Classification of e-waste using machine learning-assisted laser-induced breakdown spectroscopy.

Waste management and the economy are intertwined in various ways. Adopting sustainable waste management techniques can contribute to economic growth and resource conservation. Artificial intelligence (AI)-based classification is very crucial for rapid and contactless classification of metals in electronic waste (e-waste) management. In the present research work, five types of aluminium alloys, because of their extensive use in structural, electrical and thermotechnical functions in the electronics industry, were taken. Laser-induced breakdown spectroscopy (LIBS), a spectral identifier technique, was employed in conjunction with machine learning (ML) classification models of AI. Principal component analysis (PCA), an unsupervised ML classifier, was found incapable to differentiate LIBS data of alloys. Supervised ML classifier was then trained (for 10-fold cross-validation) on randomly selected 80% and tested on 20% spectral data of each alloy to assess classification capacity of each. In most of the tested variants of K nearest neighbour (kNN) the resulting accuracy was lower than 30% but kNN ensembled with random subspace method showed improved accuracy up to 98%. This study revealed that an AI-based LIBS system can classify e-waste alloys rather effectively in a non-contactless mode and could potentially be connected with robotic systems, hence, minimizing manual labour.

New 1,3,4-Thiadiazole Derivatives as α-Glucosidase Inhibitors: Design, Synthesis, DFT, ADME, and In Vitro Enzymatic Studies.

Diabetes is an emerging disorder in the world and is caused due to the imbalance of insulin production as well as serious effects on the body. In search of a better treatment for diabetes, we designed a novel class of 1,3,4-thiadiazole-bearing Schiff base analogues and assessed them for the α-glucosidase enzyme. In the series (1-12), compounds are synthesized and 3 analogues showed excellent inhibitory activity against α-glucosidase enzymes in the range of IC50 values of 18.10 ± 0.20 to 1.10 ± 0.10 µM. In this series, analogues 4, 8, and 9 show remarkable inhibition profile IC50 2.20 ± 0.10, 1.10 ± 0.10, and 1.30 ± 0.10 µM by using acarbose as a standard, whose IC50 is 11.50 ± 0.30 µM. The structure of the synthesized compounds was confirmed through various spectroscopic techniques, such as NMR and HREI-MS. Additionally, molecular docking, pharmacokinetics, cytotoxic evaluation, and density functional theory study were performed to investigate their behavior.

Effectiveness of digital tools for smoking cessation in Asian countries: a systematic review.

AIM: The use of tobacco is responsible for many preventable diseases and deaths worldwide. Digital interventions have greatly improved patient health and clinical care and have proven to be effective for quitting smoking in the general population due to their flexibility and potential for personalization. However, there is limited evidence on the effectiveness of digital interventions for smoking cessation in Asian countries. METHODS: Three major databases - Web of Science (WOS), Scopus, and PubMed - for relevant studies published between 1 January 2010 and 12 February 2023 were searched for studies evaluating the effectiveness of digital intervention for smoking cessation in Asian countries. RESULTS: A total of 25 studies of varying designs were eligible for this study collectively involving a total of n = 22,005 participants from 9 countries. Among different digital tools for smoking cessation, the highest abstinence rate (70%) was reported with cognitive behavioural theory (CBT)-based smoking cessation intervention via Facebook followed by smartphone app (60%), WhatsApp (59.9%), and Pharmacist counselling with Quit US smartphone app (58.4%). However, WhatsApp was preferred over Facebook intervention due to lower rates of relapse. WeChat was responsible for 15.6% and 41.8% 7-day point prevalence abstinence. For telephone/text messaging abstinence rate ranged from 8-44.3% and quit rates from 6.3% to 16.8%. Whereas, no significant impact of media/multimedia messages and web-based learning on smoking cessation was observed in this study. CONCLUSION: Based on the study findings the use of digital tools can be considered an alternative and cost-effective smoking cessation intervention as compared to traditional smoking cessation interventions.

