Development of Patient and Caregiver Conceptual Models Investigating the Health-Related Quality of Life Impacts of Malignant Pleural Mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and usually fatal malignancy frequently linked to occupational asbestos exposures and associated with poor prognosis and considerable humanistic burden. The study aimed to develop conceptual models of the health-related quality of life (HRQoL) impact on patients with and receiving treatment for MPM, and the burden on their caregivers. METHODS: This multi-country study (Australia and United Kingdom) adopted a qualitative methodology to conduct semi-structured, independent interviews with people with MPM (n = 26), current caregivers (n = 20), and caregivers of people who had recently died because of MPM (n = 4). Participants were recruited using a purposive sampling approach and interviews conducted via telephone between January 2021 and January 2022. Transcripts were analysed using thematic analysis and used to construct conceptual models. RESULTS: Patient analysis yielded four overarching themes: (1) debilitating burden of breathlessness and fatigue; (2) physical mesothelioma symptoms experienced by patients; (3) distress of MPM on the self and family; and (4) treatment is worth 'having a go' despite the potential impact on symptoms. Caregiver analysis yielded five core themes: (1) daily life limited by caregiving duties; (2) emotional well-being and the need for support; (3) the relational role shift to caregiver; (4) time spent providing care negatively impacts work and productivity; and (5) positive aspects and outcomes of caregiving. CONCLUSIONS: This study highlights the substantial daily and emotional HRQoL impact that MPM symptoms have on patients and caregivers. Both groups reduced work, productivity, and social and leisure activities. There was evidence of positive HRQoL impacts as a result of immunotherapy and radiotherapy, but less for chemotherapy. Caregiver impacts were intensified during the end-of-life period and persisted following patient death. Evident is a need for increased psychological support, information, and advice for caregivers, increased during the end-of-life period.

A novel output feedback consensus control approach for generic linear multi-agent systems under input saturation over a directed graph topology.

This paper considers an output feedback consensus control approach for the generic linear multi-agent systems (MASs) under input saturation over a directed graph. A region of stability-based approach has been established for dealing with the input saturation. A conventional Luenberger observer for estimating the states of followers by themselves and an advanced cooperative observer for estimating the state of leader by followers have been applied for an estimated state feedback control. The stability conditions have been derived by considering a three-term-based combined Lyapunov function. Moreover, computationally simple controller and estimator design conditions have been obtained by resorting to a decoupling approach A set of initial conditions has been investigated to achieve the leader-following consensus of MASs under the input saturation constraint. To the best of our knowledge, an output feedback consensus approach, providing a consensus region, for generic linear MASs under input saturation over directed graphs without requiring the exact state of the leader has been explored for the first time. In contrast to the existing methods, the proposed approach considers an output feedback approach (rather than the state feedback), accounts for both linear and nonlinear saturation regions, applies an estimate of the state of the leader through cooperative observer, and is based on a generalized sector condition for the saturation nonlinearity. In addition, it offers a computationally simple design solution owing to the proposed decoupling method. Simulation results are provided to validate the efficacy of the designed protocol for F-18 aircraft and unmanned ground vehicles.

A time trade-off study to determine health-state utilities of transplant recipients with refractory cytomegalovirus infection with or without resistance.

BACKGROUND: Health-state utility values (HSUVs) for post-transplant refractory cytomegalovirus (CMV) infection (with or without resistance [R/R]) were determined using a time trade-off (TTO) survey completed by 1,020 members of the UK general public. METHODS: Existing literature and qualitative interviews with clinicians experienced in treating R/R CMV were used to develop initial draft vignettes of health states. The vignettes were refined to describe three clinical states of R/R CMV: clinically significant and symptomatic (CS-symptomatic CMV); clinically significant and asymptomatic (CS-asymptomatic CMV); and non-clinically significant (non-CS CMV). Each clinical state was valued independently and combined with three events of interest: graft-versus-host disease; kidney graft loss; and lung graft loss to generate twelve vignettes. The final vignettes were evaluated by a sample of the UK general public using an online TTO survey. Exclusion criteria were applied to the final data to ensure that responses included in the analysis met pre-defined quality control criteria. RESULTS: Overall, 738 participants met the inclusion criteria and were included in the analysis. The sample was representative of the UK general population in terms of age and sex. Non-CS CMV had the highest mean HSUV (95% confidence interval) (0.815 [0.791, 0.839]), followed by CS-asymptomatic CMV (0.635 [0.602, 0.669]), and CS-symptomatic CMV (0.443 [0.404, 0.482]). CS-symptomatic CMV with lung graft loss had the lowest mean HSUV (0.289), with none of the health states considered on average worse than dead. CONCLUSIONS: Post transplant R/R CMV has substantial impact on the health-related quality of life of patients. The utility values obtained in this study may be used to support economic evaluations of therapies for R/R CMV infection.

