The impact of biochar addition on morpho-physiological characteristics, yield and water use efficiency of tomato plants under drought and salinity stress.

The use of saline water under drought conditions is critical for sustainable agricultural development in arid regions. Biochar is used as a soil amendment to enhance soil properties such as water-holding capacity and the source of nutrition elements of plants. Thus, the research was carried out to assess the impact of biochar treatment on the morphological and physiological characteristics and production of Solanum lycopersicum in greenhouses exposed to drought and saline stresses. The study was structured as a three-factorial in split-split-plot design. There were 16 treatments across three variables: (i) water quality, with freshwater and saline water, with electrical conductivities of 0.9 and 2.4 dS m- 1, respectively; (ii) irrigation level, with 40%, 60%, 80%, and 100% of total evapotranspiration (ETC); (iii) and biochar application, with the addition of biochar at a 3% dosage by (w/w) (BC3%), and a control (BC0%). The findings demonstrated that salt and water deficiency hurt physiological, morphological, and yield characteristics. Conversely, the biochar addition enhanced all characteristics. Growth-related parameters, such as plant height, stem diameter, leaf area, and dry and wet weight, and leaf gas exchange attributes, such rate of transpiration and photosynthesis, conductivity, as well as leaf relative water content were decreased by drought and salt stresses, especially when the irrigation was 60% ETc or 40% ETc. The biochar addition resulted in a substantial enhancement in vegetative growth-related parameters, physiological characteristics, efficiency of water use, yield, as well as reduced proline levels. Tomato yield enhanced by 4%, 16%, 8%, and 3% when irrigation with freshwater at different levels of water deficit (100% ETc, 80% ETc, 60% ETc, and 40% ETc) than control (BC0%). Overall, the use of biochar (3%) combined with freshwater shows the potential to enhance morpho-physiological characteristics, support the development of tomato plants, and improve yield with higher WUE in semi-arid and arid areas.

Clinical and Molecular Spectrum of Autosomal Recessive CA8-Related Cerebellar Ataxia.

BACKGROUND: Based on a limited number of reported families, biallelic CA8 variants have currently been associated with a recessive neurological disorder named, cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CAMRQ-3). OBJECTIVES: We aim to comprehensively investigate CA8-related disorders (CA8-RD) by reviewing existing literature and exploring neurological, neuroradiological, and molecular observations in a cohort of newly identified patients. METHODS: We analyzed the phenotype of 27 affected individuals from 14 families with biallelic CA8 variants (including data from 15 newly identified patients from eight families), ages 4 to 35 years. Clinical, genetic, and radiological assessments were performed, and zebrafish models with ca8 knockout were used for functional analysis. RESULTS: Patients exhibited varying degrees of neurodevelopmental disorders (NDD), along with predominantly progressive cerebellar ataxia and pyramidal signs and variable bradykinesia, dystonia, and sensory impairment. Quadrupedal gait was present in only 10 of 27 patients. Progressive selective cerebellar atrophy, predominantly affecting the superior vermis, was a key diagnostic finding in all patients. Seven novel homozygous CA8 variants were identified. Zebrafish models demonstrated impaired early neurodevelopment and motor behavior on ca8 knockout. CONCLUSION: Our comprehensive analysis of phenotypic features indicates that CA8-RD exhibits a wide range of clinical manifestations, setting it apart from other subtypes within the category of CAMRQ. CA8-RD is characterized by cerebellar atrophy and should be recognized as part of the autosomal-recessive cerebellar ataxias associated with NDD. Notably, the presence of progressive superior vermis atrophy serves as a valuable diagnostic indicator. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Current stage of preclinical and clinical development of guggulsterone in cancers: Challenges and promises.

