Integrated machine learning-based virtual screening and biological evaluation for identification of potential inhibitors against cathepsin K.

Cathepsin K is a type of cysteine proteinase that is primarily expressed in osteoclasts and has a key role in the breakdown of bone matrix protein during bone resorption. Many studies suggest that the deficiency of cathepsin K is concomitant with a suppression of osteoclast functioning, therefore rendering the resorptive properties of cathepsin K the most prominent target for osteoporosis. This innovative work has identified a novel anti-osteoporotic agent against Cathepsin K by using a comparison of machine learning and deep learning-based virtual screening followed by their biological evaluation. Out of ten shortlisted compounds, five of the compounds (JFD02945, JFD02944, RJC01981, KM08968 and SB01934) exhibit more than 50% inhibition of the Cathepsin K activity at 0.1 µM concentration and are considered to have a promising inhibitory effect against Cathepsin K. The comprehensive docking, MD simulation, and MM/PBSA investigations affirm the stable and effective interaction of these compounds with Cathepsin K to inhibit its function. Furthermore, the compounds RJC01981, KM08968 and SB01934 are represented to have promising anti-osteoporotic properties for the management of osteoporosis owing to their significantly well predicted ADMET properties.

Artificial intelligence and machine learning applications in the project lifecycle of the construction industry: A comprehensive review.

The construction industry faces many challenges, including schedule and cost overruns, productivity constraints, and workforce shortages. Compared to other sectors, it lags in digitalization in every project phase. Artificial Intelligence (AI) and Machine Learning (ML) have emerged as transformative technologies revolutionizing the construction sector. However, a discernible gap persists in systematically categorizing the applications of these technologies throughout the various phases of the construction project life cycle. In response to this gap, this research aims to present a thorough assessment of the deployment of AI and ML across diverse phases in construction projects, with the ultimate goal of furnishing valuable insights for the effective integration of these intelligent systems within the construction sector. A thorough literature review was performed to identify AI and ML applications in the building sector. After scrutinizing the literature, the applications of AI and ML were presented based on a construction project life cycle. A critical review of existing literature on AI and ML applications in the building industry showed that AI and ML applications are more frequent in the planning and construction stages. Moreover, the opportunities for AI and ML applications in other stages were discussed based on the life cycle categorization and presented in this study. The practical contribution of the study lies in providing valuable insights for the effective integration of intelligent systems within the construction sector. Academically, the research contributes by conducting a thorough literature review, categorizing AI and ML applications based on the construction project life cycle, and identifying opportunities for their deployment in different stages.

Prevalence and factors associated with depression and anxiety among COVID-19 survivors in Dhaka city.

Background: Coronavirus disease 2019 (COVID-19) is a global public health concern. Evidence shows that depression and anxiety are common among patients with COVID-19 after recovery. About one-third of the total COVID-19 cases in Bangladesh have been reported in Dhaka city. Therefore, the study aimed to evaluate the prevalence of depression and anxiety among COVID-19 survivors in Dhaka city as well as to identify the factors associated with these mental health conditions. Methods: A cross-sectional study was carried out among a total of 384 COVID-19 survivors aged 18 years or older. Data collection was done through face-to-face and telephone interviews using a semi-structured questionnaire. Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) scales were used to assess depression and anxiety, respectively. Binary logistic regression analysis was performed to identify the predictors of depression and anxiety among patients recovered from COVID-19. Results: The overall prevalence of depression and anxiety was 26.0% and 23.2%, respectively among COVID-19 survivors. The respondents who were ≥60 years were 2.62 and 3.02 times more likely to report depressive and anxiety symptoms, respectively than those aged 18 to 39 years. Hospitalised patients recovered from COVID-19 had a 2.18 times higher chance of developing anxiety than their non-hospitalised counterparts. COVID-19 recovered patients with comorbidities were at 3.35 and 2.97 times higher risk of depression and anxiety, respectively compared to those without comorbidities. Similarly, the respondents who had already passed a period of 15 days to 3 months after recovery showed 3.06 and 1.85 times higher odds of depression and anxiety, respectively than those who had already passed a period of above 3 to 6 months after recovery. Conclusion: The study reported a high prevalence of depression and anxiety among COVID-19 survivors living in Dhaka city. The findings suggest the need for appropriate interventions to reduce mental health complications in COVID-19 survivors.

