BC-QNet: A quantum-infused ELM model for breast cancer diagnosis.

The timely and accurate diagnosis of breast cancer is pivotal for effective treatment, but current automated mammography classification methods have their constraints. In this study, we introduce an innovative hybrid model that marries the power of the Extreme Learning Machine (ELM) with FuNet transfer learning, harnessing the potential of the MIAS dataset. This novel approach leverages an Enhanced Quantum-Genetic Binary Grey Wolf Optimizer (Q-GBGWO) within the ELM framework, elevating its performance. Our contributions are twofold: firstly, we employ a feature fusion strategy to optimize feature extraction, significantly enhancing breast cancer classification accuracy. The proposed methodological motivation stems from optimizing feature extraction for improved breast cancer classification accuracy. The Q-GBGWO optimizes ELM parameters, demonstrating its efficacy within the ELM classifier. This innovation marks a considerable advancement beyond traditional methods. Through comparative evaluations against various optimization techniques, the exceptional performance of our Q-GBGWO-ELM model becomes evident. The classification accuracy of the model is exceptionally high, with rates of 96.54 % for Normal, 97.24 % for Benign, and 98.01 % for Malignant classes. Additionally, the model demonstrates a high sensitivity with rates of 96.02 % for Normal, 96.54 % for Benign, and 97.75 % for Malignant classes, and it exhibits impressive specificity with rates of 96.69 % for Normal, 97.38 % for Benign, and 98.16 % for Malignant classes. These metrics are reflected in its ability to classify three different types of breast cancer accurately. Our approach highlights the innovative integration of image data, deep feature extraction, and optimized ELM classification, marking a transformative step in advancing early breast cancer detection and enhancing patient outcomes.

Composite Aerogel Scaffolds Containing Flexible Silica Nanofiber and Tricalcium Phosphate Enable Skin Regeneration.

Poor hemostatic ability and less vascularization at the injury site could hinder wound healing as well as adversely affect the quality of life (QOL). An ideal wound dressing should exhibit certain characteristics: (a) good hemostatic ability, (b) rapid wound healing, and (c) skin appendage formation. This necessitates the advent of innovative dressings to facilitate skin regeneration. Therapeutic ions, such as silicon ions (Si4+) and calcium ions (Ca2+), have been shown to assist in wound repair. The Si4+ released from silica (SiO2) can upregulate the expression of proteins, including the vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (α-SMA), which is conducive to vascularization; Ca2+ released from tricalcium phosphate (TCP) can promote the coagulation alongside upregulating the expression of cell migration and cell differentiation related proteins, thereby facilitating the wound repair. The overarching objective of this study was to exploit short SiO2 nanofibers along with the TCP to prepare TCPx@SSF aerogels and assess their wound healing ability. Short SiO2 nanofibers were prepared by electrospinning and blended with varying proportions of TCP to afford TCPx@SSF aerogel scaffolds. The TCPx@SSF aerogels exhibited good cytocompatibility in a subcutaneous implantation model and manifested a rapid hemostatic effect (hemostatic time 75 s) in a liver trauma model in the rabbit. These aerogel scaffolds also promoted skin regeneration and exhibited rapid wound closure, epithelial tissue regeneration, and collagen deposition. Taken together, TCPx@SSF aerogels may be valuable for wound healing.

Exploring the mechanism of action of spirooxindoles as a class of CDK2 inhibitors: a structure-based computational approach.

Cyclin-dependent kinase 2 (CDK2) regulates cell cycle checkpoints in the synthesis and mitosis phases and plays a pivotal role in cancerous cell proliferation. The activation of CDK2, influenced by various protein signaling pathways, initiates the phosphorylation process. Due to its crucial role in carcinogenesis, CDK2 is a druggable hotspot target to suppress cancer cell proliferation. In this context, several studies have identified spirooxindoles as an effective class of CDK2 inhibitors. In the present study, three spirooxindoles (SOI1, SOI2, and SOI3) were studied to understand their inhibitory mechanism against CDK2 through a structure-based approach. Molecular docking and molecular dynamics (MD) simulations were performed to explore their interactions with CDK2 at the molecular level. The calculated binding free energy for the spirooxindole-based CDK2 inhibitors aligned well with experimental results regarding CDK2 inhibition. Energy decomposition (ED) analysis identified key binding residues, including I10, G11, T14, R36, F82, K89, L134, P155, T158, Y159, and T160, in the CDK2 active site and T-loop phosphorylation. Molecular mechanics (MM) energy was identified as the primary contributor to stabilizing inhibitor binding in the CDK2 protein structure. Furthermore, the analysis of binding affinity revealed that the inhibitor SOI1 binds more strongly to CDK2 compared to the other inhibitors under investigation. It demonstrated a robust interaction with the crucial residue T160 in the T-loop phosphorylation site, responsible for kinase activation. These insights into the inhibitory mechanism are anticipated to contribute to the development of potential CDK2 inhibitors using the spirooxindole scaffold.