Evaluation of healthcare professionals' understanding of fluoroquinolones' safety profile, usage, and boxed warnings in Pakistan.

INTRODUCTION: Fluoroquinolones (FQs) is a distinct class of antibiotics which are prescribed and used quite frequently worldwide, despite the box warnings (BW) issued by Food and Drug Administration (FDA). Literature has shown in spite of BWs related to FQs there is minimal impact on health care professionals (HCPs) prescribing habits, potentially attributing towards limited and insufficient awareness. In Pakistan, FQs are mostly prescribed antibiotics for microbial treatments, therefore the purpose of this study was to determine the level of knowledge about the safety profile, use, and BW of FQs among HCPs working in Pakistan. METHODS: A cross-sectional study was undertaken among the HCPs of Khyber Pakhtunkhwa province of Pakistan from October 2022 to December 2022. A validated questionnaire was used to assess the knowledge of HCPs regarding FQs, its safety profile and BW. A random convenient sample technique was used while recruiting HCPs in this study. As the HCPs comprised physicians, dentists, pharmacist and nurses, all were approached in person and the study objective was fully elaborated and explained to them. The statistic test like: one-way ANOVA, independent-t test, multivariate logistic regression were used keeping the p-value < 0.05 as statistically significant. RESULTS: A total of n = 250 HCPs were approached, of which n = 186 HCPs completed the questionnaire with a response rate of 74.4%. FQs prescribing pattern was only assessed among the prescribers, i.e., physicians and dentists (39/186). The mean knowledge score for indications was 5.29 ± 3.05, while for the adverse effects was 7.70 ± 2.61. The highest score for knowledge for indications and adverse effect score was achieved by physicians followed by dentist. The mean knowledge score for the BW was 3.46 ± 2.93 and among the HCPs for the BW of FQs, 20.4% of the HCPs had appropriate knowledge score (score ≥ 50%). The knowledge score was significantly higher in males (p = 0.039), dentists (p = 0.001), HCPs having master/specialization level of education (p = 0.003), HCPs working in government sector hospitals (p = 0.010) and secondary care hospitals (p = 0.001) while the multivariate logistic regression analysis showed that HCPs working in primary care hospital (OR: 6.2) and secondary care hospital (OR: 20.3) were associated with the tendency to achieve 50% or above knowledge score. CONCLUSION:  Findings of this study reveals the unsatisfactory knowledge of HCPs regarding the safety profile, use, and BW of FQs putting patients at heightened risks of FQs associated AEs. Therefore, it is crucial to implement a national antimicrobial stewardship program, seminars and lectures aimed at continuously updating the knowledge of HCPs, regardless of their specialties, and effectively restrict the misuse of antimicrobial and disseminate FDA BWs in clinical practice.

Knowledge, attitude and perceptions of pharmacists regarding renal dose adjustment among chronic kidney disease patients in Pakistan.

BACKGROUND: Chronic kidney disease (CKD) poses a significant public health challenge. CKD patients have compromised renal function, which not only alters the pharmacokinetics of drugs but also their pharmacodynamics. Adjusting drug doses for these patients is essential to achieve the intended clinical outcomes, prevent adverse drug events, and halt further progression of the disease. Pharmacists play a pivotal role in ensuring safe and appropriate therapy for CKD patients. However, there is a noticeable absence of national dosing guidelines for CKD in Pakistan, coupled with a scarcity of studies exploring the knowledge, attitude, and perception of renal dose adjustments in the country. This study aimed to evaluate the knowledge, attitudes, and perceptions of pharmacists in the Khyber Pakhtunkhwa province and Islamabad regarding renal dose adjustments. METHODOLOGY: A cross-sectional study was conducted to gauge the knowledge, attitude, and perception of pharmacists working in various cities of Khyber Pakhtunkhwa and the capital city, Islamabad, from February to May 2023. The Renal Dosing Questionnaire-13 (RDQ-13) scale was employed for this purpose. The survey link was disseminated through emails, and the RDQ-13 scale was also completed in person by pharmacists from hospitals, clinics, community, and retail settings who interact with CKD patients. Univariate linear regression was employed, and factors with a p value < 0.25 were subjected to multivariate linear regression. For comparing knowledge, attitude, and perception scores of pharmacists, the independent t test and one-way ANOVA were utilized as appropriate. A p value < 0.05 was deemed statistically significant. RESULTS: Of the 384 pharmacists approached, 270 completed the RDQ-13 scale, resulting in a response rate of 70.3%. The overall knowledge score regarding renal dose adjustment was 21.24 ± 2.18 (mean ± SD). Attitude scores averaged at 10.04 ± 1.81, and perception scores at 7.19 ± 2.15. Multivariate analysis indicated a positive correlation between the pharmacists' perception scores and gender, with male pharmacists scoring higher than their female counterparts. CONCLUSIONS: The study underscores the importance of instituting targeted training programs for pharmacists, ensuring access to dependable resources, and promoting research and results dissemination in the realm of renal pharmacotherapy to enhance public health outcomes.