Strengthening health service delivery and governance through institutionalizing 'Urban Health Atlas'-A geo-referenced Information Communication and Technology tool: Lessons learned from an implementation research in three cities in Bangladesh.

INTRODUCTION: Urban health governance in Bangladesh is complex as multiple actors are involved and no comprehensive data are currently available on infrastructure, services, or performance either in public and private sectors of the healthcare system. The Urban Health Atlas (UHA)-a novel and interactive geo-referenced, web-based visualization tool was developed in Bangladesh to provide geospatial and service information to decision makers involved in urban health service planning and governance. Our objective was to study the opportunities for institutionalization of the UHA into government health systems responsible for urban healthcare delivery and document the facilitators and barriers to its uptake. METHODS: This implementation research was carried out during 2017-2019 in three cities in Bangladesh: Dhaka, Dinajpur and Jashore. During the intervention period, six hands-on trainings on UHA were provided to 67 urban health managers across three study sites. Thirty in-depth and twelve key informant interviews were conducted to understand user experience and document stakeholder perceptions of institutionalizing UHA. RESULTS: Capacity building on UHA enhanced understanding of health managers around its utility for service delivery planning, decision making and oversight. Findings from the IDIs and KIIs suggest that UHA uptake was challenged by inadequate ICT infrastructure, shortage of human resources and lack of ICT skill among managers. Motivating key decision makers and stakeholders about the potential of UHA and engaging them from its inception helped the institutionalization process. CONCLUSION: While uptake of UHA by government health managers appears possible with dedicated capacity building initiatives, its use and regular update are challenged by multiple factors at the implementation level. A clear understanding of context, actors and system readiness is foundational in determining whether the institutionalization of health ICTs is timely, realistic or relevant.

Enhancing Fluorescence in Both Solution and Solid States Induced by Imine Cage Formation.

Developing luminescent materials that exhibit strong emissions in both solution and solid phases is highly desirable and challenging. Herein, we report imine-bond directed formation of a rigid organic cage (TPE-cage) that was synthesized by [2+4] imine condensation of a TPE-cored tetra-aldehyde (TPE-TA) with a clip-like diamine (XA) to illustrate confinement-induced fluorescence enhancement. Compared to the non-emissive TPE-TA (ϕF =0.26 %) in the dichloromethane (DCM) solution, the TPE-cage achieved a remarkable (~520-fold) emission enhancement (ϕF =70.38 %). In contrast, a monomeric tetra-imine model compound (TPE-model) showed only a minor enhancement (ϕF =0.56 %) in emission compared to the parent tetra-aldehyde TPE-TA. The emission of TPE-cage was further enhanced by ~1.5-fold (ϕF =80.96 %) in the aggregated state owing to aggregation-induced emission enhancement (AIEE). This approach establishes the potential for synthesizing luminescent materials with high emission in both solution and solid-state by employing a single-step imine condensation reaction.

Identification of Potential Aldose Reductase Inhibitors Using Convolutional Neural Network-Based in Silico Screening.

Aldose reductase (ALR2) is a notable enzyme of the polyol pathway responsible for aggravating diabetic neuropathy complications. The first step begins when it catalyzes the reduction of glucose to sorbitol with NADPH as a coenzyme. Elevated concentrations of sorbitol damage the tissues, leading to complications like neuropathy. Though considerable effort has been pushed toward the successful discovery of potent inhibitors, its discovery still remains an elusive task. To this end, we present a 3D convolutional neural network (3D-CNN) based ALR2 inhibitor classification technique by dealing with snapshots of images captured from 3D chemical structures with multiple rotations as input data. The CNN-based architecture was trained on the 360 sets of image data along each axis and further prediction on the Maybridge library by each of the models. Subjecting the retrieved hits to molecular docking leads to the identification of the top 10 molecules with high binding affinity. The hits displayed a better blood-brain barrier penetration (BBB) score (90% with more than four scores) as compared to standard inhibitors (38%), reflecting the superior BBB penetrating efficiency of the hits. Followed by molecular docking, the biological evaluation spotlighted five compounds as promising ALR2 inhibitors and can be considered as a likely prospect for further structural optimization with medicinal chemistry efforts to improve their inhibition efficacy and consolidate them as new ALR2 antagonists in the future. In addition, the study also demonstrated the usefulness of scaffold analysis of the molecules as a method for investigating the significance of structurally diverse compounds in data-driven studies. For reproducibility and accessibility purposes, all of the source codes used in our study are publicly available.

