National income accounting attributes and economic welfare. Evidence from Pakistan.

Economic welfare is essential in the modern economy since it directly reflects the standard of living, distribution of resources, and general social satisfaction, which influences individual and social well-being. This study aims to explore the relationship between national income accounting different attributes and the economic welfare in Pakistan. However, this study used data from 1950 to 2022, and data was downloaded from the World Bank data portal. Regression analysis is used to investigate the relationship between them and is very effective in measuring the relationship between endogenous and exogenous variables. Moreover, generalized methods of movement (GMM) are used as the robustness of the regression. Our results show that foreign direct investment outflow, Gross domestic product growth rate, GDP per capita, higher Interest, market capitalization, and population growth have a significant negative on the unemployment rate, indicating the rise in these factors leads to a decrease in the employment rate in Pakistan. Trade and savings have a significant positive impact on the unemployment rate, indicating the rise in these factors leads to an increase in the unemployment rate for various reasons. Moreover, all the factors of national income accounting have a significant positive relationship with life expectancy, indicating that an increase in these factors leads to an increase in economic welfare and life expectancy due to better health facilities, many resources, and correct economic policies. However, foreign direct investment, inflation rate, lending interest rate, and population growth have significant positive effects on age dependency, indicating these factors increase the age dependency. Moreover, GDP growth and GDP per capita negatively impact age dependency. Similarly, all the national income accounting factors have a significant negative relationship with legal rights that leads to decreased legal rights. Moreover, due to better health facilities and health planning, there is a negative significant relationship between national income accounting attributes and motility rate among children. Our study advocated the implications for the policymakers and the government to make policies for the welfare and increase the social factors.

Development of hybrid polyvinylpyrrolidone/carboxymethyl cellulose/collagen incorporated oregano scaffolds via direct ink write printing for potential wound healing applications.

Additive manufacturing can develop regenerative scaffolds for wound healing. 3D printing offers meticulous porosity, mechanical integrity, cell adhesion and cost-effectiveness. Herein, we prepared ink composed of carboxymethyl cellulose (CMC), polyvinylpyrrolidone (PVP), collagen, and oregano extract for the fabrication of tissue constructs. The blend was optimized to form a homogeneous ink and rheological characterization demonstrated shear thinning behavior. The scaffolds were printed using Direct Ink Write (DIW) at a flow speed of 4 mm3/s and a layer height of 0.18 mm. The fabricated scaffolds demonstrated an ultimate tensile strength (UTS) and toughness of 730 KPa and 2.72 MJ/m3, respectively. Scanning Electron Microscopy (SEM) revealed an average pore size of 300 ±â€¯30 µm. Fourier transform infrared spectroscopy (FTIR) analysis confirmed that all materials were present. The contact angle of the composite scaffold was 68o ±â€¯1o. Moreover, the scaffolds presented 82 % mass loss (degradation) in phosphate buffer saline (PBS) over 14 days. The composite scaffold exhibited inhibition zones of 9 mm and 12 mm against Staphylococcus aureus and Escherichia coli, respectively. The PVP/CMC/collagen/oregano 3D printed scaffolds exhibited excellent biocompatibility with the mesenchymal stem cells confirmed by water-soluble tetrazolium - 8 (WST-8) ass (test conducted for 7 days). Thus, confirming suitability for the potential wound healing application.

Embracing the sustainable horizons through bioenergy innovations: a path to a sustainable energy future.

The urgent need for mitigating climate change necessitates a transformative shift in energy production and consumption paradigms. Amidst this challenge, bioenergy emerges as a pivotal contributor to the global energy transition, offering a diverse array of solid, liquid, and gaseous fuels derived from biomass. This mini review delves into the unique potential of bioenergy innovations, particularly renewable diesel, bio jet fuel, and ethanol, to reduce greenhouse gas emissions and transform various industries. The article highlights critical technological advancements, supportive policies, and cross-sector collaboration essential for a sustainable energy transition. Specific challenges such as ensuring a consistent biomass feedstock supply, decentralizing processing units, and navigating complex regulatory frameworks are examined. Innovative solutions like decentralized biomass processing and enhanced biomass logistics are discussed as pathways to overcome these barriers. The review provides specific recommendations for near-term policies and strategies to support decentralized facilities, showcasing bioenergy's role in achieving a sustainable future.