Biochar and nano biochar: Enhancing salt resilience in plants and soil while mitigating greenhouse gas emissions: A comprehensive review.

Salinity stress poses a significant challenge to agriculture, impacting soil health, plant growth and contributing to greenhouse gas (GHG) emissions. In response to these intertwined challenges, the use of biochar and its nanoscale counterpart, nano-biochar, has gained increasing attention. This comprehensive review explores the heterogeneous role of biochar and nano-biochar in enhancing salt resilience in plants and soil while concurrently mitigating GHG emissions. The review discusses the effects of these amendments on soil physicochemical properties, improved water and nutrient uptake, reduced oxidative damage, enhanced growth and the alternation of soil microbial communities, enhance soil fertility and resilience. Furthermore, it examines their impact on plant growth, ion homeostasis, osmotic adjustment and plant stress tolerance, promoting plant development under salinity stress conditions. Emphasis is placed on the potential of biochar and nano-biochar to influence soil microbial activities, leading to altered emissions of GHG emissions, particularly nitrous oxide(N2O) and methane(CH4), contributing to climate change mitigation. The comprehensive synthesis of current research findings in this review provides insights into the multifunctional applications of biochar and nano-biochar, highlighting their potential to address salinity stress in agriculture and their role in sustainable soil and environmental management. Moreover, it identifies areas for further investigation, aiming to enhance our understanding of the intricate interplay between biochar, nano-biochar, soil, plants, and greenhouse gas emissions.

Cost-utility analysis of ferric derisomaltose versus ferric carboxymaltose in patients with inflammatory bowel disease and iron deficiency anemia in England.

AIMS: Anemia is the most common extraintestinal complication of inflammatory bowel disease (IBD), with approximately half of cases caused by iron deficiency (ID). Intravenous iron is the preferred ID anemia (IDA) treatment where oral iron is contraindicated, ineffective or not tolerated, or where ID correction is urgent. The objective was to evaluate the cost-utility of ferric derisomaltose (FDI) versus ferric carboxymaltose (FCM) in patients with IBD and IDA in England, in whom IV iron treatment is preferred. MATERIALS AND METHODS: A patient-level simulation model was developed, capturing quality of life (QoL) differences based on SF-36v2 data from the PHOSPHARE-IBD randomized controlled trial, monitoring and incidence of post-infusion hypophosphatemia, and number of iron infusions required. Analyses were conducted over a five-year time horizon from the Department of Health and Social Care (DHSC) perspective, with healthcare provider and societal perspectives adopted in separate analyses. Future costs and effects were discounted at 3.5% per annum and one-way and probabilistic sensitivity analyses were performed. RESULTS: FDI increased quality-adjusted life expectancy by 0.075 QALYs versus FCM from 2.57 QALYs to 2.65 QALYs per patient. Patients receiving FDI required 1.63 fewer iron infusions over the five-year time horizon, driving infusion-related cost savings of GBP 496 per patient (GBP 2,188 versus GBP 1,692) from the DHSC perspective. Costs of monitoring and treating hypophosphatemia after FCM were GBP 226, yielding total savings of GBP 722 per patient (GBP 2,414 versus GBP 1,692) over the five-year time horizon. FDI also led to reduced costs versus FCM in the societal and provider analyses and was therefore the dominant intervention across all three perspectives. LIMITATIONS: The analysis did not capture patient adherence, hypophosphatemic osteomalacia, or fractures. CONCLUSIONS: Results showed that FDI improved patient QoL and reduced direct healthcare expenditure versus FCM in patients with IBD and IDA in England.