28-Homobrassinolide Primed Seed Improved Lead Stress Tolerance in Brassica rapa L. through Modulation of Physio-Biochemical Attributes and Nutrient Uptake.

Brassinosteroids (BRs) influence a variety of physiological reactions and alleviate different biotic and abiotic stressors. Turnip seedlings were grown with the goal of further exploring and expanding their function in plants under abiotic stress, particularly under heavy metal toxicity (lead stress). This study's objective was to ascertain the role of applied 28-homobrassinolide (HBL) in reducing lead (Pb) stress in turnip plants. Turnip seeds treated with 1, 5, and 10 µM HBL and were grown-up in Pb-contaminated soil (300 mg kg-1). Lead accumulation reduces biomass, growth attributes, and various biochemical parameters, as well as increasing proline content. Seed germination, root and shoot growth, and gas exchange characteristics were enhanced via HBL treatment. Furthermore, Pb-stressed seedlings had decreased total soluble protein concentrations, photosynthetic pigments, nutrition, and phenol content. Nonetheless, HBL increased chlorophyll a and chlorophyll b levels in plant, resulting in increased photosynthesis. As a result, seeds treated with HBL2 (5 µM L-1) had higher nutritional contents (Mg+2, Zn+2, Na+2, and K+1). HBL2-treated seedlings had higher DPPH and metal tolerance indexes. This led to the conclusion that HBL2 effectively reduced Pb toxicity and improved resistance in lead-contaminated soil.

Alleviation of salinity stress in zinc oxide nanoparticle-treated Lagenaria siceraria L. by modulation of physiochemical attributes, enzymatic and non-enzymatic antioxidative system.

Salt stress is a major abiotic stress that affects the world's agricultural soils and crop yield, the system that ensures food production. In the present study, three different concentrations of zinc oxide nanoparticles (250, 500 and 750ZnONPsmg L-1 ) were applied by soil drenching. The treatments aimed to improve the phytochemical characteristics of Lagenaria siceraria L. (bottle gourd) by lowering the oxidative stress brought on by salinity stress (200ppm NaF). Green synthesised ZnO NPs were prepared, having hexagonal and spherical shapes and sizes 16-35nm. Salt stress reduced fresh and dry biomass of plants and improved production of proline. ZnO NPs improved antioxidant response by enhancing catalase, ascorbate peroxidase, superoxide dismutase and peroxidase activities, and protecting cellular structures by eliminating free radicals and reactive oxygen species. The 500mg L-1 ZnO NPs treatment improved total chlorophyll (31%), total soluble sugars (23%) and maintained the gas exchange parameters under salt stress. This treatment also enhanced the biosynthesis of osmotic regulators (proline) by 19%, Na+ by 22% and Zn2+ by 17%, assisting mitigation of salt stress-mediated toxicity in plants. This study demonstrates that ZnO NP-treated seedlings show improved growth attributes, suggesting that ZnO NPs could be advantageous for L. siceraria cultivation in salt polluted areas and could be utilised in place of conventional Zn fertiliser for better crop yield.

Plant mediated fabrication of silver nanoparticles, process optimization, and impact on tomato plant.