Throughout human history, the utilization of medicinal herbs has been recognized as a crucial defense against various ailments, including cancer. Natural products with potential anticancer properties, capable of inducing apoptosis in cancer cells, have garnered substantial attention. One such agent under investigation is guggulsterone (GS), a phytosterol derived from the gum resin of the Commiphora mukul tree. This review aims to provide a comprehensive summary of recent studies elucidating the anticancer molecular mechanisms and molecular targets of GS, guiding future research and potential applications as an adjuvant drug in cancer therapy. Recent in vivo and in vitro studies have explored the biological activities of the active ingredients in Commiphora mukul. Specifically, GS emerges as a potential cancer chemopreventive and therapeutic agent. The investigations delve into the impact of GS on constitutively activated survival pathways, including Janus kinase/signal transducer and activator of transcription (JAK/STAT), nuclear factor-kappa B (NF-kB), and PI3-kinase/AKT signaling pathways. These pathways regulate antiapoptotic and proinflammatory genes, exerting control over growth and inflammatory responses. The findings highlight the potential of GS in disrupting survival pathways crucial for cancer cell viability. The inhibition of JAK/STAT, NF-kB, and PI3-kinase/AKT signaling pathways positions GS as a promising candidate for cancer therapy. The review synthesizes evidence from diverse studies, underscoring the multifaceted biological activities of GS in cancer prevention and treatment. To advance our understanding, future clinical and translational studies are imperative to determine effective doses in humans. Additionally, there is a need for the development of new pharmaceutical forms of GS to optimize therapeutic effects. This comprehensive review provides a foundation for ongoing research, offering insights into the potential of GS as a valuable addition to the armamentarium against cancer.

Role of estrogen in sex differences in memory, emotion and neuropsychiatric disorders.

Estrogen regulates a wide range of neuronal functions in the brain, such as dendritic spine formation, remodeling of synaptic plasticity, cognition, neurotransmission, and neurodevelopment. Estrogen interacts with intracellular estrogen receptors (ERs) and membrane-bound ERs to produce its effect via genomic and non-genomic pathways. Any alterations in these pathways affect the number, size, and shape of dendritic spines in neurons associated with psychiatric diseases. Increasing evidence suggests that estrogen fluctuation causes changes in dendritic spine density, morphology, and synapse numbers of excitatory and inhibitory neurons differently in males and females. In this review, we discuss the role of estrogen hormone in rodents and humans based on sex differences. First, we explain estrogen role in learning and memory and show that a high estrogen level alleviates the deficits in learning and memory. Secondly, we point out that estrogen produces a striking difference in emotional memories in men and women, which leads them to display sex-specific differences in underlying neuronal signaling. Lastly, we discuss that fluctuations in estrogen levels in men and women are related to neuropsychiatric disorders, including schizophrenia, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BPD), major depressive disorder (MDD), substance use disorder (SUD), and anxiety disorders.

Surgical strategies in acute subdural hematoma: a meta-analysis of decompressive craniectomy vs. craniotomy.

OBJECTIVE: Acute subdural hematoma (ASDH) stands as a significant contributor to morbidity after severe traumatic brain injuries (TBI). The primary treatment approach for patients experiencing progressive neurological deficits or notable mass effects is the surgical removal of the hematoma, which can be achieved through craniotomy (CO) or decompressive craniectomy (DC). Nevertheless, the choice between these two procedures remains a subject of ongoing debate and controversy. MATERIALS AND METHODS: We conducted a comprehensive literature review, utilizing prominent online databases and manually searching references related to craniotomy and craniectomy for subdural hematoma evacuation up to November 2023. Our analysis focused on outcome variables such as the presence of residual subdural hematoma, the need for revision procedures, and overall clinical outcomes. RESULTS: We included a total of 11 comparative studies in our analysis, encompassing 4269 patients, with 2979 undergoing craniotomy and 1290 undergoing craniectomy, meeting the inclusion criteria. Patients who underwent craniectomy displayed significantly lower scores on the Glasgow Coma Scale (GCS) during their initial presentation. Following surgery, the DC group exhibited a significantly reduced rate of residual subdural (P = 0.009). Additionally, the likelihood of a poor outcome during follow-up was lower in the CO group. Likewise, the mortality rate was lower in the CO group compared to the craniectomy group (OR 0.63, 95% CI 0.41-0.98, I2 = 84%, P = 0.04). CONCLUSION: Our study found that CO was associated with more favorable outcomes in terms of mortality, reoperation rate, and functional outcome while DC was associated with less likelihood of residual subdural hematoma. Upon further investigation of patient characteristics who underwent into either of these interventions, it was very clear that patients in DC cohort have more serious and low pre-op characteristics than the CO group. Nonetheless, brain herniation and advanced age act as independent factor for predicting the outcome irrespective of the intervention.