Genome wide analysis of carotenoid cleavage oxygenases (CCO) gene family in Arachis hypogaea (peanut) under biotic stress.

Carotenoid cleavage oxygenases (CCOs) enzymes play a vital role in plant growth and development through the synthesis of apocarotenoids and their derivative. These chemicals are necessary for flower and fruit coloration, as well as the manufacture of plant hormones such as abscisic acid (ABA) and strigolactones, which control a variety of physiological processes. The CCOs gene family has not been characterized in Arachis hypogaea. Genome mining of A. hypogaea identifies 24 AhCCO gene members. The AhCCO gene family was divided into two subgroups based on the recent study of the Arabidopsis thaliana CCO gene family classification system. Twenty-three AhCCO genes, constituting 95.8% of the total, were regulated by 29 miRNAs, underscoring the significance of microRNAs (miRNAs) in governing gene expression in peanuts. AhCCD19 is the only gene that lacks a miRNA target site. The physicochemical characteristics of CCO genes and their molecular weights and isoelectric points were studied further. The genes were then characterized regarding chromosomal distribution, structure, and promoter cis-elements. Light, stress development, drought stress, and hormone responsiveness were discovered to be associated with AhCCO genes, which can be utilized in developing more resilient crops. The investigation also showed the cellular location of the encoded proteins and discovered that the peanut carotenoid oxygenase gene family's expansion was most likely the result of tandem, segmental, and whole-genome duplication events. The localization expresses the abundance of genes mostly in the cytoplasm and chloroplast. Expression analysis shows that AhCCD7 and AhCCD14 genes show the maximum expression in the apical meristem, lateral leaf, and pentafoliate leaf development, while AhNCED9 and AhNCED13 express in response to Aspergillus flavus resistance. This knowledge throws light on the evolutionary history of the AhCCO gene family and may help researchers better understand the molecular processes behind gene duplication occurrences in plants. An integrated synteny study was used to find orthologous carotenoid oxygenase genes in A. hypogaea, whereas Arabidopsis thaliana and Beta vulgaris were used as references for the functional characterization of peanut CCO genes. These studies provide a foundation for future research on the regulation and functions of this gene family. This information provides valuable insights into the genetic regulation of AhCCO genes. This technology could create molecular markers for breeding programs to develop new peanut lines.

Coupling of phycoremediation and phytoremediation technologies to treat tannery effluents with rainwater dilutions.

From tannery effluent (TE) severely polluted with heavy metals (HMs viz., Cr, Cu, Cd, and Pb), hydrophytic phytoextraction remains a challenge as transplanted plants succumb to death on facing acclimatization shock. Current study was aimed at diluting TE with harvested rainwater (HR) for improving HM phytoextraction potential of Phragmites australis (a hydrophyte) assisted with phycoremediation of coupled algae (viz., Oedogonium sp. and Pithophora sp.). The TE:HR dilutions (TEDs) 0, 25, 50, 75, and 100% (v/v) included three sets: set-1 included algae only, set-2 included P. australis only and set-3 included P. australis coupled with combined algal inoculum. Results showed that P. australis assisted with HR dilution and combined algal inoculum showed significantly greater uptake of HMs from each of the TEDs than respective control treatments. Combined algal application in the TEDs proved phycoremediation assistants based on their bioaccumulation factor (BF). The dry biomass of P. australis in TEDs applied with phycoremediation assistants remained greater than uninoculated ones. Overall, HM translocation factor (TF) of P. australis for Cr, Cu, Cd, and Pb remained ≥ 1. The study concludes that HM phytoextraction is substantially increased when concentrated TE is diluted with HR and assisted with phycoremediation of HM tolerant algae.