Nanotechnology is one of the fastest-growing markets, but developing eco-friendly products, their maximum production, stability, and higher yield is a challenge. In this study, silver nanoparticles were synthesized using an easily available resource, leaves extract of the Neem (Azadirachta indica) plant, as a reducing and capping agent, determined their effect on germination and growth of tomato plants. The maximum production of silver nanoparticles was noted at 70 °C after 3 h of reaction time while treating the 10 ml leaf extract of Neem plant with 10 ml of 1 mM silver nitrate. The impact of the extract preparation method and solvent type on the plant mediated fabrication of silver nanoparticles was also investigated. The UV-spectrophotometric analysis confirmed the synthesis of silver nanoparticles and showed an absorption spectrum within Δ420-440 nm range. The size of the fabricated silver nanoparticles was 22-30 nm. The functional groups such as ethylene, amide, carbonyl, methoxy, alcohol, and phenol attached to stabilize the nanoparticles were observed using the FTIR technique. SEM, EDX, and XRD analyses were performed to study the physiochemical characteristics of synthesized nanoparticles. Silver nanoparticles increased the germination rate of tomato seeds up to 70% while decreasing the mean germination time compared to the control. Silver nanoparticles applied at varying concentrations significantly increased the shoot length (25 to 80%), root length (10 to 60%), and fresh biomass (10 to 80%) biomass of the tomato plant. The production of total chlorophyll, carotenoid, flavonoids, soluble sugar, and protein was significantly increased in tomato plants treated with 5 and 10 ppm silver nanoparticles compared to the control. Green synthesized silver nanoparticles are cost-effective and nontoxic and can be applied in agriculture, biomedical, and other fields.

Exogenous application of glutathione enhanced growth, nutritional orchestration and physiochemical characteristics of Brassica oleracea L. under lead stress.

A major obstacle to agricultural production and yield quality is heavy metal contamination of the soil and water, which leads to lower productivity and quality of crops. The situation has significantly worsened as a result of the growing population and subsequent rise in food consumption. The growth of nutrient-rich plants is hampered by lead (Pb) toxicity in the soil. Brassica oleracea L. (broccoli) is a prominent vegetable crop in the Brassicaceae family subjected to a number of biotic and abiotic stresses that dramatically lower crop yields. Seed priming is a novel, practicable, and cost-effective method that can improve various abiotic stress tolerances. Many plant metabolic activities depend on the antioxidant enzyme glutathione (GSH), which also chelates heavy metals. Keeping in view the stress mitigation potential of GSH, current research work was designed to inspect the beneficial role of seed priming with GSH on the growth, morphological and gas exchange attributes of broccoli seedlings under Pb stress. For this purpose, broccoli seeds were primed with 25, 50, and 75 µM L-1 GSH. Plant growth and photosynthetic activity were adversely affected by Pb stress. Furthermore, Pb stress enhanced proline levels along with reduced protein and phenol content. The application of GSH improved growth traits, total soluble proteins, chlorophyll content, mineral content, and gas exchange parameters. The involvement of GSH in reducing Pb concentrations was demonstrated by an improved metal tolerance index and lower Pb levels in broccoli plants. The results of the current study suggest that GSH can be used as a strategy to increase broccoli tolerance to Pb by enhancing nutrient uptake, growth and proline.

Dialysis capacity and nutrition care across Bangladesh: A situational assessment.

Hemodialysis (HD) is a treatment for ensuring the survival of end-stage kidney disease (ESKD) patients, and nutrition care is integral to their management. We sent questionnaires to evaluate the total dialysis service capacity and nutrition services across all dialysis facilities (DF) in Bangladesh, with responses from 149 out of 166 active DFs. Survey results revealed that 49.7% of DFs operated two shifts, and 42.3% operated three shifts daily, with 74.5% holding between one and ten dialysis machines. Sixty-three percent of DFs served between one and 25 patients per week, and 77% of patients received twice-weekly dialysis. The average cost for first-time dialysis was 2800 BDT per session (range: 2500-3000 BDT), but it was lower if reused dialyzers were used (2100 BDT, range: 1700-2800 BDT). Nutritionists were available in only 21% of the DFs. Parameters related to nutritional health screening (serum albumin, BMI, MIS-malnutrition inflammation assessment, and dietary intakes) were carried out in 37.6%, 23.5%, 2%, and 2% of the DFs, respectively, only if recommended by physicians. Nutrition education, if recommended, was provided in 68.5% of DFs, but only in 17.6% of them were these delivered by nutritionists. The recommendation for using renal-specific oral nutrition supplements (ONS) is not a familiar practice in Bangladeshi DFs and, therefore, was scarcely recommended. Dialysis capacity across Bangladesh is inadequate to meet current or projected needs and nutrition education and support across the DFs to benefit improving patients' quality of life is also inadequate.

TORC1 mediated regulation of mitochondrial integrity and calcium ion homeostasis by Wat1/mLst8 in S. pombe.