A comparison of continuous cold flow and compression device and traditional icing regimen and no icing following anterior cruciate ligament reconstruction: A pilot study.

The aim of this study was to investigate the effectiveness of continuous cold flow and compression device as against traditional icing regimen and without icing after anterior cruciate ligament (ACL) reconstruction. All patients undergoing ACL reconstruction from June 2021 to August 2021 were enrolled in this study. Patients were randomly allocated to three groups: A control group (n=10) with no ice regimen post-operatively, a second control group (n=10) with ice bag, and a third group (n=10) with continuous cold flow and compression device (physiolab). All patients who had isolated ACL tear evident on magnetic resonance imaging were included. Pain intensity, limb girth, Oxford Knee Score, and 12-item survey form were measured pre- and post-operatively. Significant difference was noted between pain scores in all groups at two- and six-week follow-ups with p-value of 0.004 and 0.01. The test for "between subject effects" showed significant difference (p=0.007) in limb girth between the two groups. Cold and compression device can be used to reduce swelling immediately after ACL reconstruction.

Cochlear duct length in Pakistani cochlear implant recipients gender, age and side association: A Radiological Measure.

Objectives: To analyze the gender, age and side association of cochlear duct length in Pakistani-Asian cochlear implant recipient population based on computed tomography imaging study. Methods: Current study retrospectively studied charts of cases who underwent cochlear implantation at the Department of Otolaryngology & Auditory Implant Centre, Capital Hospital Islamabad, over a period of two years from 1st May 2017 to 30th April 2019. These included 200 cases of both genders and of any age. In addition to basic demographic data, computed tomography findings of the temporal bone were utilized to measure the cochlear duct length. Data was analyzed using SPSS Version 23. Results: Study revealed a mean Cochlear duct length of 29.935±2.173mm (range: 25.12 to 37.60) with significant (p<0.001) association with gender with longer cochlear duct in males compared to females on right (30.50±2.384 vs. 29.36±1.887) and on left side (30.50±2.236 vs.29.32±1.935). However, no significant difference was noted for side with slightly longer cochlear duct on the right side compared to left (29.95±2.224 vs.29.92±2.171). Also, no significant association with age was noted with p=0.578 & p=0.824 for right and left side respectively. Conclusion: Pakistani population is characterized by a short mean CDL of 29.935±2.173 mm with significant association (p<0.001) with gender with longer cochlear duct length in males; and side with larger CDL on right side. However, no significant association with age was noted.

Microbes-mediated synthesis strategies of metal nanoparticles and their potential role in cancer therapeutics.

Past few years have seen a paradigm shift towards ecofriendly, green and biological fabrication of metal nanoparticles (MNPs) for diverse nanomedicinal applications especially in cancer nanotheranostics. Besides, the well-known green synthesis methods of plant materials, the potential of the microbial world (bacteria, fungi, alga, etc.) in biofabrication is equally realized. Biomolecules and enzymes in the microbial cells are capable of catalyzing the biosynthesis process. These microbial derived inorganic nanoparticles have been frequently evaluated as potential agents in cancer therapies revealing exciting results. Through, cellular and molecular pathways, these microbial derived nanoparticles are capable of killing the cancer cells. Considering the recent developments in the anticancer applications of microbial derived inorganic MNPs, a dire need was felt to bring the available information to a single document. This manuscript reviews not only the mechanistic aspects of the microbial derived MNPs but also include the diverse mechanisms that governs their anticancer potential. Besides, an updated literature review is presented that includes studies of 2019-onwards.