Genomic Insights into and In Vitro Evaluation of Antimicrobial Combination Therapies for Carbapenem-Resistant Acinetobacter baumannii.

Background and Objectives: Acinetobacter baumannii (A. baumannii), particularly carbapenem-resistant A. baumannii (CRAB), represents a grave concern in healthcare settings and is associated with high mortality. This study aimed to conduct molecular, mutational, and phylogenetic analyses of specific genes in CRAB and evaluate the synergistic effects of selected antimicrobial combinations. Materials and Methods: Phenotypic characterization was performed on six CRAB strains by using the Modified Hodge Test (MHT) and IMP-EDTA Double-Disc Synergy Test (IMP-EDTA DDST). Carbapenemase- and metallo-beta-lactamase-encoding genes were amplified by using Polymerase Chain Reaction. Phylogenetic analysis using the MEGA 11 tool was used to determine the evolutionary relatedness of these genes. Mutational analysis was performed by using I-Mutant, MUPro, and PHD-SNP bioinformatics tools to predict mutations in the carbapenemase-encoding genes. Microdilution checkerboard titration assessed the synergistic effects of antimicrobial combinations (azithromycin-meropenem, rifampicin-meropenem, meropenem-colistin, and azithromycin-colistin) on these CRAB isolates. Results: The phenotypic characterization of six CRAB isolates revealed positive results for MHT and IMP-EDTA DDST. The molecular characterization revealed that carbapenemase- and MBL-encoding genes were present in all isolates with varying frequencies, including blaOXA-51 (100%) and blaIMP (0%). The sequence analysis revealed high evolutionary relatedness to sequences in the NCBI database. The mutational analysis identified 16 mutations, of which 1 mutation (P116L) in the blaOXA-58 gene predicted a change in the protein product, potentially contributing to carbapenem resistance. The checkerboard titration method did not reveal any synergism among the tested antimicrobial combinations against CRAB. Conclusion: This study's findings underscore the significant challenges posed by CRAB isolates harboring multiple resistant genes in treatment. This highlights the urgent need for novel antimicrobial agents, a crucial step towards reducing mortality rates not only in Pakistan but also globally.

Multiple cropping effectively increases soil bacterial diversity, community abundance and soil fertility of paddy fields.

BACKGROUND: Crop diversification is considered as an imperative approach for synchronizing the plant nutrient demands and soil nutrient availability. Taking two or more crops from the same field in one year is considered as multiple cropping. It improves the diversity and abundance of soil microbes, thereby improving the growth and yield of crops. Therefore, the present study was conducted to explore the effects of different multiple winter cropping on soil microbial communities in paddy fields. In this study, eight rice cropping patterns from two multiple cropping systems with three different winter crops, including Chinese milk vetch (CMV), rape, and wheat were selected. The effects of different multiple winter cropping on soil microbial abundance, community structure, and diversity in paddy fields were studied by 16 S rRNA high-throughput sequencing and real-time fluorescence quantitative polymerase chain reaction (PCR). RESULTS: The results showed that different multiple winter cropping increased the operational taxonomic units (OTUs), species richness, and community richness index of the bacterial community in 0 ~ 20 cm soil layer. Moreover, soil physical and chemical properties of different multiple cropping patterns also affected the diversity and abundance of microbial bacterial communities. The multiple cropping increased soil potassium and nitrogen content, which significantly affected the diversity and abundance of bacterial communities, and it also increased the overall paddy yield. Moreover, different winter cropping changed the population distribution of microorganisms, and Proteobacteria, Acidobacteria, Nitrospira, and Chloroflexi were identified as the most dominant groups. Multiple winter cropping, especially rape-early rice-late rice (TR) andChinese milk vetch- early rice-late rice (TC) enhanced the abundance of Proteobacteria, Acidobacteria, and Actinobacteria and decreased the relative abundance of Verrucomicrobia and Euryarchaeota. CONCLUSION: In conclusion, winter cropping of Chinese milk vetch and rape were beneficial to improve the soil fertility, bacteria diversity, abundance and rice yield.