Ferric derisomaltose (FDI) is an intravenous iron approved for the treatment of clinically diagnosed iron deficiency in the United Kingdom (UK), and can be an important therapeutic option for patients with inflammatory bowel disease (IBD), who require regular and rapid iron replenishment. Ferric carboxymaltose (FCM) is the sole alternative intravenous iron formulation available in the UK, but is associated with reduced blood phosphate levels, potentially causing fatigue and weakening of the bones. We conducted an economic analysis to weigh the costs and clinical outcomes associated with FDI and FCM in the UK, for patients with IBD and iron deficiency anemia (IDA). The main clinical difference we investigated was reduced blood phosphate levels, which occurred more often after FCM than FDI. We also incorporated recent quality of life data from a clinical study, and calculated the number of infusions (and associated costs) of each iron formulation, that patients would require over five years. Clinical data were obtained from published medical literature, while cost data came from UK sources including the 2022/2023 National Tariff Payment System and the British National Formulary. Our model showed that FDI was associated with quality of life improvements, fewer overall infusions per treatment course, and reduced costs compared to FCM, from the English Department of Health and Social Care perspective, the societal perspective, and the perspective of individual healthcare providers (namely NHS Trusts) within NHS England. FDI is therefore likely to represent the best value intravenous iron for the treatment of IDA with IBD in the UK.

Physicochemical, Rheological and Sensory Evaluation of Herbal Bread Containing Turmeric, Ginger, and Black Cumin Powder.

The diversity in the global food market is expanding as thousands of new products enter the business every year, among which nutraceutical and functional foods hold important positions. The present research work aimed at the nutritional evaluation of three medicinal herbs, i.e., turmeric (Curcuma longa L.), ginger (Zingiber officinale), and black cumin (Nigella sativa). A bread formulation was enriched with the individual/combined supplementation (1-3%) of these herbs. Later, the bread was analyzed for nutritional, rheological, textural, and sensorial characteristics. The results revealed that the herbs improved the nutritional composition of bread, especially ash and fiber, as the maximum ash and fiber contents were noticed in T15 (2.0% dried powder of each plant) with values of 1.64 ± 0.04% and 4.63 ± 0.16%, respectively. The results regarding the rheological behavior showed minor variations in the rheological traits and a slight increase in dough development time up to 4.50 ± 0.20 min in T10 from 2.80 ± 0.13 min in T0. The sensorial attributes also indicated their marked suitability as external and internal characteristics were least affected by the addition of the herbs. Although some parameters like the crust and crumb colors were affected by the addition of black cumin, showing values of 6.25 ± 0.52 and 4.44 ± 0.19, respectively, in T15, and aroma characteristics were affected by the addition of ginger, supplementation with a combination of herbs at lower doses mitigated the adverse effects of other herbs. Moreover, shelf-life extension, especially with the addition of turmeric powder, was the hallmark of this research. This study concluded that medicinal herbs can be incorporated into baked products to improve the nutritional and sensorial attributes of functional herbal bread.

The Health Economics of Automated Insulin Delivery Systems and the Potential Use of Time in Range in Diabetes Modeling: A Narrative Review.

Intensive therapy with exogenous insulin is the treatment of choice for individuals living with type 1 diabetes (T1D) and some with type 2 diabetes, alongside regular glucose monitoring. The development of systems allowing (semi-)automated insulin delivery (AID), by connecting glucose sensors with insulin pumps and algorithms, has revolutionized insulin therapy. Indeed, AID systems have demonstrated a proven impact on overall glucose control, as indicated by effects on glycated hemoglobin (HbA1c), risk of severe hypoglycemia, and quality of life measures. An alternative endpoint for glucose control that has arisen from the use of sensor-based continuous glucose monitoring is the time in range (TIR) measure, which offers an indication of overall glucose control, while adding information on the quality of control with regard to blood glucose level stability. A review of literature on the health-economic value of AID systems was conducted, with a focus placed on the growing place of TIR as an endpoint in studies involving AID systems. Results showed that the majority of economic evaluations of AID systems focused on individuals with T1D and found AID systems to be cost-effective. Most studies incorporated HbA1c, rather than TIR, as a clinical endpoint to determine treatment effects on glucose control and subsequent quality-adjusted life year (QALY) gains. Likely reasons for the choice of HbA1c as the chosen endpoint is the use of this metric in most validated and established economic models, as well as the limited publicly available evidence on appropriate methodologies for TIR data incorporation within conventional economic evaluations. Future studies could include the novel TIR metric in health-economic evaluations as an additional measure of treatment effects and subsequent QALY gains, to facilitate a holistic representation of the impact of AID systems on glycemic control. This would provide decision makers with robust evidence to inform future recommendations for health care interventions.