Long-term clinical efficacy and safety of thalidomide in patients with transfusion-dependent ß-thalassemia: results from Thal-Thalido study.

Regular blood transfusion is the mainstay of treatment in transfusion-dependent ß-thalassemia (TDT); however, transfusions culminate in an array of serious complications. Therefore, a single-arm, non-randomized clinical trial was conducted in hydroxyurea refractory TDT patients to explore the long-term safety and efficacy of thalidomide. The primary outcomes for efficacy were rise in hemoglobin (Hb) level and changes in transfusion frequency. Whereas, several clinical and laboratory parameters were assessed for safety of thalidomide. Secondary outcomes included changes in serum ferritin, serum lactate dehydrogenase (LDH), serum uric acid, red blood cell indices, and size of liver and spleen. A total of 532 patients were followed for a period of 30 months. Significant increase in mean Hb level was identified at 6 months (1.4 g/dL, p ≤ 0.001) and 30 months (2 g/dL, p ≤ 0.001) in comparison with baseline. A total of 408 (76.7%) patients responded to thalidomide therapy (excellent responders 25.8%, good responders 31%, and partial responders 19.9%) and attained transfusion independence within 6 months of therapy. A significant decline in mean ferritin, LDH level, liver size, and spleen size was observed. No unfavorable effects were observed on kidney and liver functions. Mild adverse events were reported in 48 (9%) patients and serious adverse events, including cerebral vascular accident and portal vein thrombosis were reported in two patients each. This study concludes that thalidomide is an effective and well-tolerated drug that can improve Hb levels and reduce transfusion burden in hydroxyurea refractory TDT patients.Trial registration: This trial is registered at http://www.clinicaltrial.gov as # NCT03651102.

Can Pharmacists' Counseling Improve the Use of Inhalers and Quality of Life? A Prospective "Pre" and "Post" Education Analysis in Mardan, Pakistan.

Introduction: Asthma is one of the common major non-communicable respiratory diseases, and is associated with a lower health-related quality of life (QOL). Poor inhalation is a significant contributing factor to poor control of asthma. Community pharmacist has a vital role to play in assisting patients and ultimately improving their asthma conditions through the use of inhalers. Aim: This study aimed to assess the effectiveness of "pre" and "post" educational intervention by a community pharmacist within a community pharmacy on asthma patients' QOL, inhaler technique, and adherence to therapy during the endemic phase of COVID-19. Methods: A "pre" and "post" interventional study was performed at a community pharmacy in the city of Mardan, Pakistan, in 2022 during the COVID-19 pandemic. Patients were divided into two groups, ie control and pharmacist-led education groups. After assigning patients to both groups, the baseline data were collected and followed for one month to compare the reduction in errors in the use of inhalers, QOL, and adherence to therapy. A paired sample t-test was performed, keeping a p-value <0.05 as statistical significance. Results: A total of 60 patients were recruited, majority (58.3%) were females, and 28.3% were from the age group of 46-55 years old. A statistically significant difference was observed in the pre- and post-education QOL score among patients in the pharmacist-led education group, from a mean ± SD at pre-education of 40.23±10.03 to a mean±SD at post-education of 48.10±5.68. Similarly, a statistically significant difference was observed for the correct use of inhalers, ie MDIs and DPIs. Similarly, a statistically significant difference was observed in the adherence status between pre-education and post-education by pharmacists. Conclusion: The findings of the study revealed a positive impact of community pharmacist-led education on QOL, inhaler technique, and adherence to therapy among patients with asthma.