Differential regulation of hippocampal transcriptome by circulating estrogen.

Estrogen (E2) modulates the synaptic structure and plasticity in the hippocampus. Previous studies showed that E2 fluctuations during various phases of the menstrual cycle produce subtle neurosynaptic changes that impact women's behavior, emotion, and cognitive functions. In this study, we explored the transcriptome of the hippocampus via RNA-seq (RNA-sequencing) between proestrus (PE) and diestrus (DE) stages in young female rats to determine the effect of E2 of PE and DE stages on hippocampal gene expression. We identified 238 genes (at 1.5-fold-change selection criteria, FDR adjusted p-value < 0.05) as differentially expressed genes (DEGs) that responded to E2 between PE and DE stages. Functional analysis based on Gene Ontology (GO) revealed that a higher E2 level corresponded to an increase in gene transcription among most of the DEGs, suggesting biological mechanisms operating differentially in the hippocampus of female rats between PE and DE stages in the estrus cycle; while analysis with Kyoto Encyclopedia of Genes and Genomes database (KEGG) found that the DEGs involving neuroactive ligand-receptor interaction, antigen processing, cell adhesion molecules, and presentation were upregulated in PE stage, whereas DEGs in pathways relating to bile secretion, coagulation cascades, osteoclast differentiation, cysteine and methionine metabolism were upregulated in DE stage of the estrus cycle. The high-fold expression of DEGs was confirmed by a follow-up quantitative real-time PCR. Our findings in this current study have provided fundamental information for further dissection of neuro-molecular mechanisms in the hippocampus in response to E2 fluctuation and its relationship with disorders.

Gender concordance and publication productivity within Neurosurgical Focus: a 10-year review (2013-2022).

OBJECTIVE: The "leaky academic pipeline" describes how female representation in leadership positions has remained stagnant despite an increase in the number of female trainees. Female mentorship to female mentees, and female role models at higher academic positions have been shown to positively influence academic productivity. To the authors' knowledge, the impact of female editorial board representation on authorship trends in neurosurgical journals remains undescribed. This study aimed to analyze trends in the representation of female topic editors and its impact on female authorship within Neurosurgical Focus over a 10-year period. METHODS: Publicly available data were collected from the journal's website, inclusive from January 2013 to December 2022. The articles were grouped into technical and nontechnical themes based on their relevance to specific technical details regarding surgical techniques. Female gender-concordant publications were defined as publications having a female first author (or co-first author) and a female senior author. Linear regression analysis determined trends in publishing. Odds ratios and 95% CIs were calculated using logistic regression analysis. Pearson correlation and cross-correlation analyses were used to examine each pairwise comparison of time series. The statistical significance of associations was evaluated using t-tests and chi-square and Fisher's exact tests. RESULTS: The number of female topic editors and gender-concordant authors increased over time (p < 0.05). Women accounted for ≥ 50% of the topic editors on nontechnical themes relevant to education and gender diversity. Having a female senior author was associated with higher publication productivity for original research and review articles among female authors (OR 13.73, 95% CI 1.75-394.31; p < 0.05). Female authors had higher odds of publishing editorials with a female topic editor (OR 3.81, 95% CI 1.37-11.02; p < 0.01). Publications with female first and senior authors were significantly more likely to have female topic editors (OR 4.05, 95% CI 1.38-12.92; p < 0.01). A positive association was observed between female senior authors and female topic editors at lag -8, with a correlation coefficient of 0.19 (p = 0.03). CONCLUSIONS: Female attending-to-female trainee mentorship and female representation among editorial boards play a crucial role in enhancing academic productivity among women. Efforts to sustain academic productivity during the early-career period would presumably help increase female representation in neurosurgery.