Evaluating the Effectiveness and Safety of Evinacumab in Treating Hypercholesterolemia and Hypertriglyceridemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Cardiovascular disease remains a significant global health concern, with high low-density lipoprotein cholesterol (LDL-C) levels contributing to an increased risk. Familial hypercholesterolemia (FH) further complicates its management, necessitating additional lipid-lowering therapies. Evinacumab, an angiopoietin-like protein 3 monoclonal antibody, has emerged as a potential treatment, particularly for patients with FH, by effectively reducing LDL-C and triglyceride levels. This meta-analysis aimed to evaluate the efficacy and safety of evinacumab across diverse patient populations. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, relevant randomized controlled trials (RCTs) were systematically retrieved from multiple databases until November 24, 2023. The inclusion criteria were studies comparing evinacumab (at doses of 5 and 15 mg) to placebo, with outcomes focusing on lipid levels and adverse events. Standardized protocols were employed for data extraction and quality assessment, and statistical analysis was conducted using RevMan software. RESULTS: Four RCTs, involving 270 patients, were included in the analysis. The analysis revealed significant reductions in lipid markers, particularly with the 15-mg dose of evinacumab, including triacylglycerols (standard mean difference [SMD] = -6.09, 95% confidence interval [CI] - 14.53 to 2.36, P = 0.16), total cholesterol (SMD = - 6.20, 95% CI - 11.53 to - 0.88, P = 0.02), high-density lipoprotein cholesterol (SMD = - 0.79, 95% CI - 1.27 to - 0.31, P = 0.001), LDL-C (SMD = - 4.58, 95% CI - 9.13 to - 0.03, P = 0.05), apolipoprotein (Apo) B (SMD = - 4.01, 95% CI - 7.53 to - 0.46, P = 0.03), and Apo C3 (SMD = - 7.67, 95% CI - 12.94 to - 2.41, P = 0.004). Adverse event analysis revealed no significant association, indicating good tolerability. CONCLUSION: High-dose evinacumab (15 mg) consistently demonstrated efficacy in reducing cholesterol and other lipid markers, with favorable tolerability. Further research is warranted to comprehensively assess its safety and clinical effectiveness, emphasizing the need for additional data to support its use in managing cardiovascular disease.

The antibiogram of pus cultures in federal tertiary care hospital, Islamabad and its utility in antimicrobial stewardship.

Background and Objectives: Antimicrobial resistance has emerged as a significant global health threat. Infections caused by Multi Drug-Resistant (MDR) bacteria pose formidable challenges in terms of treatment options and patient outcomes. Pus cultures serve as crucial diagnostic tools in identifying the agents responsible for various infections, and their antimicrobial susceptibility patterns which help in establishment of empirical therapy guidelines. This study was conducted to determine the pathogen and its susceptibility pattern from pus cultures and to generate antibiogram in our tertiary care setting. Materials and Methods: It was a cross-sectional study, conducted for a period of six months, from July 2022 to December 2022, in the Pathology Department of Pakistan Institute of Medical Sciences (PIMS). Results: Out of total 2507 samples received, 1242 (49.5%) showed positive culture. Among the 1242 positive samples, 364 were Gram positive cocci (GPCs) and 878 were Gram negative rods (GNRs). Methicillin resistant Staphylococcus aureus (MRSA) was the most common isolate (23%) followed by Klebsiella pneumoniae (22.6%), Pseudomonas aeruginosa (16.9%), Enterobacter spp. (15.5%) and Escherichia coli (14.2%). Vancomycin was found to be highly effective (100%) against MRSA. GPCs were highly susceptible to linezolid (98%) while GNRs showed high level of sensitivity to colistin (96%) and tigecycline (92%). Conclusion: The generation of a local antibiogram specific to the hospital setting is essential to effectively manage infections empirically and preserve the efficacy of existing antibiotics. By implementing antimicrobial stewardship practices based on a better understanding of antibiotic susceptibility patterns, we can contribute to the mitigation of antibiotic resistance and improve patient outcomes.

Genetics aspect of vitamin C (Ascorbic Acid) biosynthesis and signaling pathways in fruits and vegetables crops.