Advances in MXene-based technologies for the remediation of toxic phenols: A comprehensive review.

The pressing global issue of organic pollutants, particularly phenolic compounds derived primarily from industrial wastes, poses a significant threat to the environment. Although progress has been made in the development of low-cost materials for phenolic compound removal, their effectiveness remains limited. Thus, there is an urgent need for novel technologies to comprehensively address this issue. In this context, MXenes, known for their exceptional physicochemical properties, have emerged as highly promising candidates for the remediation of phenolic pollutants. This review aims to provide a comprehensive and critical evaluation of MXene-based technologies for the removal of phenolic pollutants, focusing on the following key aspects: (1) The classification and categorization of phenolic pollutants, highlighting their adverse environmental impacts, and emphasizing the crucial need for their removal. (2) An in-depth discussion on the synthesis methods and properties of MXene-based composites, emphasizing their suitability for environmental remediation. (3) A detailed analysis of MXene-based adsorption, catalysis, photocatalysis, and hybrid processes, showcasing current advancements in MXene modification and functionalization to enhance removal efficiency. (4) A thorough examination of the removal mechanisms and stability of MXene-based technologies, elucidating their operating conditions and stability in pollutant removal scenarios. (5) Finally, this review concludes by outlining future challenges and opportunities for MXene-based technologies in water treatment, facilitating their potential applications. This comprehensive review provides valuable insights and innovative ideas for the development of versatile MXene-based technologies tailored to combat water pollution effectively.

Advances in pH Sensing: From Traditional Approaches to Next-Generation Sensors in Biological Contexts.

pH has been considered one of the paramount factors in bodily functions because most cellular tasks exclusively rely on precise pH values. In this context, the current techniques for pH sensing provide us with the futuristic insight to further design therapeutic and diagnostic tools. Thus, pH-sensing (electrochemically and optically) is rapidly evolving toward exciting new applications and expanding researchers' interests in many chemical contexts, especially in biomedical applications. The adaptation of cutting-edge technology is subsequently producing the modest form of these biosensors as wearable devices, which are providing us the opportunity to target the real-time collection of vital parameters, including pH for improved healthcare systems. The motif of this review is to provide insight into trending tech-based systems employed in real-time or in-vivo pH-responsive monitoring. Herein, we briefly go through the pH regulation in the human body to help the beginners and scientific community with quick background knowledge, recent advances in the field, and pH detection in real-time biological applications. In the end, we summarize our review by providing an outlook; challenges that need to be addressed, and prospective integration of various pH in vivo platforms with modern electronics that can open new avenues of cutting-edge techniques for disease diagnostics and prevention.

Excessive Dynamic Airway Collapse After Entecavir Use in a Patient With Pegylated Interferon-Induced Undifferentiated Connective Tissue Disease and Entecavir Use to Prevent Hepatitis B Virus Reactivation Upon Giving Rituximab.