Optimizing Machine Learning Algorithms for Landslide Susceptibility Mapping along the Karakoram Highway, Gilgit Baltistan, Pakistan: A Comparative Study of Baseline, Bayesian, and Metaheuristic Hyperparameter Optimization Techniques.

Algorithms for machine learning have found extensive use in numerous fields and applications. One important aspect of effectively utilizing these algorithms is tuning the hyperparameters to match the specific task at hand. The selection and configuration of hyperparameters directly impact the performance of machine learning models. Achieving optimal hyperparameter settings often requires a deep understanding of the underlying models and the appropriate optimization techniques. While there are many automatic optimization techniques available, each with its own advantages and disadvantages, this article focuses on hyperparameter optimization for well-known machine learning models. It explores cutting-edge optimization methods such as metaheuristic algorithms, deep learning-based optimization, Bayesian optimization, and quantum optimization, and our paper focused mainly on metaheuristic and Bayesian optimization techniques and provides guidance on applying them to different machine learning algorithms. The article also presents real-world applications of hyperparameter optimization by conducting tests on spatial data collections for landslide susceptibility mapping. Based on the experiment's results, both Bayesian optimization and metaheuristic algorithms showed promising performance compared to baseline algorithms. For instance, the metaheuristic algorithm boosted the random forest model's overall accuracy by 5% and 3%, respectively, from baseline optimization methods GS and RS, and by 4% and 2% from baseline optimization methods GA and PSO. Additionally, for models like KNN and SVM, Bayesian methods with Gaussian processes had good results. When compared to the baseline algorithms RS and GS, the accuracy of the KNN model was enhanced by BO-TPE by 1% and 11%, respectively, and by BO-GP by 2% and 12%, respectively. For SVM, BO-TPE outperformed GS and RS by 6% in terms of performance, while BO-GP improved results by 5%. The paper thoroughly discusses the reasons behind the efficiency of these algorithms. By successfully identifying appropriate hyperparameter configurations, this research paper aims to assist researchers, spatial data analysts, and industrial users in developing machine learning models more effectively. The findings and insights provided in this paper can contribute to enhancing the performance and applicability of machine learning algorithms in various domains.

Power-Intent Systolic Array Using Modified Parallel Multiplier for Machine Learning Acceleration.

Systolic arrays are an integral part of many modern machine learning (ML) accelerators due to their efficiency in performing matrix multiplication that is a key primitive in modern ML models. Current state-of-the-art in systolic array-based accelerators mainly target area and delay optimizations with power optimization being considered as a secondary target. Very few accelerator designs directly target power optimizations and that too using very complex algorithmic modifications that in turn result in a compromise in the area or delay performance. We present a novel Power-Intent Systolic Array (PI-SA) that is based on the fine-grained power gating of the multiplication and accumulation (MAC) block multiplier inside the processing element of the systolic array, which reduces the design power consumption quite significantly, but with an additional delay cost. To offset the delay cost, we introduce a modified decomposition multiplier to obtain smaller reduction tree and to further improve area and delay, we also replace the carry propagation adder with a carry save adder inside each sub-multiplier. Comparison of the proposed design with the baseline Gemmini naive systolic array design and its variant, i.e., a conventional systolic array design, exhibits a delay reduction of up to 6%, an area improvement of up to 32% and a power reduction of up to 57% for varying accumulator bit-widths.

Klotho Regulated by Estrogen Plays a Key Role in Sex Differences in Stress Resilience in Rats.

