensitive measure of disease activity that captures and prognosticates disease worsening in RRMS. sNfL might therefore be instrumental for a patient-tailored treatment adaptation. We aim to assess whether 6-monthly sNfL monitoring in addition to usual care improves patient-relevant outcomes compared to usual care alone. Methods Pragmatic multicenter, 1:1 randomized, platform trial embedded in the Swiss Multiple Sclerosis Cohort (SMSC). All patients with RRMS in the SMSC for ≥ 1 year are eligible. We plan to include 915 patients with RRMS, randomly allocated to two groups with different care strategies, one of them new (group A) and one of them usual care (group B). In group A, 6-monthly monitoring of sNfL will together with information on relapses, disability, and magnetic resonance imaging (MRI) inform personalized treatment decisions (e.g., escalation or de-escalation) supported by pre-specified algorithms. In group B, patients will receive usual care with their usual 6- or 12-monthly visits. Two primary outcomes will be used: (1) evidence of disease activity (EDA3: occurrence of relapses, disability worsening, or MRI activity) and (2) quality of life (MQoL-54) using 24-month follow-up. The new treatment strategy with sNfL will be considered superior to usual care if either more patients have no EDA3, or their health-related quality of life increases. Data collection will be embedded within the SMSC using established trial-level quality procedures. Discussion MultiSCRIPT aims to be a platform where research and care are optimally combined to generate evidence to inform personalized decision-making in usual care. This approach aims to foster better personalized treatment and care strategies, at low cost and with rapid translation to clinical practice. Trial registration ClinicalTrials.gov NCT06095271. Registered on October 23, 2023

Abstract Gene expression levels in rice (Oryza sativa L.) and other plant species are determined by the promoters, which directly control phenotypic characteristics. As essential components of genes, promoters regulate the intensity, location, and timing of gene expression. They contain numerous regulatory elements and serve as binding sites for proteins that modulate transcription, including transcription factors and RNA polymerases. Genome editing can alter promoter sequences, thereby precisely modifying the expression patterns of specific genes, and ultimately affecting the morphology, quality, and resistance of rice. This paper summarizes research on rice promoter editing conducted in recent years, focusing on improvements in yield, heading date, quality, and disease resistance. It is expected to inform the application of promoter editing and encourage further research and development in crop genetic improvement with promote.

Abstract Background Biochar, a carbon-rich source and natural growth stimulant, is usually produced by the pyrolysis of agricultural biomass. It is widely used to enhance plant growth, enzyme activity, and crop productivity. However, there are no conclusive studies on how different levels of biochar application influence these systems. Methods and results The present study elucidated the dose-dependent effects of biochar application on the physiological performance, enzyme activity, and dry matter accumulation of tobacco plants via field experiments. In addition, transcriptome analysis was performed on 60-day-old (early growth stage) and 100-day-old (late growth stage) tobacco leaves to determine the changes in transcript levels at the molecular level under various biochar application levels (0, 600, and 1800 kg/ha). The results demonstrated that optimum biochar application enhances plant growth, regulates enzymatic activity, and promotes biomass accumulation in tobacco plants, while higher biochar doses had adverse effects. Furthermore, transcriptome analysis revealed a total of 6561 differentially expressed genes (DEGs) that were up- or down-regulated in the groupwise comparison under different treatments. KEGG pathways analysis demonstrated that carbon fixation in photosynthetic organisms (ko00710), photosynthesis (ko00195), and starch and sucrose metabolism (ko00500) pathways were significantly up-regulated under the optimal biochar dosage (600 kg/ha) and down-regulated under the higher biochar dosage (1800 kg/ha). Conclusion Collectively, these results indicate that biochar application at an optimal rate (600 kg/ha) could positively affect photosynthesis and carbon fixation, which in turn increased the synthesis and accumulation of sucrose and starch, thus promoting the growth and dry matter accumulation of tobacco plants. However, a higher biochar dosage (1800 kg/ha) disturbs the crucial source-sink balance of organic compounds and inhibits the growth of tobacco plants.