Pegylated interferon-alpha (PEG-IFN-α) is an antiviral medication used to treat chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. It may result in rare but severe side effects, such as undifferentiated connective tissue disease (UCTD) and excessive dynamic airway collapse (EDAC), which can occur as delayed complications of PEG-IFN-α-induced UCTD. In cases where these complications arise, entecavir, employed for treating HBV infection, may be considered. A 49-year-old female patient, monitored for nine years with HCV and a viral load of 1.5 million, genotype 3, and normal liver function tests (LFTs), possibly acquired the infection from her HCV-positive husband. The patient was initially treated with PEG-IFN-α (IFN-α-2b, 100 µg/week subcutaneously) and ribavirin (RBV, 500 mg/twice daily). Following the sixth injection, the patient exhibited symptoms, including shortness of breath and cough, leading to limited daily activities. Subsequent high-resolution computed tomography (HRCT) showed interstitial pneumonitis (IP) signs. She was given a high dose of steroids. Over the next two to four weeks, the patient experienced Raynaud's phenomenon, skin tightening, joint pains, and dryness of the eyes and mouth. The antinuclear antibody (ANA) test was negative, while the extractable nuclear antigen (ENA) test showed equivocal anti-Smith antibodies (6.38). Rheumatoid factor (RA) factors were mildly positive, and pulmonary function tests (PFTs) indicated a restrictive pattern. The patient was intolerant to hydroxychloroquine (HCQ) and azathioprine (Imuran) 500 mg, subsequently receiving mycophenolate mofetil 500 mg/thrice daily. Despite four years of treatment, UCTD due to PEG-IFN-α remained difficult to control; however, IP responded well to steroids. Rituximab pulse therapy was planned before the initiation; serological tests showed positive anti-HBs with a titer of 17.02, positive anti-HBc, but negative HBsAg and undetectable HBV viral load, indicating immunity to HBV due to natural infection. Given the potential for rituximab to cause immunosuppression and HBV reactivation, entecavir treatment was started and continued for 18 months. The patient was followed for another five years, during which her LFTs and viral markers showed stability. However, after nine years of PEG-IFN-α-induced UCTD disorder, she experienced a reoccurring cough but was unresponsive to steroids that were against her suspicion of a flare of IP. A subsequent dynamic CT scan detected a 75% trachea collapse while in a supine position, indicating a potential complication termed EDAC. This EDAC could not be linked to PEG-IFN-α-induced UCTD disorder or EDAC after the use of entecavir in a patient with PEG-IFN-α-induced UCTD disorder. Treatment of such complex patients requires flexible, specific treatment plans and continuous monitoring. This case emphasizes the need for caution in patients with a history of IFN-induced disease and the possibility of late effects and possible effects of the use of entecavir in a patient with PEG-IFN-α-induced UCTD. To the best of our knowledge, this is the first case reported as EDAC, a possible delayed complication of PEG-IFN-α plus ribavirin or entecavir in a patient with PEG-IFN-α-induced UCTD.

Efficient rhodamine B dye photocatalytic degradation in aqueous media using novel ZnO nanomaterials co-doped with Ce and Dy.

Water pollution caused by dyes and industrial wastewater poses a significant threat to ecosystems. The purification of such pollutants presents a major challenge. Photocatalysis based on semiconductor materials is a potential wastewater treatment process due to its safety and cost-effectiveness. In the present work, Zn1-2xCexDyxO (x = 0.01-0.05) semiconductors were prepared by the sol-gel auto-ignition method. The samples are denoted CDZO1, CDZO3, and CDZO5 for x  = 0.01-0.05, respectively. The X-ray diffraction and Raman spectroscopy results revealed the formation of ZnO hexagonal phase wurtzite structure for all synthesized compositions. Different structural properties were determined. It was found that the lattice parameters and the unit cell volume increased, while the crystallite size diminished as x varied from 0.01 to 0.05. Transmission electron microscopy observations confirmed the formation of nanoparticles with the desired chemical compositions. The specific surface area (SSA) values are found to be 39.95 m2/g, 48.62 m2/g, and 51.36 m2/g for CDZO1, CDZO5, and CDZO5 samples, respectively. The reflectance spectra were recorded to examine the optical properties of the different nanoparticles. The values of the optical band gap were 3.221, 3.225, and 3.239 eV for CDZO1, CDZO3, and CDZO5 samples, respectively. In addition, the photocatalytic performance towards RhB dye degradation for the different samples was assessed. It was established that the CDZO3 sample with a moderate SSA value exhibited the superior photocatalytic performance among the other as-prepared samples wherein the percentage of degradation efficiency, and kinetic constant rate attained their maximum values of 98.22 % and 0.0521 min-1, respectively within 75 min. As per the obtained findings, it is evident that the Zn1-2xCexDyxO photocatalyst has prominent potential for use in the degradation of dyes and offers a useful route for impeding the recombination of electron-hole pairs of zinc oxide material.