Cost-utility of real-time continuous glucose monitoring versus self-monitoring of blood glucose in people with insulin-treated Type II diabetes in France.

Aim: Clinical trials and real-world data for Type II diabetes both show that glycated hemoglobin (HbA1c) levels and hypoglycemia occurrence can be reduced by real-time continuous glucose monitoring (rt-CGM) versus self-monitoring of blood glucose (SMBG). The present cost-utility study investigated the long-term health economic outcomes associated with using rt-CGM versus SMBG in people with insulin-treated Type II diabetes in France. Materials & methods: Effectiveness data were obtained from a real-world study, which showed rt-CGM reduced HbA1c by 0.56% (6.1 mmol/mol) versus sustained SMBG. Analyses were conducted using the IQVIA Core Diabetes Model. A French payer perspective was adopted over a lifetime horizon for a cohort aged 64.5 years with baseline HbA1c of 8.3% (67 mmol/mol). A willingness-to-pay threshold of €147,093 was used, and future costs and outcomes were discounted at 4% annually. Results: The analysis projected quality-adjusted life expectancy was 8.50 quality-adjusted life years (QALYs) for rt-CGM versus 8.03 QALYs for SMBG (difference: 0.47 QALYs), while total mean lifetime costs were €93,978 for rt-CGM versus €82,834 for SMBG (difference: €11,144). This yielded an incremental cost-utility ratio (ICUR) of €23,772 per QALY gained for rt-CGM versus SMBG. Results were particularly sensitive to changes in the treatment effect (i.e., change in HbA1c), annual price and quality of life benefit associated with rt-CGM, SMBG frequency, baseline patient age and complication costs. Conclusion: The use of rt-CGM is likely to be cost-effective versus SMBG for people with insulin-treated Type II diabetes in France.

Health-related quality of life in mild-to-moderate COVID-19 in the UK: a cross-sectional study from pre- to post-infection.

BACKGROUND: The aim of this study was to estimate the impact of mild-to-moderate COVID-19 on health-related quality of life (HRQoL) over time among individuals in the United Kingdom, adding to the evidence base that had focussed on severe COVID-19. METHODS: A bespoke online survey was administered to individuals who self-reported a positive COVID-19 test. An amended version of a validated generic HRQoL instrument (EQ-5D-5L) was used to measure HRQoL retrospectively at different timepoints over the course of an infection: pre-COVID-19, acute COVID-19, and long COVID. In addition, HRQoL post-COVID-19 was captured by the original EQ-5D-5L questionnaire. A mixed-effects model was used to estimate changes in HRQoL over time, adjusted for a range of variables correlated with HRQoL. RESULTS: The study recruited 406 participants: (i) 300 adults and 53 adolescents with mild-to-moderate COVID-19 who had not been hospitalised for COVID-19 during acute COVID-19, and (ii) 53 adults who had been hospitalised for COVID-19 in the acute phase and who had been recruited for validation purposes. Data were collected between January and April 2022. Among participants included in the base-case analysis, EQ-5D-5L utility scores were lower during both acute COVID-19 (ß=-0.080, p = 0.001) and long COVID (ß=-0.072, p < 0.001) compared to pre COVID-19. In addition, EQ-5D-5L utility scores post-COVID-19 were found to be similar to the EQ-5D-5L utility scores before COVID-19, including for patients who had been hospitalised for COVID-19 during the acute phase or for those who had experienced long COVID. Moreover, being hospitalised in the acute phase was associated with additional utility decrements during both acute COVID-19 (ß=-0.147, p = 0.026) and long (ß=-0.186, p < 0.001) COVID. CONCLUSION: Patients perceived their HRQoL to have varied significantly over the course of a mild-to-moderate COVID-19 infection. However, HRQoL was found to return to pre-COVID-19 levels, even for patients who had been hospitalised for COVID-19 during the acute phase or for those who had experienced long COVID.