Abstract Arsenic (As) contamination is a major environmental pollutant that adversely affects plant physiological processes and can hinder nutrients and water availability. Such conditions ultimately resulted in stunted growth, low yield, and poor plant health. Using rhizobacteria and composted biochar (ECB) can effectively overcome this problem. Rhizobacteria have the potential to enhance plant growth by promoting nutrient uptake, producing growth hormones, and suppressing diseases. Composted biochar can enhance plant growth by improving aeration, water retention, and nutrient cycling. Its porous structure supports beneficial microorganisms, increasing nutrient uptake and resilience to stressors, ultimately boosting yields while sequestering carbon. Therefore, the current study was conducted to investigate the combined effect of previously isolated Bacillus faecalis (B. faecalis) and ECB as amendments on maize cultivated under different As levels (0, 300, 600 mg As/kg soil). Four treatments (control, 0.5% composted biochar (0.5ECB), B. faecalis, and 0.5ECB + B. faecalis) were applied in four replications following a completely randomized design. Results showed that the 0.5ECB + B. faecalis treatment led to a significant rise in maize plant height (~ 99%), shoot length (~ 55%), root length (~ 82%), shoot fresh (~ 87%), and shoot dry weight (~ 96%), root fresh (~ 97%), and dry weight (~ 91%) over the control under 600As stress. There was a notable increase in maize chlorophyll a (~ 99%), chlorophyll b (~ 81%), total chlorophyll (~ 94%), and shoot N, P, and K concentration compared to control under As stress, also showing the potential of 0.5ECB + B. faecalis treatment. Consequently, the findings suggest that applying 0.5ECB + B. faecalis is a strategy for alleviating As stress in maize plants.

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.

Lignite and sulphur are instrumental in enhancing the growth and yield-related traits of Brassica napus, commonly known as rapeseed. This study aimed to explore the effects of lignite-based sulphur fertilizers on Brassica napus production. Spanning two consecutive seasons, the experiment included treatments with a control group, three levels of elemental sulphur (30, 40, and 50 kg ha-1), and three levels of lignite-based sulphur fertilizer (30, 40, and 50 kg ha-1). Employing a randomized complete block design with four replications, the study revealed that applying lignite-based sulphur fertilizer at a rate of 50 kg ha-1 led to significant improvements in various growth parameters, such as plant height, primary and secondary branches per plant, pods per plant, pod length, seeds per pod, biological yield, seed yield, thousand seed weight, and oil yield. Notably, substantially higher seed and oil yields were achieved with the application of 50 kg ha-1 of lignite-based sulphur fertilizer. In semi-arid climates, to maximize rapeseed yield, yield components, and quality, it is advisable to utilize lignite-based sulphur fertilizer at a rate of 50 kg ha-1.

Abstract This study explores the green synthesis of silver nanoparticles (AgNPs) using a methanolic extract of fermented pollen from Tetragonisca angustula, a species of stingless bees. The AgNPs exhibit spherical morphology, low charge values, and suspension stability, with their unique composition attributed to elements from the pollen extract. Antioxidant assays show comparable activity between the pollen extract and AgNPs, emphasizing the retention of antioxidant effects. The synthesized AgNPs demonstrate antimicrobial activity against multidrug-resistant bacteria, highlighting their potential in combating bacterial resistance. The AgNPs exhibit no toxic effects on Drosophila melanogaster and even enhance the hatching rate of eggs. The study underscores the innovative use of stingless bee pollen extract in green synthesis, offering insights into the varied applications of AgNPs in biomedicine.

Introduction. The prevalence of diabetes mellitus is increasing, with type 2 diabetes (T2DM) being a major health priority for any public health system. Increased arterial stiffness in patients with diabetes will lead to the appearance of vascular complications. Increased arterial stiffness in patients with diabetes usually leads to vascular complications. Any earlier diagnosis of impaired macrovascular evidence may lead to improved outcomes in patient care. The objective of our study was to assess and evaluate the finger-toe pulse wave velocity (ftPWV), as a measure of arterial stiffness, in order to assist with early detection of macrovascular diabetic complications. Materials and Methods. The observational case series included 140 patients who are registered in a primary care office, of whom 73 were previously diagnosed with diabetes mellitus (study group). The age-matched non-diabetic group included 67 consecutive registered patients who visited the practice for other reasons. Results. The mean age of all patients was 51.42±11.57 years, with DM patients being with 4.5 years older than the non-DM patients (CI 95% and CI 95%). There was a significantly higher mean value of ftPWV in the DM group (p = 0.0039) although the study presented some limitations. Conclusions. The mean value of ftPWV was statistically significant higher in diabetic patients. The assessment of ftPWV is a non-invasive test, and the data can be used as a useful marker of vascular stiffness in primary care, thus providing an early diagnosis of macrovascular complications during the monitoring and care of the diabetic patient.