Molecular Modeling and Synthesis of Indoline-2,3-dione-Based Benzene Sulfonamide Derivatives and Their Inhibitory Activity against α-Glucosidase and α-Amylase Enzymes.

Diabetes is also known as a critical and noisy disease. Hyperglycemia, that is, increased blood glucose level is a common effect of uncontrolled diabetes, and over a period of time can cause serious effects on health such as blood vessel damage and nervous system damage. However, many attempts have been made to find suitable and beneficial solutions to overcome diabetes. Considering this fact, we synthesized a novel series of indoline-2,3-dione-based benzene sulfonamide derivatives and evaluated them against α-glucosidase and α-amylase enzymes. Out of the synthesized sixteen compounds (1-16), only three compounds showed better results; the IC50 value was in the range of 12.70 ± 0.20 to 0.90 ± 0.10 µM for α-glucosidase against acarbose 11.50 ± 0.30 µM and 14.90 ± 0.20 to 1.10 ± 0.10 µM for α-amylase against acarbose 12.20 ± 0.30 µM. Among the series, only three compounds showed better inhibitory potential such as analogues 11 (0.90 ± 0.10 µM for α-glucosidase and 1.10 ± 0.10 µM for α-amylase), 1 (1.10 ± 0.10 µM for α-glucosidase and 1.30 ± 0.10 µM for α-amylase), and 6 (1.20 ± 0.10 µM for α-glucosidase and 1.60 ± 0.10 µM for α-amylase). Molecular modeling was performed to determine the binding affinity of active interacting residues against these enzymes, and it was found that benzenesulfonohydrazide derivatives can be indexed as suitable inhibitors for diabetes mellitus.

First principles calculation to investigate the effect of Mn substitution on Cu site in CeCu3-x Mn x V4O12 (x = 0, 1, 2 and 3) system.

Structural, electronic, elastic and magnetic properties of CeCu3-x Mn x V4O12 (x = 0, 1, 2 and 3) system have been carried out through DFT using GGA, GGA+U and HF potential. The investigation of structural optimization reveals that lattice parameters of the understudy system is reliable with the reported results and are increasing with the Mn substitution due to their greater atomic radii as compare to Cu atom. Both the cohesive energy and the enthalpy show that CeCu3V4O12 is the most thermodynamically stable among these compounds. When Mn is replaced by Cu in these compounds, not only it become semi-metals, but the host compound also changes from non-magnetic to anti-ferromagnetic and their electrical resistance provides further credence to their electronic behavior. Mechanical stability, anisotropy, and ductility are all demonstrated through the elastic characteristics of these compounds. Due to anti-ferromagnetic ductile nature of the Mn base compounds, it is expected that the compounds in the system may use for spintronic application and in magnetic cloaking devices.

Polymeric Membranes of Chitosan/Aloe Vera Gel Fabrication With Enhanced Swelling and Antimicrobial Properties for Biomedical Applications.