Vitamin C, also known as ascorbic acid, is an essential nutrient that plays a critical role in many physiological processes in plants and animals. In humans, vitamin C is an antioxidant, reducing agent, and cofactor in diverse chemical processes. The established role of vitamin C as an antioxidant in plants is well recognized. It neutralizes reactive oxygen species (ROS) that can cause damage to cells. Also, it plays an important role in recycling other antioxidants, such as vitamin E, which helps maintain the overall balance of the plant's antioxidant system. However, unlike plants, humans cannot synthesize ascorbic acid or vitamin C in their bodies due to the absence of an enzyme called gulonolactone oxidase. This is why humans need to obtain vitamin C through their diet. Different fruits and vegetables contain varying levels of vitamin C. The biosynthesis of vitamin C in plants occurs primarily in the chloroplasts and the endoplasmic reticulum (ER). The biosynthesis of vitamin C is a complex process regulated by various factors such as light, temperature, and plant hormones. Recent research has identified several key genes that regulate vitamin C biosynthesis, including the GLDH and GLDH genes. The expression of these genes is known to be regulated by various factors such as light, temperature, and plant hormones. Recent studies highlight vitamin C's crucial role in regulating plant stress response pathways, encompassing drought, high salinity, and oxidative stress. The key enzymes in vitamin C biosynthesis are L-galactose dehydrogenase (GLDH) and L-galactono-1, 4-lactone dehydrogenase (GLDH). Genetic studies reveal key genes like GLDH and GLDH in Vitamin C biosynthesis, offering potential for crop improvement. Genetic variations influence nutritional content through their impact on vitamin C levels. Investigating the roles of genes in stress responses provides insights for developing resilient techniques in crop growth. Some fruits and vegetables, such as oranges, lemons, and grapefruits, along with strawberries and kiwi, are rich in vitamin C. Guava. Papaya provides a boost of vitamin C and dietary fiber. At the same time, red and yellow bell peppers, broccoli, pineapple, mangoes, and kale are additional sources of this essential nutrient, promoting overall health. In this review, we will discuss a brief history of Vitamin C and its signaling and biosynthesis pathway and summarize the regulation of its content in various fruits and vegetables.

Genome-wide analysis of NPR1-like genes in citrus species and expression analysis in response to citrus canker (Xanthomonas axonopodis pv. citri).

Citrus fruits, revered for their nutritional value, face significant threats from diseases like citrus canker, particularly impacting global citrus cultivation, notably in Pakistan. This study delves into the critical role of NPR1-like genes, the true receptors for salicylic acid (SA), in the defense mechanisms of citrus against Xanthomonas axonopodis pv. citri (Xcc). By conducting a comprehensive genome-wide analysis and phylogenetic study, the evolutionary dynamics of Citrus limon genes across diverse citrus cultivars are elucidated. Structural predictions unveil conserved domains, such as the BTB domain and ankyrin repeat domains, crucial for the defense mechanism. Motif analysis reveals essential conserved patterns, while cis-regulatory elements indicate their involvement in transcription, growth, response to phytohormones, and stress. The predominantly cytoplasmic and nuclear localization of NPR1-like genes underscores their pivotal role in conferring resistance to various citrus species. Analysis of the Ks/Ka ratio indicates a purifying selection of NPR1-like genes, emphasizing their importance in different species. Synteny and chromosomal mapping provide insights into duplication events and orthologous links among citrus species. Notably, Xac infection stimulates the expression of NPR1-like genes, revealing their responsiveness to pathogenic challenges. Interestingly, qRT-PCR profiling post-Xac infection reveals cultivar-specific alterations in expression within susceptible and resistant citrus varieties. Beyond genetic factors, physiological parameters like peroxidase, total soluble protein, and secondary metabolites respond to SA-dependent PR genes, influencing plant characteristics. Examining the impact of defense genes (NPR1) and plant characteristics on disease resistance in citrus, this study marks the inaugural investigation into the correlation between NPR1-associated genes and various plant traits in both susceptible and resistant citrus varieties to citrus bacterial canker.

Biosynthesized metallic nanoparticles: A new era in cancer therapy.

Cancer remains a global health crisis, claiming countless lives throughout the years. Traditional cancer treatments like chemotherapy and radiation often bring about severe side effects, underscoring the pressing need for innovative, more efficient, and less toxic therapies. Nanotechnology has emerged as a promising technology capable of producing environmentally friendly anticancer nanoparticles. Among various nanoparticle types, metal-based nanoparticles stand out due to their exceptional performance and ease of use in methods of imaging. The widespread accessibility of biological precursors for synthesis based on plants of metal nanoparticles has made large-scale, eco-friendly production feasible. This evaluation provides a summary of the green strategy for synthesizing metal-based nanoparticles and explores their applications. Moreover, this review delves into the potential of phyto-based metal nanoparticles in combating cancer, shedding light on their probable mechanisms of action. These insights are invaluable for enhancing both biomedical and environmental applications. The study also touches on the numerous potential applications of nanotechnology in the field of medicine. Consequently, this research offers a concise and well-structured summary of nanotechnology, which should prove beneficial to researchers, engineers, and scientists embarking on future research endeavors.