Engineered exosomes derived from stem cells: a new brain-targeted strategy.

INTRODUCTION: Using engineered exosomes produced from stem cells is an experimental therapeutic approach for treating brain diseases. According to reports, preclinical research has demonstrated notable neurogenesis and angiogenesis effects using modified stem cell-derived exosomes. These biological nanoparticles have a variety of anti-apoptotic, anti-inflammatory, and antioxidant properties that make them very promising for treating nervous system disorders. AREAS COVERED: This review examines different ways to enhance the delivery of modified stem cell-derived exosomes, how they infiltrate the blood-brain barrier (BBB), and how they facilitate their access to the brain. We would also like to determine whether these nanoparticles have the most significant transmission rates through BBB when targeting brain lesions. EXPERT OPINION: Using engineered stem cell-derived exosomes for treating brain disorders has generated considerable attention toward clinical research and application. However, stem cell-derived exosomes lack consistency, and their mechanisms of action are uncertain. Therefore, upcoming research needs to prioritize examining the underlying mechanisms and strategies via which these nanoparticles combat neurological disorders.

Leveraging COVID-19 Vaccine Safety Monitoring in Ethiopia and Pakistan to Enhance System-Wide Safety Surveillance.

The rapid development, introduction, and global uptake of COVID-19 vaccines required countries to have strong pharmacovigilance systems in place to monitor and address adverse events following immunization (AEFIs). These systems provide timely data on vaccine safety that support decisions about the potential risks of vaccine adverse events relative to the benefit of disease prevention. In Ethiopia, the monitoring system was limited by the lack of data being submitted through its passive surveillance system, delays in investigating serious adverse events and conducting causality assessments, and the lack of reporting to the World Health Organization (WHO) global database, VigiBase. In Pakistan, the pharmacovigilance system lacked reporting requirements and guidance documentation, regulatory policies were insufficient, and staff lacked the capacity to evaluate AEFI reports. Several interventions were implemented in both countries to improve pharmacovigilance systems and processes necessary to collect, analyze, and report AEFIs from health care facilities to the national level and facilitate the use of global and national electronic reporting tools. In addition, Pakistan improved the regulatory policy environment and engaged vaccine manufacturers and private sector health facilities in AEFI reporting for the first time in the country. Outcomes include an increased number of COVID-19 vaccine-related AEFIs reported and causality assessments completed, which means that potential safety issues were being analyzed more quickly, comprehensively, and accurately. The number of AEFI reports submitted to VigiBase by Pakistan's regulatory authority more than quintupled from approximately 5,000/quarter in 2021 to 28,555/quarter in 2022. In Ethiopia, by October 2022, 44,000 AEFI reports had been received, and 40 causality assessments completed. In both countries, timely AEFI data review and analysis led to prompt recommendations and regulatory actions, highlighting the far-reaching implications of strengthening the country-level pharmacovigilance systems. These strengthened systems are now in place for use with all vaccines.

Modelling the impact of sublingual immunotherapy versus subcutaneous immunotherapy on patient travel time and CO2 emissions in Sweden.