Since ancient times, medicinal plants have been used as traditional medicine to treat a variety of ailments. Aloe vera (AV) gel's therapeutic potential is one of the most effective approach in the fabrication of functional materials. The current study aimed to prepare the AV and chitosan (CS) membranes using various cross-linkers that were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform-infrared (FT-IR) spectroscopy, thermal gravimetric analysis (TGA), and ultraviolet-visible (UV-Visible) techniques, as well as swelling ratio and antimicrobial studies. SEM analysis revealed that the membrane is porous, with interconnected pores. The inclusion of AV contents in the membrane improved thermal stability and crystallinity. The swelling ratio of the ACPG-3 membrane with a 2:1 CS to AV ratio was 366%. The membranes showed promising antimicrobial activity against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Pasteurella multocida strains. The findings revealed that polymeric CS/AV membranes have effective potential for use in the biomedical field.

Biochemical analysis, photosynthetic gene (psbA) down-regulation, and in silico receptor prediction in weeds in response to exogenous application of phenolic acids and their analogs.

Chemical herbicides are the primary weed management tool, although several incidences of herbicide resistance have emerged, causing serious threat to agricultural sustainability. Plant derived phenolic acids with herbicidal potential provide organic and eco-friendly substitute to such harmful chemicals. In present study, phytotoxicity of two phenolic compounds, ferulic acid (FA) and gallic acid (GA), was evaluated in vitro and in vivo against three prevalent herbicide-resistant weed species (Sinapis arvensis, Lolium multiflorum and Parthenium hysterophorus). FA and GA not only suppressed the weed germination (80 to 60% respectively), but also negatively affected biochemical and photosynthetic pathway of weeds. In addition to significantly lowering the total protein and chlorophyll contents of the targeted weed species, the application of FA and GA treatments increased levels of antioxidant enzymes and lipid peroxidation. Photosynthetic gene (psbA) expression was downregulated (10 to 30 folds) post 48 h of phenolic application. In silico analysis for receptor identification of FA and GA in psbA protein (D1) showed histidine (his-198) and threonine (thr-286) as novel receptors of FA and GA. These two receptors differ from the D1 amino acid receptors which have previously been identified (serine-264 and histidine-215) in response to PSII inhibitor herbicides. Based on its toxicity responses, structural analogs of FA were also designed. Four out of twelve analogs (0.25 mM) significantly inhibited weed germination (30 to 40%) while enhancing their oxidative stress. These results are unique which provide fundamental evidence of phytotoxicity of FA and GA and their analogs to develop cutting-edge plant based bio-herbicides formulation in future.

Multifunctional Iron Oxide Nanocarriers Synthesis for Drug Delivery, Diagnostic Imaging, and Biodistribution Study.

The aim of the current study is to design the radiolabeled and drug-loaded nanocarrier with high loading capacity and pH-dependent drug release characteristics that could effectively transport loaded compounds to various organs for efficient diagnostic imaging and chemotherapeutic drug delivery. The aqueous extract of green tea leaves was used to synthesize the small-sized iron oxide nanoparticles (IONPs). The nanoparticles were characterized with UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray analysis (EDX). Iron oxide nanoparticles with sizes smaller than 50 nm were successfully synthesized, making them suitable for in vivo studies. In drug loading trials, 94% of the drug was loaded onto the active surface of iron oxide nanoparticles from the solution. The in vitro drug release study revealed that an acidic environment (pH 4.5) effectively triggers the release of doxorubicin (DOX) from the nanoparticles as compared to a neutral environment (pH 7.4). The gamma-emitting radionuclide 99mTc was successfully labeled with IONPs for biodistribution and imaging studies. The efficiency of radiolabeling was observed to be ≥ 99%. Furthermore, the in vivo biodistribution study of radiolabeled IONPs in rabbit model showed rapid accumulation in various organs such as heart, liver, and kidneys. This work suggested that green synthesized iron oxide nanoparticles are potential nanocarriers for diagnostic imaging and efficiently distributing DOX to specific organs. The aqueous extract of green tea leaves was used for the facile green synthesis of iron oxide nanoparticles (IONPs). Furthermore, the chemotherapeutic drug doxorubicin (DOX) and gamma-emitting radionuclide 99mTc were loaded on these iron oxide nanoparticles to evaluate the in vivo biodistribution and drug delivery studies in the rabbit models.