Genome-wide identification and in-silico expression analysis of CCO gene family in sunflower (Helianthus annnus) against abiotic stress.

Carotenoid cleavage oxygenases (CCOs) enzymes play an important role in plant growth and development by producing a wide array of apocarotenoids and their derivatives. These compounds are vital for colouring flowers and fruits and synthesizing plant hormones such as abscisic acid and strigolactones. Despite their importance, the gene family responsible for CCO enzymes in sunflowers has not been identified. In this study, we identify the CCO genes of the sunflower plant to fill this knowledge gap. Phylogenetic and synteny analysis indicated that the Helianthus annnus CCO (HaCCO) genes were conserved in different plant species and they could be divided into three subgroups based on their conserved domains. Analysis using MEME tool and multiple sequence alignment identified conserved motifs in the HaCCO gene sequence. Cis-regulatory elements (CREs) analysis of the HaCCO genes indicated the presence of various responsive elements related to plant hormones, development, and responses to both biotic and abiotic stresses. This implies that these genes may respond to plant hormones, developmental cues, and drought stress, offering potential applications in the development of more resistant crops. Genes belonging to the 9-cis-epoxy carotenoid dioxygenases (NCED) subgroups predominantly exhibited chloroplast localization, whereas the genes found in other groups are primarily localized in the cytoplasm. These 21 identified HaCCOs were regulated by 60 miRNAs, indicating the crucial role of microRNAs in gene regulation in sunflowers. Gene expression analysis under drought stress revealed significant up-regulation of HaNCED16 and HaNCED19, genes that are pivotal in ABA hormone biosynthesis. During organ-specific gene expression analysis, HaCCD12 and HaCCD20 genes exhibit higher activity in leaves, indicating a potential role in leaf pigmentation. This study provides a foundation for future research on the regulation and functions of the CCO gene family in sunflower and beyond. There is potential for developing molecular markers that could be employed in breeding programs to create new sunflower lines resistant to biotic and abiotic stresses.

Real-time navigation of mecanum wheel-based mobile robot in a dynamic environment.

Path planning and control of a mobile robot, in a dynamic environment, has been an important research topic for many years. In this paper an algorithm for autonomous motion of a mobile robot is proposed, with mecanum wheels, to reach a goal while avoiding obstacles through the shortest path in a dynamic environment. The proposed method uses a hybrid A⁎ and a velocity obstacle algorithms for path planning and obstacle avoidance. The A⁎ algorithm is implemented to explore the shortest path from starting position to the goal while avoiding all the static obstacles. However, in real time applications the dynamic obstacles need to be avoided, therefore, for such a case velocity obstacle algorithm is unified with the A⁎ algorithm. Initially, the proposed algorithm is verified through simulations. Then it is implemented using experimental setup in real time environment using single and multiple static obstacles as well as on a dynamic obstacle. It can be observed that the robot reaches the goal, effectively by avoiding static and dynamic obstacles. Moreover, the performance of the proposed work is evaluated through qualitative comparison between proposed method and recently published work, showing that the proposed algorithm is gives better features than existing work. In the end, the possible application of mobile robot having mecanum wheels with proposed path planning method is also given in the paper.

Methacrylated gelatin and platelet-rich plasma based hydrogels promote regeneration of critical-sized bone defects.