The mTOR complexes play a fundamental role in mitochondrial biogenesis and cellular homeostasis. Wat1, an ortholog of mammalian Lst8 is an important component of TOR complex and is essential for the regulation of downstream signaling. Earlier we reported the role of Wat1 in oxidative stress response. Here, we have shown that the abrogation of wat1 causes respiratory defects and mitochondrial depolarization that leads to a decrease in ATP production. The confocal and electron microscopy in wat1Δ cells revealed the fragmented mitochondrial morphology implying its role in mitochondrial fission. Furthermore, we also showed its role in autophagy and the maintenance of calcium ion homeostasis. Additionally, tor2-287 mutant cells also exhibit defects in mitochondrial integrity indicating the TORC1-dependent involvement of Wat1 in the maintenance of mitochondrial homeostasis. The interaction studies of Wat1 and Tor2 with Por1 and Mmm1 proteins revealed a plausible cross-talk between mitochondria and endoplasmic reticulum through the Mitochondria-associated membranes (MAM) and endoplasmic reticulum-mitochondria encounter structure (ERMES) complex, involving TORC1. Taken together, this study demonstrates the involvement of Wat1/mLst8 in harmonizing various mitochondrial functions, redox status, and Ca2+ homeostasis.

Selenium-Priming mediated growth and yield improvement of turnip under saline conditions.

Salt toxicity is one of the foremost environmental stresses that declines nutrient uptake, photosynthetic activity and growth of plants resulting in a decrease in crop yield and quality. Seed priming has become an emergent strategy to alleviate abiotic stress and improve plant growth. During the current study, turnip seed priming with sodium selenite (Na2SeO3) was investigated for its ability to mitigate salt stress. Turnip (Brassica rapa L. var. Purple Top White Globe) seeds primed with 75, 100, and 125 µML-1 of Se were subjected to 200 mM salt stress under field conditions. Findings of the current field research demonstrated that salt toxicity declined seed germination, chlorophyll content, and gas exchange characteristics of B. rapa seedling. Whereas, Se-primed seeds showed higher germination rate and plant growth which may be attributed to the decreased level of hydrogen peroxide (H2O2) and malondialdehyde (MDA) decreased synthesis of proline (36%) and besides increased total chlorophyll (46%) in applied turnip plants. Higher expression levels of genes encoding antioxidative activities (CAT, POD, SO,D and APX) mitigated oxidative stress induced by the salt toxicity. Additionally, Se treatment decreased Na+ content and enhanced K+ content resulting in elevated K+/Na+ ratio in the treated plants. The in-silico assessment revealed the interactive superiority of Se with antioxidant enzymes including CAT, POD, SOD, and APX as compared to sodium chloride (NaCl). Computational study of enzymes-Se and enzymes-NaCl molecules also revealed the stress ameliorative potential of Se through the presence of more Ramachandran-favored regions (94%) and higher docking affinities of Se (-6.3). The in-silico studies through molecular docking of Na2SeO3, NaCl, and ROS synthesizing enzymes (receptors) including cytochrome P450 (CYP), lipoxygenase (LOX), and xanthine oxidase (XO), also confirmed the salt stress ameliorative potential of Se in B. rapa. The increased Ca, P, Mg, and Zn nutrients uptake nutrients uptake in 100 µML-1 Se primed seedlings helped to adjust the stomatal conductivity (35%) intercellular CO2 concentration (32%), and photosynthetic activity (41%) resulting in enhancement of the yield attributes. More number of seeds per plant (6%), increased turnip weight (115 gm) root length (17.24 cm), root diameter (12 cm) as well as turnip yield increased by (9%tons ha-1) were recorded for 100 µML-1 Se treatment under salinity stress. Findings of the current research judiciously advocate the potential of Se seed priming for salt stress alleviation and growth improvement in B. rapa.

According to our best of knowledge, it is the first time that seed primed with Selenium have been evaluated regarding NaCl stress mitigation in turnip. Salinity toxicity negatively affected physiochemical activities and growth of B.rapa.Seed priming with Selenium (Na₂SeO₃) mitigated salinity stress.Selenium (Se) enhanced nutrition, photosynthetic and antioxidant activity of applied plants.Selenium treated plants exhibited improved growth and reduced salinity content.