Does financial transparency substitute corporate governance to improve stock liquidity? Evidence from emerging market of Pakistan.

The aim of this study is to empirically analyze the impact of corporate governance on stock liquidity and the moderating role of financial transparency, through the lens of information asymmetry and agency theory. The sample consists of non-financial firms listed on the Pakistan stock exchange during the 2009-2019 period. The study used an instrumental variable approach and new corporate governance index, developed with principal component analysis, to demonstrate a relationship between corporate governance and stock liquidity. The results show a significant, positive relationship between the corporate governance index and stock liquidity, suggesting that well governed firms have high liquidity. To the best of our knowledge, this is the first finance study to investigate the moderating impact of financial transparency on the relation between corporate governance and stock liquidity. The results show that financial transparency, as measured by multiple proxies, has a negative moderating impact on the relationship between corporate governance and stock liquidity, suggesting that corporate governance in Pakistan is weak. Together, the results suggest that Pakistani firms use financial transparency as a substitute for corporate governance to improve stock liquidity. The results are robust to a series of endogeneity checks using alternative proxies of stock liquidity.

Mechanically Stable Magnetic Metallic Materials for Biomedical Applications.

The structural, electrical, and magneto-elastic properties of lanthanide base nitride (Ln = Dy-Lu) anti-perovskites were investigated using density functional theory (DFT). The reported structural outcomes are consistent with the experiment and decrease from Dy to Lu due to the decrease ofatomic radii of Ln atoms. According to the electronic band profile, the metallic characteristics of these compounds are due to the crossing over of Ln-f states at the Fermi level and are also supported by electrical resistivity. The resistivity of these compounds at room temperature demonstrates that they are good conductors. Their mechanical stability, anisotropic, load-bearing, and malleable nature are demonstrated by their elastic properties. Due to their metallic and load-bearing nature, in addition to their ductility, these materials are suitable as active biomaterials, especially when significant acting loads are anticipated, such as those experienced by such heavily loaded implants as hip and knee endo-prostheses, plates, screws, nails, dental implants, etc. In thesecases, appropriate bending fatigue strength is required in structural materials for skeletal reconstruction. Magnetic properties show that all compounds are G-type anti-ferromagnetic, with the Neel temperatures ranging from 24 to 48 K, except Lu3Nin, which is non-magnetic. Due to their anti-ferromagnetic structure, magnetic probes cannot read data contained in anti-ferromagnetic moments, therefore, data will be unchanged by disrupted magnetic field. As a result, these compounds can be the best candidates for magnetic cloaking devices.

Are owners chalk and cheese in the context of dividend smoothing asymmetry?

The study analyzes the impact of ownership structure on dividend smoothing via the lens of agency and information asymmetry theory. The study also investigates the impact of ownership on dividend smoothing in the unexamined asymmetric context Dividend smoothing is measured via speed of adjustment and relative volatility. The study documents that higher individual, management, and institutional ownerships are positively associated with increased dividend smoothing. Consistent with the rental hypothesis in foreign-owned firms smooth less also concentrated firms bear with cuts and omissions. Foreign ownership has the opposite impact on dividend smoothing in adjusting dividends from below and above i.e., always prefer high dividends. Individual ownership has also exhibited a different impact in smoothing from below and above. Institutional owners avoid cuts and omissions and negatively affect SOA (smooth more) in case of adjusting dividends from above. Ownership concentration is negatively associated with dividend smoothing irrespective of whether the firm is smoothing from above or below. In contrast, management ownership negatively affected SOA in adjusting from above or below. Family firms in Pakistan smooth more to win minor shareholders' trust and signal that they sacrifice their private benefits to reduce the type II agency problem. Finally, the authors found a negative association between dividend smoothing and corporate governance quality. Over all the findings of the current study provides insight to the investors and regulators by offering dividend smoothing as an alternative monitoring mechanism to corporate governance.

Does institutional quality moderate the relationship between corporate governance and stock liquidity? Evidence from the emerging market of Pakistan.