Effect of boundary slips and magnetohydrodynamics on peristaltic mechanism of Jeffrey nanofluid along with microorganisms through a porous medium.

The development on entropy generation in fluid flows has applications in many medical equipment such as cryogenic devices and therapeutic heat apparatus. This study looks at how porous medium, multi-slips, and entropy formation affect the pumping of Jeffrey nanofluid flow through an asymmetric channel containing motile microorganims. A lubrication theory is used to neglect the fluctuation effects in the flow. Numerical simulations are utilized to generate data for specific physical features of the problem utilizing the Shooting approach on Mathematica. Following a thorough research, it is appropriate to conclude that the porous medium's permeability reduces flow speed along the walls while increases at the center of the flow region. Graphical representation of the results further reveals that entropy production can be decreased by including high thermal slip and low viscous slip elements. It is also worth noting that the Brinkman number reduces the thermal distribution in the flow while it helps in increasing the flow speed.

Putting Biochar in Action: A Black Gold for Efficient Mitigation of Salinity Stress in Plants. Review and Future Directions.

Soil salinization is a serious concern across the globe that is negatively affecting crop productivity. Recently, biochar received attention for mitigating the adverse impacts of salinity. Salinity stress induces osmotic, ionic, and oxidative damages that disturb physiological and biochemical functioning and nutrient and water uptake, leading to a reduction in plant growth and development. Biochar maintains the plant function by increasing nutrient and water uptake and reducing electrolyte leakage and lipid peroxidation. Biochar also protects the photosynthetic apparatus and improves antioxidant activity, gene expression, and synthesis of protein osmolytes and hormones that counter the toxic effect of salinity. Additionally, biochar also improves soil organic matter, microbial and enzymatic activities, and nutrient and water uptake and reduces the accumulation of toxic ions (Na+ and Cl), mitigating the toxic effects of salinity on plants. Thus, it is interesting to understand the role of biochar against salinity, and in the present Review we have discussed the various mechanisms through which biochar can mitigate the adverse impacts of salinity. We have also identified the various research gaps that must be addressed in future study programs. Thus, we believe that this work will provide new suggestions on the use of biochar to mitigate salinity stress.

Fabrication of photo-induced molecular superoxide radical generator for highly efficient therapy against bacterial wound infection.

The pressing need for highly efficient antibacterial strategies arises from the prevalence of microbial biofilm infections and the emergence of rapidly evolving antibiotic-resistant strains of pathogenic bacteria. Photodynamic therapy represents a highly efficient and compelling antibacterial approach, offering promising prospects for effective control of the development of bacterial resistance. However, the effectiveness of many photosensitizers is limited due to the reduced generation of reactive oxygen species (ROS) in hypoxic microenvironment, which commonly occur in pathological conditions such as inflammatory and bacteria-infected wounds. Herein, we designed and prepared two phenothiazine-derived photosensitizers (NB-1 and NB-2), which can effectively generate superoxide anion radicals (O2●-) through the type I process. Both photosensitizers demonstrate significant efficacy in vitro for the eradication of broad-spectrum bacteria. Moreover, NB-2 possesses distinct advantages including strong membrane binding and strong generation of O2●-, rendering it an exceptionally efficient antibacterial agent against mature biofilms. In addition, laser activated NB-2 could be applied to treat MRSA-infected wound in vivo, which offers new opportunities for potential practical applications.

Development and characterization of polyethylene oxide and guar gum-based hydrogel; a detailed in-vitro analysis of degradation and drug release kinetics.