Background: Hypothyroidism reduces circulating levels of thyroid hormones metabolic enzymatic activities, and the skeletal muscle's work capacity and lactatemia increase during exertion. Objectives: To analyze salivary biomarkers and blood lactate obtained in exercise stages through exhaustion and investigate their correlation. Methods: Eight females attended the University Clinical Hospital who showed a condition of subclinical hypothyroidism. Before they began replacing with L-thyroxine, they were submitted to an ergometric test to check their tolerance to effort. Eight weeks after treatment, all volunteers were again submitted to lab and ergometric tests. Saliva and blood were collected to determine total protein, nitric oxide, IgA, lactate, and lipid profile. Results: The present study identified a correlation (0.8), so the behavior of the blood lactate could explain the behavior of the salivary of total proteins by 74.22% (R2 = 0.7422). Lactate production was minimized when women underwent L-thyroxine treatment in the first six stages of exercise. Still, total salivary proteins increased for pharmacotherapy between stages 1 and 8. While salivary nitric oxide had a percentage variation between pre- and post-exercise times of 96% before the start of treatment when the same exercise was performed after eight weeks of treatment with L-Thyroxine, this variation was 150%. Conclusion: The measurement of STP is an essential marker of stress, and it is highly correlated with the most used blood marker, lactate. Regarding treatment with L-Thyroxine in women with subclinical hypothyroidism, after eight weeks of this therapy, it was possible to observe a reduction in blood lactate production after the incremental load test on a cycle ergometer, accompanied by a reduction in the concentration of SA. SNO and SIgA tended to increase in women undergoing treatment, and this treatment should be considered in subsequent studies as causing a different effect on these markers.

This study primarily investigates the antibacterial properties, tensile strength, flexural strength, impact strength, hardness, and microstructural characteristics of a composite, utilizing Scanning Electron Microscopy (SEM) for detailed analysis. The composite, crafted through a hand layup technique, optimally blends ramie and hemp fibers within an epoxy matrix. Its antibacterial efficacy was rigorously tested against common bacterial strains, demonstrating significant potential for medical and hygienic applications. The evaluation of tensile strength revealed the composite’s enhanced capability to withstand longitudinal stresses, with a peak strength of 37.81 MPa, achieved by increasing ramie fiber content. In addition, a flexural strength of 39.72 MPa underscored the material’s robust resistance to bending forces, crucial for structural uses. The composite’s impact strength, accessed via the Izod impact test, registered at 0.021 J/m2, indicating its ability to absorb and dissipate energy upon sudden impacts, making it ideal for automotive and protective gear applications. The Rockwell hardness test further quantified the composite’s resistance to surface indentation, vital for wear-resistant surfaces. SEM analysis offered a comprehensive view of the microstructural dynamics between the fibers and the matrix, especially under tensile stress, highlighting the intricacies of fiber–matrix adhesion, crack propagation, and overall composite integrity. Notably, the antibacterial properties were confirmed by an 18 mm inhibition zone, which showcases the composite’s ability to inhibit bacterial growth effectively.