Klotho (KL) is a glycosyl hydrolase and aging-suppressor gene. Stress is a risk factor for depression and anxiety, which are highly comorbid with each other. The aim of this study is to determine whether KL is regulated by estrogen and plays an important role in sex differences in stress resilience. Our results showed that KL is regulated by estrogen in rat hippocampal neurons in vivo and in vitro and is essential for the estrogen-mediated increase in the number of presynaptic vesicular glutamate transporter 1 (Vglut1)-positive clusters on the dendrites of hippocampal neurons. The role of KL in sex differences in stress response was examined in rats using 3-week chronic unpredictable mild stress (CUMS). CUMS produced a deficit in spatial learning and memory, anhedonic-like behaviors, and anxiety-like behaviors in male but not female rats, which was accompanied by a reduction in KL protein levels in the hippocampus of male but not female rats. This demonstrated the resilience of female rats to CUMS. Interestingly, the knockdown of KL protein levels in the rat hippocampus of both sexes caused a decrease in stress resilience in both sexes, especially in female rats. These results suggest that the regulation of KL by estrogen plays an important role in estrogen-mediated synapse formation and that KL plays a critical role in the sex differences in cognitive deficit, anhedonic-like behaviors, and anxiety-like behaviors induced by chronic stress in rats, highlighting an important role of KL in sex differences in stress resilience.

Co-Loading of Black Phosphorus Nanoflakes and Doxorubicin in Lysolipid Temperature-Sensitive Liposomes for Combination Therapy in Prostate Cancer.

Black phosphorus (BP) is one of the most promising nanomaterials for cancer therapy. This 2D material is biocompatible and has strong photocatalytic activity, making it a powerful photosensitiser for combined NIR photothermal and photodynamic therapies. However, the fast degradation of BP in oxic conditions (including biological environments) still limits its use in cancer therapy. This work proposes a facile strategy to produce stable and highly concentrated BP suspensions using lysolipid temperature-sensitive liposomes (LTSLs). This approach also allows for co-encapsulating BP nanoflakes and doxorubicin, a potent chemotherapeutic drug. Finally, we demonstrate that our BP/doxorubicin formulation shows per se high antiproliferative action against an in vitro prostate cancer model and that the anticancer activity can be enhanced through NIR irradiance.

Oscillatoria limnetica Mediated Green Synthesis of Iron Oxide (Fe2O3) Nanoparticles and Their Diverse In Vitro Bioactivities.

Iron oxide nanoparticles (Fe2O3-NPs) were synthesized using Oscillatoria limnetica extract as strong reducing and capping agents. The synthesized iron oxide nanoparticles IONPs were characterized by UV-visible spectroscopy, Fourier transform infrared (FTIR), X-ray diffractive analysis (XRD), scanning electron microscope (SEM), and Energy dispersive X-ray spectroscopy (EDX). IONPs synthesis was confirmed by UV-visible spectroscopy by observing the peak at 471 nm. Furthermore, different in vitro biological assays, which showed important therapeutic potentials, were performed. Antimicrobial assay of biosynthesized IONPs was performed against four different Gram-positive and Gram-negative bacterial strains. E. coli was found to be the least suspected strain (MIC: 35 µg/mL), and B. subtilis was found to be the most suspected strain (MIC: 14 µg/mL). The maximum antifungal assay was observed for Aspergillus versicolor (MIC: 27 µg mL). The cytotoxic assay of IONPs was also studied using a brine shrimp cytotoxicity assay, and LD50 value was reported as 47 µg/mL. In toxicological evaluation, IONPs was found to be biologically compatible to human RBCs (IC50: >200 µg/mL). The antioxidant assay, DPPH 2,2-diphenyl-1-picrylhydrazyly was recorded at 73% for IONPs. In conclusion, IONPs revealed great biological potential and can be further recommended for in vitro and in vivo therapeutic purposes.

Exploring Physical Characterization and Different Bio-Applications of Elaeagnus angustifolia Orchestrated Nickel Oxide Nanoparticles.