Herein, we synthesized hydrogel films from crosslinked polyethylene oxide (PEO) and guar gum (GG) which can offer hydrophilicity, antibacterial efficacy, and neovascularization. This study focuses on synthesis and material/biological characterization of rosemary (RM) and citric acid (CA) loaded PEO/GG hydrogel films. Scanning Electron Microscopy images confirmed the porous structure of the developed hydrogel film matrix (PEO/GG) and the dispersion of RM and CA within it. This porous structure promotes moisture adsorption, cell attachment, proliferation, and tissue layer formation. Fourier Transform Infrared Spectroscopy (FTIR) further validated the crosslinking of the PEO/GG matrix, as confirmed by the appearance of C-O-C linkage in the FTIR spectrum. PEO/GG and PEO/GG/RM/CA revealed similar degradation and release kinetics in Dulbecco's Modified Eagle Medium, Simulated Body Fluid, and Phosphate Buffer Saline (degradation of ∼55 % and release of ∼60 % RM in 168 h.). The developed hydrogel film exhibited a zone of inhibition against Escherichia. coli (2 mm) and Staphylococcus. aureus (9 mm), which can be attributed to the presence of RM in the hydrogel film. Furthermore, incorporating CA in the hydrogel film promoted neovascularization, as confirmed by the Chorioallantoic Membrane Assay. The developed RM and CA-loaded PEO/GG-based hydrogel films offered suitable in-vitro properties that may aid in potential wound healing applications.

Enhancing the selectivity for light olefins through catalytic cracking of n-hexane by phosphorus doping on lanthanum-modified ZSM-5.

Naphtha, as the primary raw material in the production of light olefins, could well accommodate their increasing demand through the energy-efficient process of catalytic cracking with ZSM-5. In the current work, different amounts of lanthanum and phosphorous were loaded on ZSM-5 using the wet impregnation method to tune the acidic properties of ZSM-5 for selective catalytic cracking of n-hexane to produce light olefins. Various characterization techniques such as X-ray diffraction (XRD), Al nuclear magnetic resonance (NMR), temperature-programmed desorption of NH3 (NH3-TPD), Py-Fourier transform infra-red (Py-FTIR), inductively coupled plasma optical emission spectroscopy (ICP-OES), N2 adsorption-desorption, X-ray photoelectron spectra (XPS), and scanning electron microscopy were adopted to investigate the modified zeolites. It was found that adding La to ZSM-5 (0.25 wt% to 1 wt%) improved the catalytic life and increased the n-hexane conversion (to 99.7%), while the further addition had a negative impact, reducing the conversion rate and deviating the product selectivity towards a substantial, undesired benzene, toluene, and xylene (BTX) fraction (33%). On the other hand, a 64% selectivity for light olefins was achieved on phosphorous-doped ZSM-5 (at a loading amount of 1 wt%) while reducing the BTX fraction (2.3%) and converting 69% of the n-hexane. A dual metal-modified ZSM-5 with optimal loading amount, 1P0.25LaZ5 (phosphorus 1 wt% and La 0.25 wt%), helped boost the light olefin selectivity to 62% in the tuned Lewis acid sites at an n-hexane conversion of about 77% while decreasing the undesired BTX selectivity to 3% by reducing the number of Brønsted sites. Thus, the current study reveals that tuning the acidic sites of ZMS-5 by dual metal augmentation with P.La is an effective way of controlling the amount of undesirable BTX produced at a stable n-hexane conversion rate and substantial olefin selectivity.

Correction to "Mitigation of Salinity Stress and Lead Toxicity in Maize by Exogenous Application of the Sorghum Water Extract".

[This corrects the article DOI: 10.1021/acsomega.3c09495.].

Multispectral breast image grayscale and quality enhancement by repeated pair image registration & accumulation method.

Nowadays, for detecting breast cancer in its early stages, the focus is on multispectral transmission imaging. Frame accumulation is a promising technique to enhance the grayscale level of the multispectral transmission images. Still, during the image acquisition process, human respiration or camera jitter causes the displacement of the frame's sequence which leads to the loss of accuracy and image quality of the frame accumulated image is reduced. In this article, we have proposed a new method named "repeated pair image registration and accumulation "to resolve the issue. In this method first pair of images from the sequence is first registered and accumulated followed by the next pair to be registered and accumulated. Then these two accumulated frames are registered and accumulated again. This process is repeated until all the frames from the sequence are processed and the final image is obtained. This method is tested on the sequence of breast frames taken at 600 nm, 620 nm, 670 nm, and 760 nm wavelength of light and proved the enhancement of quality, accuracy, and grayscale by various mathematical assessments. Furthermore, the processing time of our proposed method is very low because descent gradient optimization algorithm is used here for image registration purpose. This optimization algorithm has high speed as compared to other methods and is verified by registering a single image of each wavelength by three different methods. It has laid the foundations of early detection of breast cancer using multispectral transmission imaging.