The increasing pressures of urban development and agricultural expansion have significant implications for land use and land cover (LULC) dynamics, particularly in ecologically sensitive regions like the Murree and Kotli Sattian tehsils of the Rawalpindi district in Pakistan. This study's primary objective is to assess spatial variations within each LULC category over three decades (1992–2023) using cross-tabulation in ArcGIS to identify changes in LULC and investigates into forest fragmentation analysis using the Landscape Fragmentation Tool (LFTv2.0) to classify forest into several classes such as patch, edge, perforated, small core, medium core, and large core. Utilizing remote sensing data from Landsat 5 and Landsat 9 satellites, the research focuses on the temporal dynamics in various land classes including Coniferous Forest (CF), Evergreen Forest (EF), Arable Land (AR), Buildup Area (BU), Barren Land (BA), Water (WA), and Grassland (GL). The Support Vector Machine (SVM) classifier and ArcGIS software were employed for image processing and classification, ensuring accuracy in categorizing different land types. Our results indicate a notable reduction in forested areas, with Coniferous Forest (CF) decreasing from 363.9 km2, constituting 45.0 % of the area in 1992, to 291.5 km2 (36.0 %) in 2023, representing a total decrease of 72.4 km2. Similarly, Evergreen Forests have also seen a significant reduction, from 177.9 km2 (22.0 %) in 1992 to 99.8 km2 (12.3 %) in 2023, a decrease of 78.1 km2. The study investigates into forest fragmentation analysis using the Landscape Fragmentation Tool (LFTv2.0), revealing an increase in fragmentation and a decrease in large core forests from 20.3 % of the total area in 1992 to 7.2 % in 2023. Additionally, the patch forest area increased from 2.4 % in 1992 to 5.9 % in 2023, indicating significant fragmentation. Transition matrices and a Sankey diagram illustrate the transitions between different LULC classes, providing a comprehensive view of the dynamics of land-use changes and their implications for ecosystem services. These findings highlight the critical need for robust conservation strategies and effective land management practices. The study contributes to the understanding of LULC dynamics and forest fragmentation in the Himalayan region of Pakistan, offering insights essential for future land management and policymaking in the face of rapid environmental changes.

Abstract Salinity stress can significantly delay plant growth. It can disrupt water and nutrient uptake, reducing crop yields and poor plant health. The use of strigolactone can be an effective technique to overcome this issue. Strigolactone enhances plant growth by promoting root development and improvement in physiological attributes. The current pot study used strigolactone to amend chili under no salinity and salinity stress environments. There were four treatments, i.e., 0, 10µM strigolactone, 20µM strigolactone and 30µM strigolactone. All treatments were applied in four replications following a completely randomized design (CRD). Results showed that 20µM strigolactone caused a significant increase in chili plant height (21.07%), dry weight (33.60%), fruit length (19.24%), fruit girth (35.37%), and fruit yield (60.74%) compared to control under salinity stress. Significant enhancement in chili chlorophyll a (18.65%), chlorophyll b (43.52%), and total chlorophyll (25.09%) under salinity stress validated the effectiveness of 20µM strigolactone application as treatment over control. Furthermore, improvement in nitrogen, phosphorus, and potassium concentration in leaves confirmed the efficient functioning of 20µM strigolactone compared to other concentrations under salinity stress. The study concluded that 20µM strigolactone is recommended for mitigating salinity stress in chili plants. Growers are advised to apply 20µM strigolactone to enhance their chili production under salinity stress.

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 The deleterious impact of osmotic stress, induced by water deficit in arid and semi-arid regions, poses a formidable challenge to cotton production. To protect cotton farming in dry areas, it’s crucial to create strong plans to increase soil water and reduce stress on plants. The carboxymethyl cellulose (CMC), gibberellic acid (GA3) and biochar (BC) are individually found effective in mitigating osmotic stress. However, combine effect of CMC and GA3 with biochar on drought mitigation is still not studied in depth. The present study was carried out using a combination of GA3 and CMC with BC as amendments on cotton plants subjected to osmotic stress levels of 70 (70 OS) and 40 (40 OS). There were five treatment groups, namely: control (0% CMC-BC and 0% GA3-BC), 0.4%CMC-BC, 0.4%GA3-BC, 0.8%CMC-BC, and 0.8%GA3-BC. Each treatment was replicated five times with a completely randomized design (CRD). The results revealed that 0.8 GA3-BC led to increase in cotton shoot fresh weight (99.95%), shoot dry weight (95.70%), root fresh weight (73.13%), and root dry weight (95.74%) compared to the control group under osmotic stress. There was a significant enhancement in cotton chlorophyll a (23.77%), chlorophyll b (70.44%), and total chlorophyll (35.44%), the photosynthetic rate (90.77%), transpiration rate (174.44%), and internal CO2 concentration (57.99%) compared to the control group under the 40 OS stress. Thus 0.8GA3-BC can be potential amendment for reducing osmotic stress in cotton cultivation, enhancing agricultural resilience and productivity.