Elaeagnus angustifolia (EA) mediated green chemistry route was used for the biofabrication of NiONPs without the provision of additional surfactants and capping agents. The formation of NiONPs was confirmed using advanced different characterization techniques such as Scanning electron microscopy, UV, Fourier transmission-infrared, RAMAN, and energy dispersal spectroscopic and dynamic light scattering techniques. Further, different biological activities of EA-NiONPs were studied. Antibacterial activities were performed using five different bacterial strains using disc-diffusion assays and have shown significant results as compared to standard Oxytetracycline discs. Further, NiONPs exhibited excellent antifungal performance against different pathogenic fungal strains. The biocompatibility test was performed using human RBCs, which further confirmed that NiONPs are more biocompatible at the concentration of 7.51-31.25 µg/mL. The antioxidant activities of NiONPs were investigated using DPPH free radical scavenging assay. The NiONPs were demonstrated to have much better antioxidant potentials in terms of % DPPH scavenging (93.5%) and total antioxidant capacity (81%). Anticancer activity was also performed using HUH7 and HEP-G2 cancer cell lines and has shown significant potential with IC50 values of 18.45 µg/mL and 14.84 µg/mL, respectively. Further, the NiONPs were evaluated against Lesihmania tropica parasites and have shown strong antileishmanial potentials. The EA-NiONPs also showed excellent enzyme inhibition activities; protein kinase (19.4 mm) and alpha-amylase (51%). In conclusion, NiONPs have shown significant results against different biological assays. In the future, we suggest various in vivo activities for EA-NiONPs using different animal models to further unveil the biological and biomedical potentials.

Fabrication and Characterization of Ag-Graphene Nanocomposites and Investigation of Their Cytotoxic, Antifungal and Photocatalytic Potential.

In the present study, we aimed to synthesize (Ag)1-x(GNPs)x nanocomposites in variable ratios (25% GNPs-Ag, 50% GNPs-Ag, and 75% GNPs-Ag) via an ex situ approach to investigate the incremental effects of GNPs (graphene nanoparticles) on AgNPs (silver nanoparticles). The prepared nanocomposites were successfully characterized using different microscopic and spectroscopic techniques, including X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, ultraviolet spectroscopy, and Raman spectroscopic analysis. For the evaluation of morphological aspects, shape, and percentage elemental composition, SEM and EDX analyses were employed. The bioactivities of the synthesized nanocomposites were briefly investigated. The antifungal activity of (Ag)1-x(GNPs)x nanocomposites was reported to be 25% for AgNPs and 66.25% using 50% GNPs-Ag against Alternaria alternata. The synthesized nanocomposites were further evaluated for cytotoxic potential against U87 cancer cell lines with improved results (for pure AgNPs IC50: ~150 µg/mL, for 50% GNPs-Ag IC50: ~12.5 µg/mL). The photocatalytic properties of the nanocomposites were determined against the toxic dye Congo red, and the percentage degradation was recorded as 38.35% for AgNPs and 98.7% for 50% GNPs-Ag. Hence, from the results, it is concluded that silver nanoparticles with carbon derivatives (graphene) have strong anticancer and antifungal properties. Dye degradation strongly confirmed the photocatalytic potential of Ag-graphene nanocomposites in the removal of toxicity present in organic water pollutants.

GIS based hotspot analysis and health risk assessment of groundwater arsenic from an unconfined deep aquifer of Lahore, Pakistan.