Physiological repair of large-sized bone defects requires instructive scaffolds with appropriate mechanical properties, biocompatibility, biodegradability, vasculogenic ability and osteo-inductivity. The objective of this study was to fabricate in situ injectable hydrogels using platelet-rich plasma (PRP)-loaded gelatin methacrylate (GM) and employ them for the regeneration of large-sized bone defects. We performed various biological assays as well as assessed the mechanical properties of GM@PRP hydrogels alongside evaluating the release kinetics of growth factors (GFs) from hydrogels. The GM@PRP hydrogels manifested sufficient mechanical properties to support the filling of the tissue defects. For biofunction assay, the GM@PRP hydrogels significantly improved cell migration and angiogenesis. Especially, transcriptome RNA sequencing of human umbilical vein endothelial cells and bone marrow-derived stem cells were performed to delineate vascularization and biomineralization abilities of GM@PRP hydrogels. The GM@PRP hydrogels were subcutaneously implanted in rats for up to 4 weeks for preliminary biocompatibility followed by their transplantation into a tibial defect model for up to 8 weeks in rats. Tibial defects treated with GM@PRP hydrogels manifested significant bone regeneration as well as angiogenesis, biomineralization, and collagen deposition. Based on the biocompatibility and biological function of GM@PRP hydrogels, a new strategy is provided for the regenerative repair of large-size bone defects.

Genome-wide analysis of plant specific YABBY transcription factor gene family in carrot (Dacus carota) and its comparison with Arabidopsis.

YABBY gene family is a plant-specific transcription factor with DNA binding domain involved in various functions i.e. regulation of style, length of flowers, and polarity development of lateral organs in flowering plants. Computational methods were utilized to identify members of the YABBY gene family, with Carrot (Daucus carota) 's genome as a foundational reference. The structure of genes, location of the chromosomes, protein motifs and phylogenetic investigation, syntony and transcriptomic analysis, and miRNA targets were analyzed to unmask the hidden structural and functional characteristics YABBY gene family in Carrots. In the following research, it has been concluded that 11 specific YABBY genes irregularly dispersed on all 9 chromosomes and proteins assembled into five subgroups i.e. AtINO, AtCRC, AtYAB5, AtAFO, and AtYAB2, which were created on the well-known classification of Arabidopsis. The wide ranges of YABBY genes in carrots were dispersed due to segmental duplication, which was detected as prevalent when equated to tandem duplication. Transcriptomic analysis showed that one of the DcYABBY genes was highly expressed during anthocyanin pigmentation in carrot taproots. The cis-regulatory elements (CREs) analysis unveiled elements that particularly respond to light, cell cycle regulation, drought induce ability, ABA hormone, seed, and meristem expression. Furthermore, a relative study among Carrot and Arabidopsis genes of the YABBY family indicated 5 sub-families sharing common characteristics. The comprehensive evaluation of YABBY genes in the genome provides a direction for the cloning and understanding of their functional properties in carrots. Our investigations revealed genome-wide distribution and role of YABBY genes in the carrots with best-fit comparison to Arabidopsis thaliana.

Assessing the efficacy of cinnamon compounds against H. pylori through molecular docking, MD Simulations and ADMET analyses.

Antibiotics are the drugs that are used for the management of microbial diseases. However, these conventional synthetic drugs can harmfully affect the human health. Since phytochemicals are extracted from natural sources and, are hence relatively safer for human health, they are the enticing alternatives in this regard. Cinnamon is also one of those plants which is being employed as herbal medication for centuries against certain microbial infections due its significant therapeutic effectiveness. A well-known pathogenic bacterium called H. pylori causes a wide range of illnesses in human body. This pathogen's pathogenicity is determined by certain virulent proteins. In this study, some of such proteins, which included virB4, virB8, and virB9 were selected to evaluate the therapeutic efficiency of cinnamon compounds. These proteins were identified in different isolates of H. pylori. The structural modelling of all these proteins were performed initially in order to proceed them for molecular docking analysis. While, the docking studies illustrated that one of the cinnamon compounds, cinnamyl acetate, showed significant binding interactions with virB4 and virB9. However, benzyl benzoate which is another cinnamon compound, docked well with virB8. Afterwards, the MD simulations were incorporated to explore the interaction motions and structural stability of all the docked complexes. In this regard, the resultant maps of Bfactor, eigenvalues and elastic network model, among other factors ensured the structural stabilities of all the respective complexes. After these crucial estimations, benzyl benzoate and cinnamyl acetate underwent the ADMET investigation to assess their pharmacokinetic characteristics. SwissADME and ADMETLab 2.0 server were employed for this investigation. The compiled findings these servers revealed that both, benzyl benzoate and cinnamyl acetate, exhibited a significant level of pharmacokinetic and drug-likeness conformity.

Variability in Reproductive Choices: A Comprehensive Analysis of Women's Working Status and Fertility Behavior in Pakistan.