The main aim of this study was to empirically analyze whether Institutional Quality moderates the relationship between corporate governance and stock liquidity through the light of agency and information asymmetry theory. To the best of our knowledge, this is the first finance study. The sample consists of 230 non-financial firms listed on the Pakistan stock exchange during the period of 2009-2019. We used an instrumental variable approach and our new Institutional Quality index composed of world governance indicators and a corporate governance index, developed via principal component analysis, to demonstrate a relationship between corporate governance and stock liquidity and check the moderating role of Institutional Quality by following the resources complementary phenomenon. Our results show a significant, positive relationship between the corporate governance index and stock liquidity, suggesting that well-governed firms have high liquidity. The results show that the Institutional Quality index has a positive moderating impact on the relationship between corporate governance and stock liquidity, suggesting that corporate governance in Pakistan is weak. Our results are robust to a series of endogeneity checks using alternative proxies of stock liquidity.

In-silico Studies Calculated a New Chitin Oligomer Binding Site Inside Vicilin: A Potent Antifungal and Insecticidal Agent.

Vicilins are major seed storage proteins and show differential binding affinities toward sugar moieties of fungal cell wall and insect gut epithelium. Hence, purpose of study is the thorough in-silico characterization of interactions between vicilin and chitin oligomer followed by fungal and insecticidal bioassays. This work covers the molecular simulation studies explaining the interactions between Pisum sativum vicilin (PsV) and chitin oligomer followed by protein bioassay against different pathogens. LC-MS/MS of purified PsV (∼50 kDa) generated residual data along high pea vicilin homology (UniProtKB ID; P13918). Predicted model (PsV) indicated the characteristic homotrimer joined through head-to-tail association and each monomer is containing a bicupin domain. PsV site map analysis showed a new site (Site 4) into which molecular docking confirmed the strong binding of chitin oligomer (GlcNAc)4. Molecular dynamics simulation data (50 ns) indicated that chitin-binding site was comprised of 8 residues (DKEDRNEN). However, aspartate and glutamate significantly contributed in the stability of ligand binding. Computational findings were further verified via significant growth inhibition of Aspergillus flavus, A. niger, and Fusarium oxysporum against PsV. Additionally, the substantial adult population of Brevicoryne brassicae was reduced and different life stages of Tribolium castaneum also showed significant mortality.

Comprehensive Structural and Functional Characterization of a Seed γ-thionin as a Potent Bioactive Molecule Against Fungal Pathogens and Insect Pests.

BACKGROUND: Fungi and insect pests ruin stored crop grain, which results in millions of dollars of damage, presenting an ongoing challenge for farmers in addition to diminishing the safety of stored food. A wide-range defensive system against pathogens is needed to reduce or even eliminate the dependence of the crop yield upon the use of pesticides. Plant defensins (γ-thionins) are antimicrobial peptides (AMPs) that are a component of the host defense system. They are known to interact with cell membranes to exhibit antifungal and insecticidal activity. They exhibit a broad range of activities against fungi and insects and are effective at low concentrations. Thionins act on membranes, greatly reducing the development of pathogen resistance. OBJECTIVE: The aim of this study is to investigate a bioactive molecule that acts against fungal pathogens and stored grain insect pests. METHODS: γ-thionin protein was extracted from Brassica oleracea L. var. capitata f. alba (white cabbage) seed powder in phosphate buffer (100 mM, pH 7.0) and was identified by MALDI-TOF/TOF. The crude extract was subjected to 70% ammonium sulfate saturation followed by gel filtration chromatography. The disc diffusion assay along with a microtiter bioassay was used to determine the antifungal activity of the protein against phytopathogenic fungi. The insecticidal efficacy was evaluated by feeding insect pests with food contaminated with the purified protein. Additionally, an in silico molecular structure prediction study of the protein was performed using Auto Dock Vina for molecular docking of the protein with either fungal membrane moieties or α-amylase from Tenebrio molitor L. MD simulations of protein-ligand complexes were conducted using Schrodinger's Desmond module. RESULTS: γ-Thionin (BoT) was purified from white cabbage seeds and showed 100% homology with thionin (Brassica oleracea L. var. viridis) and 80% homology with defensin-like protein 1 (Raphanus sativus L.), respectively. BoT significantly inhibited the mycelial growth of Aspergillus niger van Tieghem and Aspergillus flavus Link at a concentration of 2 µM. Similarly, 0.12 µM BoT treatment resulted in significant mortality of Tribolium castaneum Herbst and Sitophilus oryzae L. Molecular docking and MD simulation of BoT confirmed the strong binding affinity with fungal membrane moieties (phosphatidylinositol 4,5-bisphosphate and phosphatidic acid), which causes disruption of the cell membrane and leakage of the cellular contents, leading to cell death. BoT blocked the active site of α-amylase, and as a result of the inactivation of this gut enzyme, the digestive systems of insects were disturbed, resulting in their deaths. CONCLUSION: This study revealed that γ-thionin is a good antifungal and insecticidal agent that could be used as an alternate to fungicides and insecticides.