In Sweden, allergy immunotherapy (AIT) is available as either subcutaneous immunotherapy (SCIT) injections or sublingual immunotherapy (SLIT) tablets and is used to treat moderate-severe allergic rhinitis (AR). This study sought to determine treatment-related CO2 emissions and travel times in Swedish patients receiving either SCIT or SLIT-tablets. A list of specialized Swedish AR clinics that administer AIT was determined, and respective co-ordinates retrieved. Swedish municipality population data were obtained from a national database. The mean distance from each Swedish municipality to the nearest AR clinic was calculated, adjusted using a detour index, and weighted by estimated patient population size. Transport modality data were obtained from a Swedish urban transport study and CO2 emissions were obtained from Government sources. The mean number of annual SLIT-tablets and SCIT doses required were calculated based on product labels and clinical expert input. The annual number of healthcare professional interactions were layered into the model to estimate changes in mean patient travel time, distance, and travel-related CO2 emissions associated with using SCIT versus SLIT-tablets. Mean annual travel-related CO2 emissions were 410 tonnes (to two significant figures [s.f.]; standard deviation [SD] 90) with SLIT-tablets, versus 1700 tonnes (SD 380) for SCIT, resulting in mean annual savings of approximately 1300 tonnes (SD 290) of CO2 if all AIT patients were to receive SLIT-tablets instead of SCIT, over 380 times greater than 2021 average Swedish CO2 emissions per capita. Approximate mean annual travel times for patients taking SLIT-tablets were 66,500 h (three s.f.; SD 14,400), and 278,000 h (SD 60,200) for SCIT, resulting in mean annual savings of 211,000 h (SD 45,800) if all AIT patients were to receive SLIT-tablets instead of SCIT. Compared with SCIT injections, SLIT-tablets led to substantial reductions in treatment-related CO2 emissions and travel times for Swedish patients.

A study on the effectiveness of sodium selenite in treating cadmium and perfluoro octane sulfonic (PFOS) poisoned zebrafish (Danio rerio).

Perfluoro octane sulfonate (PFOS) and cadmium (Cd) are toxic elements in the environment. As a micronutrient trace element, selenium (Se) can mitigate the adverse effects induced by PFOS and Cd. However, few studies have examined the correlation between Se, PFOS and Cd in fish. The present study focused on the antagonistic effects of Se on PFOS+Cd-induced accumulation in the liver of zebrafish. The fish was exposed to PFOS (0.08mg/L), Cd (1mg/L), PFOS+ Cd (0.08 mg/L PFOS+1 mg/L Cd), L-Se (0.07mg/L Sodium selenite +0.08mg/L PFOS+1mg/L Cd), M-Se (0.35mg/L Sodium selenite + 0.08mg/L PFOS+ 1 mg/L Cd), H-Se (1.75 mg/L Sodium selenite + 0.08 mg/L PFOS+ 1mg/L Cd) for 14d. The addition of selenium to fish exposed to PFOS and Cd has been found to have significant positive effects. Specifically, selenium treatments can alleviate the adverse effects of PFOS and Cd on fish growth, with a 23.10% improvement observed with the addition of T6 compared to T4. In addition, selenium can alleviate the negative effects of PFOS and Cd on antioxidant enzymes in zebrafish liver, thus reducing the liver toxicity caused by PFOS and Cd. Overall, the supplementation of selenium can reduce the health risks to fish and mitigate the injuries caused by PFOS and Cd in zebrafish.

Review on microgrids design and monitoring approaches for sustainable green energy networks.

Microgrids are power distribution systems that can operate either in a grid-connected configuration or in an islanded manner, depending on the availability of decentralized power resources, such as sustainable or non-sustainable power sources, battery backup systems, and power demands. The extensive adoption of inverter-based systems poses numerous technological challenges, necessitating a centralized management system to assure the system reliability and monitoring of the energy delivery networks. Thus, this research begins by highlighting these significant obstacles and then analyzes the present-day advances in multilevel control architecture for delivering on promised functionality. This article also discusses the development of innovative control technologies, such as introducing collaborative distributed approaches and reducing conventional three-stage patriarchal administration to fewer stages of system integration and functioning.

Comparison of Efficacy of Fermented Garlic and Orlistat (Lipase Inhibitor) in Obesity Management Using an Experimental Rodent Model.