The relationship between women's working status and fertility behavior has been a topic of interest for researchers and policymakers. The societal shifts over time, particularly the increasing participation of women in the workforce, have transformed traditional roles. Women, once primarily perceived as caregivers, are now assuming roles of economic independence. This transformation prompts a re-evaluation of the traditional association between women's working status and fertility behavior. This study aims to investigate the impact of women's working status on fertility behavior using a multistage stratified sampling design. A total of 408 women aged 15 to 49 years were recruited from 2 strata: working and non-working women. The data were collected through face-to-face interviews using a structured questionnaire. Descriptive statistics, cluster analysis, and generalized additive models were used for in-depth analysis of the dataset. An examination of fertility patterns indicates that, on average, working women bear 2.90 live children, while their non-working counterparts have an average of 3.52 children. Stillbirth was reported in 13% of housewives and 15.1% of working women. However, further analysis revealed that the relationship between women's employment status and fertility behavior varied depending on Social and Cultural Norms, Reproductive Rights, Workplace Policies, Economic Independence, Age, and Life Stage. Our findings suggest that promoting access to family-friendly policies and services, as well as challenging gender norms and cultural values, could help address the impact of women's employment on fertility behavior.

Evaluation of chalcones as new glycogen phosphorylase inhibitors - an in-vitro and in-silico approach.

Diabetes mellitus (DM) remains one of the pivotal diseases that have drawn the attention of researchers recently and during the last few decades. Due to its devastating symptoms, attempts to develop new drugs with mild side effects have resulted in a number of drugs that are functioning through various mechanisms. Among these, Glycogen phosphorylase (GP) inhibitors emerged as a new strategy for combating DM. GP is an enzyme that regulates blood glucose levels; it catalyses the breakdown of glycogen to glucose-1-phosphate in the liver and tissues with high and fluctuating energy demands. In the present research, we evaluate the possibility of type 2 diabetes therapy with the help of chalcones which are known to have antidiabetic activities. For this purpose, 29 chalcones were modelled, synthesised and investigated for their inhibitory activity against GP using in-vitro methods. Compounds 1, 2, and 3 were found to be the most potent compounds with IC50 values 26.6, 57.1 and 75.6 µM respectively. The observed results were further validated using in-silico methods. Molecular docking simulation revealed interaction patterns that explain the structure-activity relationships of the compounds with GP. Molecular dynamic (MD) simulation demonstrated a stable complex formation between compound 1 and GP through lower value and uniformity in root mean square deviation (RMSD) of the complex and root mean square fluctuation (RMSF) of the protein Cα.

A deep learning-based theoretical protocol to identify potentially isoform-selective PI3Kα inhibitors.

Phosphoinositide 3-kinase alpha (PI3Kα) is one of the most frequently dysregulated kinases known for their pivotal role in many oncogenic diseases. While the side effects linked to existing drugs against PI3Kα-induced cancers provide an avenue for further research, the significant structural conservation among PI3Ks makes it extremely difficult to develop new isoform-selective PI3Kα inhibitors. Embracing this challenge, we herein designed a hybrid protocol by integrating machine learning (ML) with in silico drug-designing strategies. A deep learning classification model was developed and trained on the physicochemical descriptors data of known PI3Kα inhibitors and used as a screening filter for a database of small molecules. This approach led us to the prediction of 662 compounds showcasing appropriate features to be considered as PI3Kα inhibitors. Subsequently, a multiphase molecular docking was applied to further characterize the predicted hits in terms of their binding affinities and binding modes in the targeted cavity of the PI3Kα. As a result, a total of 12 compounds were identified whereas the best poses highlighted the efficiency of these ligands in maintaining interactions with the crucial residues of the protein to be targeted for the inhibition of associated activity. Notably, potential activity of compound 12 in counteracting PI3Kα function was found in a previous in vitro study. Following the drug-likeness and pharmacokinetic characterizations, six compounds (compounds 1, 2, 3, 6, 7, and 11) with suitable ADME-T profiles and promising bioavailability were selected. The mechanistic studies in dynamic mode further endorsed the potential of identified hits in blocking the ATP-binding site of the receptor with higher binding affinities than the native inhibitor, alpelisib (BYL-719), particularly the compounds 1, 2, and 11. These outcomes support the reliability of the developed classification model and the devised computational strategy for identifying new isoform-selective drug candidates for PI3Kα inhibition.