Exploring media consumption and mental health among young adults during the second wave of COVID-19 in Bangladesh.

Background: This study examined the association between media exposure and mental health during the second wave of lockdown among the general population of Bangladesh. Methods: A total of 449 adult participants were enrolled in the study to evaluate their levels of exposure to total media, electronic media, and social media. Mental health was assessed using a 7-item generalized anxiety disorder (GAD-7) scale. A multivariate logistic regression model was constructed to explore the relationships between media exposure levels and anxiety. The models included covariates such as sex, daily working hours, health problems, media distraction, and income from social media. Results: The results showed that 44.5%, 39.2%, and 16.3% of participants reported low, medium, and high levels of exposure to different media during the COVID-19 period, respectively. Additionally, 96.4%, 2.7%, and 0.9% of participants had low, medium, and high levels of exposure to electronic media, respectively, and 89.1%, 10.5%, and 0.4% of participants had low, medium, and high levels of exposure to social media, respectively. The overall prevalence of anxiety was 25.38% among the respondents. Participants with high levels of total media exposure were significantly more likely to experience anxiety, with an odds ratio of 2.75 (95% CI = 1.40-5.14, p < 0.01). Females were 2.26 times more likely to experience anxiety than males (95% CI = 1.37-3.74, p < 0.01), and participants with health problems were also more likely to develop anxiety compared to those who did not. Conclusion: Our results show a positive relationship between increased media exposure and anxiety levels, providing useful insights for both academics and public health practitioners.

What is the optimal timing of surgery after short-course radiotherapy for rectal cancer?

BACKGROUND: Short-course neoadjuvant radiotherapy is a valuable tool in managing rectal cancers and has improved local recurrence rates. However, limited and conflicting data has resulted in variable usage and a lack of consensus on the optimal timing of surgery following short-course radiotherapy. This review aims to provide a contemporary summation of the available evidence regarding the optimal time interval between short-course neoadjuvant radiotherapy and surgery. METHODS: A focused literature search was undertaken using the PubMed and Embase databases from January 1980 until January 2023. Randomised control trials, large observational studies and systematic reviews focusing on the use of short-course preoperative radiotherapy for localised rectal cancers, with a focus on the timing of surgery, were included. Primary outcomes were overall survival, disease-free survival and perioperative complications. RESULTS: Five randomised control trials, two meta-analyses, and two large, population-based studies were included for their eligibility and relevance. Increased downstaging and fewer postoperative complications are demonstrated in patients receiving delayed surgery (> four weeks), but more recent data raise concerns regarding increased rates of local recurrence in this cohort. Studies directly comparing different time intervals to surgery following short-course radiotherapy have failed to demonstrate an effect on overall survival. CONCLUSIONS: This review highlights the complexities and relative shortcomings of the available data with few high-quality studies and randomised control trials directly comparing different time intervals to surgery following short-course radiotherapy. Continuing research is needed to confirm existing findings and explore gaps in the current literature.

Glutathione primed seed improved lead-stress tolerance in Brassica rapa L. through modulation of physio-biochemical attributes and nutrient uptake.

Heavy metal toxicity is a major environmental issue that affects all life forms, including plants. The accumulation of lead (Pb) in agricultural soils is a significant contributor to reduced crop yields, and it poses serious health risks to people who consume lead-contaminated agricultural products. The current study was undertaken to investigate the beneficial effects of glutathione (GSH) on the amelioration of stress induced by Pb (300 mg kg-1 Pb) in Brassica rapa L. (turnip). For this purpose, B. rapa seeds primed with 25, 50, and 75 µmol L-1. The root and shoot length, seedling biomass, and leaf area, was reduced under Pb stress. Lead toxicity inhibited the net photosynthetic rate (31.36%), total chlorophyll content (74.54%) of B. rapa plants in comparison to control. Lead-stressed plants additionally exhibited changes in proline levels, as well as lower levels of total soluble protein and phenolic content. Nevertheless, seed priming with GSH resulted in higher concentrations of the nutritional content (Mg+2, Zn+2, Na+, K+) that increased Pb stress tolerance. The GSH2 treated seed enhanced the photosynthetic rate (46.34%), stomatal conductance (80.55%), and transpiration rate (53.125%) over Pb stress. Furthermore, GSH2 enhanced total soluble proteins (37.75%), phenolic content (58.38%), and DPPH (1.5fold) of turnip plant over control seedlings. According to our research, GSH2 primed B. rapa seed demonstrated a reduction in Pb toxicity, which could be used to help seedling establishment in soils contaminated with Pb.