BACKGROUND: Black garlic, also known as fermented garlic, is a useful food that may have therapeutic benefits. The aim of this study was to analyze the impact of fermented garlic and orlistat therapy on obese rats. METHODS: A total of 40 male albino rats (245-250 g) were fed either an HFD (n = 32) or a normal diet (n = 8) for 6 weeks; therefore we randomly assigned the rats into: group I (normal diet), group II (HFD), groups III and IV (HFD with fermented garlic), and group V (orlistat for) 6 weeks. Two different dosages of fermented garlic (481.2 mg/kg and 963.3 mg/kg) were administered. Afterward, blood was collected, body weight was measured, and tissue was collected for further analysis. RESULTS: Both the orlistat and black garlic groups showed a significant reduction in BMI, lipid profiles, and insulin levels compared with the baseline. The orlistat group showed significant elevation (p < 0.005) in body weight, organ weight, lipids, and liver parameters, with histopathological findings. The administration of black garlic improved the inflammatory markers with all other parameters. CONCLUSION: The fermented garlic and orlistat reinstated all of the investigated parameters significantly (p < 0.05), especially body weight and lipid profiles, and induced histopathological changes compared to the drug orlistat. Additionally, it showed anti-obesity-related therapeutic impacts compared with the orlistat drug. Black garlic provides a reliable and effective treatment for obesity compared to orlistat.

ZnO nanoparticles mediated by Azadirachta indica as nano fertilizer: Improvement in physiological and biochemical indices of Zea mays grown in Cr-contaminated soil.

The current investigation aimed at evaluating the impact of Azadirachta indica-mediated zinc oxide nanoparticles (Ai-ZnONPs) on the growth and biochemical characteristics of maize (sweet glutinous 3000) under exposure to 50 mg kg-1Ai-ZnONPs with Cr (VI) concentrations of 50 and 100 mg kg-1. The results indicate that plants exposed to Cr (VI) only experienced a decline in growth parameters. Conversely, the inclusion of Ai-ZnONPs caused a noteworthy increase in physiological traits. Specifically, shoot and root fresh weight increased by 28.02% and 16.51%, and 63.11% and 97.91%, respectively, when compared to Cr-50 and 100 treatments. Additionally, the SPAD chlorophyll of the shoot increased by 91.08% and 15.38% compared to Cr-50 and 100 treatments, respectively. Moreover, the antioxidant enzyme traits of plant shoot and root, such as superoxide dismutase (SOD 7.44% and 2.70%, and 4.45% and 3.53%), catalase (CAT 1.18% and 3.20%, and 5.03% and 5.78%), and peroxidase (POD 0.31% and 5.55%, and 4.72% and 3.61%), exhibited significant increases in Cr 50 and 100 treatments, respectively. The addition of Ai-ZnONPs to the soil also enhanced soil nutrient status and reduced Cr (VI) concentrations by 40.69% and 19.82% compared to Cr-50 and 100 treated soils. These findings suggest that Ai-ZnONPs can trigger the activation of biochemical pathways that enable biomass accumulation in meristematic cells. Further investigations are required to elucidate the mechanisms involved in growth promotion.

SARS-CoV-2 and Brain Health: New Challenges in the Era of the Pandemic.

Respiratory viral infections have been found to have a negative impact on neurological functions, potentially leading to significant neurological impairment. The SARS-CoV-2 virus has precipitated a worldwide pandemic, posing a substantial threat to human lives. Growing evidence suggests that SARS-CoV-2 may severely affect the CNS and respiratory system. The current prevalence of clinical neurological issues associated with SARS-CoV-2 has raised significant concerns. However, there needs to be a more comprehensive understanding of the specific pathways by which SARS-CoV-2 enters the nervous system. Based on the available evidence, this review focuses on the clinical neurological manifestations of SARS-CoV-2 and the possible mechanisms by which SARS-CoV-2 invades the brain.

Physiological and biochemical responses of soft coral Sarcophyton trocheliophorum to doxycycline hydrochloride exposure.