Abstract Drought stress poses a significant challenge to maize production, leading to substantial harm to crop growth and yield due to the induction of oxidative stress. Deashed biochar (DAB) in combination with carboxymethyl cellulose (CMC) presents an effective approach for addressing this problem. DAB improves soil structure by increasing porosity and water retention and enhancing plant nutrient utilization efficiency. The CMC provides advantages to plants by enhancing soil water retention, improving soil structure, and increasing moisture availability to the plant roots. The present study was conducted to investigate the effects of DAB and CMC amendments on maize under field capacity (70 FC) and drought stress. Six different treatments were implemented in this study, namely 0 DAB + 0CMC, 25 CMC, 0.5 DAB, 0.5 DAB + 25 CMC, 1 DAB, and 1 DAB + 25 CMC, each with six replications, and they were arranged according to a completely randomized design. Results showed that 1 DAB + 25 CMC caused significant enhancement in maize shoot fresh weight (24.53%), shoot dry weight (38.47%), shoot length (32.23%), root fresh weight (19.03%), root dry weight (87.50%) and root length (69.80%) over control under drought stress. A substantial increase in maize chlorophyll a (40.26%), chlorophyll b (26.92%), total chlorophyll (30.56%), photosynthetic rate (21.35%), transpiration rate (32.61%), and stomatal conductance (91.57%) under drought stress showed the efficiency of 1 DAB + 25 CMC treatment compared to the control. The enhancement in N, P, and K concentrations in both the root and shoot validated the effectiveness of the performance of the 1 DAB + 25 CMC treatment when compared to the control group under drought stress. In conclusion, it is recommended that the application of 1 DAB + 25 CMC serves as a beneficial amendment for alleviating drought stress in maize.

Abstract Heavy metal cadmium (Cd) naturally occurs in soil and is a hazardous trace contaminant for humans, animals, and plants. The main sources of Cd pollution in soil include overuse of phosphatic fertilizers, manure, sewage sludge, and aerial deposition. That’s why an experiment was conducted to analyze the effect of Cd toxicity in Capsicum annuum L. by selecting its seven varieties: Hybrid, Desi, Sathra, G-916, BR-763, BG-912, and F1-9226. Cadmium was spiked in soil with four levels, i.e., (0, 3, 4, and 5 mg Cd kg− 1 of soil) for a week for homogeneous dispersion of heavy metal. Chili seeds were sown in compost-filled loamy soil, and 25-day-old seedlings were transplanted into Cd-spiked soil. Cadmium increasing concentration in soil decreased chili growth characteristics, total soluble sugars, total proteins, and amino acids. On the other hand, the activities of antioxidant enzymes were increased with the increasing concentration of Cd in almost all the varieties. Treatment 5 mg Cd/kg application caused − 197.39%, -138.78%, -60.77%, -17.84%, -16.34%, -11.82% and − 10.37% decrease of carotenoids level in chili V2 (Desi) followed by V4 (G-916), V1 (Hy7brid), V7 (F1-9226), V6 (BG-912), V5 (BR-763) and V3 (Sathra) as compared to their controls. The maximum flavonoids among varieties were in V5 (BR-763), followed by V6 (BG-912), V7 (F1-9226), V3 (Sathra) and V1 (Hybrid). Flavonoids content was decreased with − 37.63% (Sathra), -34.78% (Hybrid), -33.85% (G-916), -31.96% (F1-9226), -31.44% (Desi), -30.58% (BR-763), -22.88% (BG-912) as compared to their control at 5 mg Cd/kg soil stress. The maximum decrease in POD, SOD, and CAT was − 31.81%, -25.98%, -16.39% in chili variety V7 (F1-9226) at 5 mg Cd/kg stress compared to its control. At the same time, maximum APX content decrease was − 82.91%, followed by -80.16%, -65.19%, -40.31%, -30.14%, -10.34% and − 6.45% in V4 (G-916), V2 (Desi), V3 (Sathra), V6 (BG-912), V1 (Hybrid), V7 (F1-9226) and V5 (BR-763) at 5 mg Cd/kg treatment as compared to control chili plants. The highest CAT was found in 5 chili varieties except Desi and G-916. Desi and G-916 varieties. V5 (BR-763) and V6 (BG-912) were susceptible, while V1 (Hybrid), V3 (Sathra), and V7 (F1-9226) were with intermediate growth attributes against Cd stress. Our results suggest that Desi and G-916 chili varieties are Cd tolerant and can be grown on a large scale to mitigate Cd stress naturally.