Numerous studies highlight the advantages of plant growth regulators for agricultural crop development and productivity. Nevertheless, we know remarkably little about the role of glutathione as a seed-priming agent in vegetable crops. Additionally, little is known about how glutathione affects the physiological traits, nutrient content, and growth of B. rapa L. (turnip) under lead stress. Therefore, the goal of this work was to evaluate how exogenously applied glutathione improved the agronomic traits, physiochemical characteristics, and nutrient content of B. rapa L. under lead stress.

Mitigation of chromium-induced phytotoxicity in 28-homobrassinolide treated Trigonella corniculata L. by modulation of oxidative biomarkers and antioxidant system.

Chromium (Cr) is one of the toxic heavy metals that disturbs growth and physiological properties of plants. During the current study, Trigonella corniculata L. (Fenugreek) was exposed to different levels of Cr in potted soil. Chromium toxicity reduced fiber, ash, moisture, carbohydrate, protein, fats, and flavonoid content of T. corniculata. Considering the stress relieving effect of 28-homobrassinolide (28-HBR), seeds of T. corniculata were primed with different concentration of 28-HBR i.e., 0, 5, 10, and 20 µmol L-1. Application of 28-HBR reversed the toxic effect of Cr through improvement in activity of antioxidant enzymes like superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT). Conclusively, 10 µmol L-1 28-HBR increased Cr tolerance in T. corniculata seedlings due to reduction in oxidative stress markers. It is further proposed that 28-HBR is an effective stress ameliorant to relive plants from various abiotic stresses.

The role of iron in the pathogenesis of endometriosis: a systematic review.

STUDY QUESTION: What is the role of iron in the pathophysiology of endometriosis? SUMMARY ANSWER: Iron excess is demonstrated wherever endometriotic tissues are found and is associated with oxidative stress, an inflammatory micro-environment, and cell damage; the iron-mediated oxidative stress is independently linked to subfertility, symptom severity, and malignant transformation. WHAT IS KNOWN ALREADY: Iron is found in excess in endometriotic tissues, and multiple mechanisms have been studied and posited to explain this. It is clear that iron excess plays a vital role in promoting oxidative stress and cell damage. The evidence base is large, but no comprehensive reviews exist to summarize our understanding and highlight the overarching themes to further our understanding and suggest future directions of study for the field. STUDY DESIGN SIZE DURATION: This systematic review with a thematic analysis retrieved studies from the PubMed, Embase, Web of Science, and Cochrane Library databases and searches were conducted from inception through to August 2022. Human and animal studies published in the English language were included and identified using a combination of exploded MeSH terms ('Iron' and 'Endometriosis') and free-text search terms ('Iron', 'Ferric', 'Ferrous', 'Endometriosis', 'Endometrioma'). PARTICIPANTS/MATERIALS SETTING METHODS: This review was reported in accordance with the PRISMA guidelines. All studies reporting original data concerning the role of iron or iron complexes in the pathophysiology of endometriosis were included. Studies that did not report original data or provided a review of the field were excluded. Bias analysis was completed for each included study by using the Newcastle-Ottawa scoring system. MAIN RESULTS AND THE ROLE OF CHANCE: There were 776 records identified and these were screened down to 53 studies which met the eligibility criteria, including 6 animal and 47 human studies, with 3556 individual participants. Iron excess is demonstrated in various tissues and fluids, including ovarian endometriomas, ovarian follicles, ectopic endometriotic lesions, and peritoneal fluid. Markers of oxidative stress are strongly associated with high iron levels, and aberrant expression of iron-transport proteins has been demonstrated. Abnormal resistance to ferroptosis is likely. Iron-mediated oxidative stress is responsible for a pro-inflammatory micro-environment and is linked to subfertility, symptom severity, and, possibly, malignant transformation. LIMITATIONS REASONS FOR CAUTION: A minority of the included studies were of objectively low quality with a high risk of bias and may lead to misleading conclusions. Additionally, multiple studies failed to appropriately characterize the included patients by known confounding variables, such as menstrual cycle phase, which may introduce bias to the findings. WIDER IMPLICATIONS OF THE FINDINGS: Current literature depicts a central role of aberrant iron mechanics and subsequent oxidative stress in endometriosis. It is likely that iron excess is at least partly responsible for the persistence and proliferation of ectopic endometriotic lesions. As such, iron mechanics represent an attractive target for novel therapeutics, including iron chelators or effectors of the iron-oxidative stress pathway. There are significant gaps in our current understanding, and this review highlights and recommends several topics for further research. These include the role of iron chelation, resistance to ferroptosis, the relationship between iron excess and localized hypoxia, systemic iron pathophysiology in endometriosis, and the role of oxidative stress in malignant transformation. STUDY FUNDING/COMPETING INTERESTS: J.W. and S.G.P. are supported by clinical fellowships at Liverpool University Hospital NHS Foundation trust. No additional funding was requested or required for the completion of this work. C.J.H. is supported by a Wellbeing of Women project grant (RG2137). D.K.H. is supported by a Wellbeing of Women project grant (RG2137) and an MRC clinical research training fellowship (MR/V007238/1). The authors have no conflicts of interest to declare. REGISTRATION NUMBER: A protocol was prospectively registered with the PROSPERO database in August 2021 (CRD42021272818).