In light of the rapid expansion of the marine aquaculture industry, there has been widespread and irregular usage of aquatic drugs to combat biological diseases, which significantly impact the neighboring aquatic ecosystems. This study delves into the impact of the antibiotic aquatic drug known as doxycycline hydrochloride (DOX) on offshore soft corals, providing valuable data for the responsible use and management of aquatic drugs. In this investigation, we subjected Sarcophyton trocheliophorum to acute exposure to varying concentrations of DOX (0, 1, 5, and 10 mg L-1). We meticulously assessed critical parameters and observed alterations in protein levels, superoxide dismutase (SOD) activity, catalase (CAT) activity, lipid peroxidation (LPO), malondialdehyde (MDA) levels, Acid phosphatase (ACP) activity, alkaline phosphatase (AKP) activity, glutathione (GSH) concentration, glutathione S-transferase (GST) activity, glutathione Peroxidase (GSH-Px) activity, zooxanthellae density, and chlorophyll content. Our findings reveal that in the presence of DOX-induced environmental stress, there is a significant increase in LPO, MDA, chlorophyll, carotenoid levels, and the activities of ACP, GST, and GSH-Px in soft corals. Simultaneously, there is a noteworthy decrease in zooxanthellae density. Additionally, the protein concentration and SOD activity in soft corals experience substantial reduction when exposed to 5 mg L-1 DOX. Notably, CAT activity varies significantly in environments with 1 and 10 mg L-1 DOX. Moreover, these conditions exhibit a discernible influence on AKP activity, GSH content, and chlorophyll levels. These findings suggest that DOX exposure carries the potential for toxicity in aquaculture settings, affecting protein synthesis in soft corals and influencing oxidative stress, lipid peroxidation, immunity, and detoxification processes within these organisms. There is also a risk of compromising the coral defense system, potentially leading to coral bleaching. Furthermore, this study underscores the significant impact on photosynthesis, growth, and the metabolic dynamics of the coral-zooxanthellae symbiotic system. Consequently, our research offers vital insights into the mortality and bleaching effects of aquatic drugs on marine corals, offering a foundation for the prudent use and management of such substances.

Neural stem cell-derived exosomes-loaded adhesive hydrogel controlled-release promotes cerebral angiogenesis and neurological function in ischemic stroke.

OBJECTIVE: Ischemic stroke has become one of the leading diseases for international death, which brings burden to the economy and society. Exosomes (Exos) derived following neural stem cells (NSCs) stimulation promote neurogenesis and migration of NSCs. However, Exos themselves are easily to be removed in vivo. Our study is to investigate whether adhesive hyaluronic acid (HAD) hydrogel loading NSCs-derived-Exo (HAD-Exo) would promote the recovery of ischemic stroke. METHODS: A mouse model of middle cerebral artery occlusion (MCAO) was established. PBS, Exo, HAD, and HAD-Exo groups were independently stereotactically injected in mice, respectively. The modified neurological severity score scale and behaviour tests were used to evaluate neurological improvement. Neuroimagings were used to observe the improvement of cerebral infarct volume and vessels. Immunofluorescence staining was used to verify the expression of vascular and cell proliferation-related proteins. RESULTS: The structural and mechanical property of HAD and HAD-Exo were detected. Behavioral results showed that HAD-Exo significantly improved neurological functions, especially motor function. Neuroimagings showed that HAD-Exo significantly promoted infarct volume and angiogenesis. Immunofluorescence staining showed that HAD-Exo significantly promoted the cerebral angiogenesis and anti-inflammation. CONCLUSION: NSCs derived exosomes-loaded adhesive HAD hydrogel controlled-release could promote cerebral angiogenesis and neurological function for ischemic stroke.

Engineered Extracellular Vesicles for Drug Delivery in Therapy of Stroke.

Extracellular vesicles (EVs) are promising therapeutic modalities for treating neurological conditions. EVs facilitate intercellular communication among brain cells under normal and abnormal physiological conditions. The potential capability of EVs to pass through the blood-brain barrier (BBB) makes them highly promising as nanocarrier contenders for managing stroke. EVs possess several potential advantages compared to existing drug-delivery vehicles. These advantages include their capacity to surpass natural barriers, target specific cells, and stability within the circulatory system. This review explores the trafficking and cellular uptake of EVs and evaluates recent findings in the field of EVs research. Additionally, an overview is provided of the techniques researchers utilize to bioengineer EVs for stroke therapy, new results on EV-BBB interactions, and the limitations and prospects of clinically using EVs for brain therapies. The primary objective of this study is to provide a comprehensive analysis of the advantages and challenges related to engineered EVs drug delivery, specifically focusing on their application in the treatment of stroke.