Discovery of putative inhibitors of human Pkd1 enzyme: Molecular docking, dynamics and simulation, QSAR, and MM/GBSA.

Polycystic kidney disease is the most prevalent hereditary kidney disease globally and is mainly linked to the overexpression of a gene called PKD1. To date, there is no effective treatment available for polycystic kidney disease, and the practicing treatments only provide symptomatic relief. Discovery of the compounds targeting the PKD1 gene by inhibiting its expression under the disease condition could be crucial for effective drug development. In this study, a molecular docking and molecular dynamic simulation, QSAR, and MM/GBSA-based approaches were used to determine the putative inhibitors of the Pkd1 enzyme from a library of 1379 compounds. Initially, fourteen compounds were selected based on their binding affinities with the Pkd1 enzyme using MOE and AutoDock tools. The selected drugs were further investigated to explore their properties as drug candidates and the stability of their complex formation with the Pkd1 enzyme. Based on the physicochemical and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties, and toxicity profiling, two compounds including olsalazine and diosmetin were selected for the downstream analysis as they demonstrated the best drug-likeness properties and highest binding affinity with Pkd1 in the docking experiment. Molecular dynamic simulation using Gromacs further confirmed the stability of olsalazine and diosmetin complexes with Pkd1 and establishing interaction through strong bonding with specific residues of protein. High biological activity and binding free energies of two complexes calculated using 3D QSAR and Schrodinger module, respectively further validated our results. Therefore, the molecular docking and dynamics simulation-based in-silico approach used in this study revealed olsalazine and diosmetin as potential drug candidates to combat polycystic kidney disease by targeting Pkd1 enzyme.

Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction.

Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82-0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.

Salicylic Acid and Gemma-Aminobutyric Acid Mediated Regulation of Growth, Metabolites, Antioxidant Defense System and Nutrient Uptake in Sunflower (Helianthus annuus L.) Under Arsenic Stress.

Background: Arsenic (As) is a highly toxic and carcinogenic pollutant commonly found in soil and water, posing significant risks to human health and plant growth. Objective: The objectives of this study to evaluate morphological, biochemical, and physiological markers, as well as ion homeostasis, to alleviate the toxic effects of As in sunflowers through the exogenous application of salicylic acid (SA), γ-aminobutyric acid (GABA), and their combination. Methods: A pot experiment was conducted using two sunflower genotypes, FH-779 and FH-773, subjected to As stress (60 mg kg-1) to evaluate the effects of SA at 100 mg L-1, GABA at 200 mg L-1, and their combination on growth and related physiological and biochemical attributes under As stress. Results: The study revealed that As toxicity had a detrimental effect on various growth parameters, chlorophyll pigments, relative water content, total proteins, and nutrient uptake in sunflower plants. It also led to increased oxidative stress, as indicated by higher levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2), along with As accumulation in the roots and leaves. However, the application of SA and GABA protected against As-induced damage by enhancing the enzymatic antioxidant defense system. This was achieved through the activation of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities, as well as an increase in osmolytes. They also improved nutrient acquisition and plant growth under As toxicity. Conclusions: We investigated the regulatory roles of SA and GABA in mitigating arsenic-induced phytotoxic effects on sunflower. Our results revealed a significant interaction between SA and GABA in regulating growth, photosynthesis, metabolites, antioxidant defense systems, and nutrient uptake in sunflower under As stress. These findings provide valuable insights into plant defense mechanisms and strategies to enhance stress tolerance in contaminated environments. In the future, SA and GABA could be valuable tools for managing stress in other important crops facing abiotic stress conditions.