Assessing the Empirical Linkage Among Access to Finance, Firm Quality, and Firm Performance: New Insight From Bangladeshi SMEs'.

Access to finance plays a central pillar on the sustainable firm growth of developing and developed nations. This study depicts the linkage between access to external finance, firm quality, and firms' performance as measured by labor productivity for sustainable small- and medium-sized enterprises (SMEs') development by employing the ordinary least squares (OLS) regression and propensity score matching (PSM) techniques to alleviate the selection bias and endogeneity issue on Word bank enterprise survey (WBES) cross-sectional firm-level data of 3,196 Bangladeshi SMEs for 2007-2013 period. Empirical evidence linking access to external finance and labor productivity has been positive and significant. However, our finding explores a negative but significant relationship between exports and SME labor productivity. A further look into the results also exhibits no statistical significance in the interaction effect between firm quality and access to finance on labor productivity. Moreover, the study anticipates novel empirical support that, the disintegration effect of export sales between direct and indirect exports with labor productivity for credit-accessed firms, is also found statistically insignificant. Then, several policies are drawn from the results to gain international competitiveness, and to ensure more external finance channels for enhancing SMEs' performance and sustainable firm growth.

Anakinra treatment efficacy in reduction of inflammatory biomarkers in COVID-19 patients: A meta-analysis.

INTRODUCTION: Anakinra is being empirically considered for the treatment of COVID-19 patients. The aim is to assess the efficacy of anakinra treatment on inflammatory marker reduction, including c-reactive protein (CRP) concentrations, serum ferritin, and serum d-dimer levels. METHODS: Adhering to PRISMA 2020 statement guidelines, a systematic search was conducted across the following databases from December 2019 until January 10, 2022: PubMed/MEDLINE, Cochrane Central, Web of Science, Scopus, and EMBASE. The following keywords were employed: Anakinra, COVID*, SARS-CoV-2, inflammatory, CRP, D-dimer, Ferritin, hematological, laboratory, clinical, trials. The findings were collated and presented in a tabulated manner, and statistically analyzed using Review Manger 5.4 (Cochrane). RESULTS: In total, 2032 patients were included (881 in the anakinra and 1151 in the control/standard care group); 69.1% of them were males. Overall, the mean difference from admission until last follow-up in CRP values was -9.66, where notable reductions were seen in the anakinra group (SMD = -0.46, p < 0.00001, N = 655). Serum ferritin mean values were reduced by 1467.16 in the anakinra group (SMD = -0.31, p = 0.004, N = 537). D-dimer mean values were largely reduced by 4.04 in the anakinra group (SMD = -0.38, p = 0.0004, N = 375). CONCLUSION: This study finds that anakinra is potentially a strong candidate as an anti-inflammatory agent to reduce mortality in COVID-19 patients, specifically in patients with elevated inflammatory biomarkers.