Identification of novel TACE inhibitors using DNN based- virtual screening, molecular dynamics and biological evaluation.

Rheumatoid Arthritis (RA) is a well-known autoimmune inflammatory disease, distressing roughly 1% of the adult population throughout the globe. Many studies have suggested that overexpression of TNF-α, a pro-inflammatory cytokine, is responsible for the progression of RA. Furthermore, inhibition of the shedding rate of TNF-α is regulated by the TACE (TNF-α converting enzyme) protein and, hence is considered as an important therapeutic target for the prevention of progressive synovial joint destruction in rheumatoid arthritis. In the present study, we have proposed a deep neural network (DNN)-based workflow for the virtual screening of compounds towards the identification of potential inhibitors against the TACE proteins. Subsequently, a set of compounds were shortlisted, based on the molecular docking and subjected to the biological evaluation to validate the inhibitory activities of the screened compounds, determine the practical applicability of the DNN-based model, and strengthen the hypothesis. Out of seven, three compounds (BTB10246, BTB10247, and BTB10245) showed significant inhibition at 10 µM and 0.1 µM concentration. These three compounds also showed a stable and significant interaction potential against the TACE protein as compared with the re-docked complex system and can serve as a novel scaffold for further design of new molecules with improved inhibitory activities against TACE.Communicated by Ramaswamy H. Sarma.

Vascularisation in Deep Endometriosis: A Systematic Review with Narrative Outcomes.

Deep endometriosis (DE) is the most severe subtype of endometriosis, with the hallmark of lesions infiltrating adjacent tissue. Abnormal vascularisation has been implicated in contributing to endometriosis lesion development in general, and how vascularisation influences the pathogenesis of DE, in particular, is of interest. This systematic review followed the PRISMA guidelines to elucidate and examine the evidence for DE-specific vascularisation. A literature search was performed using MEDLINE, Embase, PubMed, Scopus, Cochrane CENTRAL Library and Europe PubMed Central databases. The databases were searched from inception to the 13 March 2023. A total of 15 studies with 1125 patients were included in the review. The DE lesions were highly vascularised, with a higher microvessel density (MVD) than other types of endometriotic lesions, eutopic endometrium from women with endometriosis and control tissue. Vascular endothelial growth factor, its major subtype (VEGF-A) and associated receptor (VEGFR-2) were significantly increased in the DE lesions compared to superficial endometriosis, eutopic endometrium and control tissue. Progestin therapy was associated with a significant decrease in the MVD of the DE lesions, explaining their therapeutic effect. This review comprehensively summarises the available literature, reporting abnormal vascularisation to be intimately related to the pathogenesis of DE and presents potentially preferential therapeutic targets for the medical management of DE.