Use of groundwater for drinking purpose poses serious hazards of arsenic contamination particularly in plains of western Himalayan region. Therefore, current study was designed to investigate the level of Arsenic (As) in the water obtained from tubewells in a metropolitan city of Lahore, Pakistan and assess the human health risk. So, a total of 73 tubewells were sampled randomly in the manner that the whole study region was covered without any clustering. The water samples were analyzed for As using atomic absorption spectrophotometer. These samples were also tested for total dissolved solids, chlorides, pH, alkalinity, turbidity, hardness and calcium. GIS based hotspots analysis technique was used to investigate the spatial distribution patterns. Our results revealed that only one sample out of total 73 had arsenic level below the WHO guideline of 10 µg/L. The spatial distribution map of arsenic revealed that the higher concentrations of arsenic are present in the north-western region of Lahore. The cluster and outlier analysis map using Anselin Local Moran's I statistic indicated the presence of an arsenic cluster in the west of River Ravi. Furthermore, the optimized hotspot analysis based on Getis-Ord Gi* statistics confirmed the statistical significance (P < 0.05) and (P < 0.01) of these samples from the vicinity of River Ravi. Regression analysis showed that variables such as turbidity, alkalinity, hardness, chlorides, calcium and total dissolved solids were significantly (all P < 0.05) associated with level of Arsenic in tubewells. Whereas, PH and electrical conductivity and other variables like town, year of installation, depth and diameter of the wells were not significantly associated with Arsenic concentrations in tubewells. Principal component analysis (PCA) exhibited that the random distribution of tubewell samples showed no distinct clustering with towns studied. Health risk assessment based on hazard and Cancer risk index revealed serious risk of developing carcinogenic and non-carcinogenic diseases particularly in children. The health risk due to prevalence of high As concentration in tubewells' water need to be mitigated immediately to avoid worst consequences in future.

Hydrogeochemistry and prediction of arsenic contamination in groundwater of Vehari, Pakistan: comparison of artificial neural network, random forest and logistic regression models.

Arsenic contamination in the groundwater occurs in various parts of the world due to anthropogenic and natural sources, adversely affecting human health and ecosystems. The current study intends to examine the groundwater hydrogeochemistry containing elevated arsenic (As), predict As levels in groundwater, and determine the aptness of groundwater for drinking in the Vehari district, Pakistan. Four hundred groundwater samples from the study region were collected for physiochemical analysis. As levels in groundwater samples ranged from 0.1 to 52 µg/L, with an average of 11.64 µg/L, (43.5%), groundwater samples exceeded the WHO 2022 recommended limit of 10 µg/L for drinking purposes. Ion-exchange processes and the adsorption of ions significantly impacted the concentration of As. The HCO3- and Na+ are the dominant ions in the study area, and the water types of samples were CaHCO3, mixed CaMgCl, and CaCl, demonstrating that rock-water contact significantly impacts hydrochemical behavior. The geochemical modeling indicated negative saturation indices with calcium carbonate and other salt minerals, encompassing aragonite, calcite, dolomite, and halite. The dissolution mechanism suggested that these minerals might have implications for the mobilization of As in groundwater. A combination of human-induced and natural sources of contamination was unveiled through principal component analysis (PCA). Artificial neural networks (ANN), random forest (RF), and logistic regression (LR) were used to predict As in the groundwater. The data have been divided into two parts for statistical analysis: 20% for testing and 80% for training. The most significant input variables for As prediction was determined using Chi-squared analysis. The receiver operating characteristic area under the curve and confusion matrix were used to evaluate the models; the RF, ANN, and LR accuracies were 0.89, 0.85, and 0.76. The permutation feature and mean decrease in impurity determine ten parameters that influence groundwater arsenic in the study region, including F-, Fe2+, K+, Mg2+, Ca2+, Cl-, SO42-, NO3-, HCO3-, and Na+. The present study shows RF is the best model for predicting groundwater As contamination in the research area. The water quality index showed that 161 samples represent poor water, and 121 samples are unsuitable for drinking. Establishing effective strategies and regulatory measures is imperative in Vehari to ensure the sustainability of groundwater resources.

Exploring the inhibitory potential of novel piperidine-derivatives against main protease (Mpro) of SARS-CoV-2: A hybrid approach consisting of molecular docking, MD simulations and MMPBSA analysis.

In the current study, a hybrid computational approach consisting of different computational methods to explore the molecular electronic structures, bioactivity and therapeutic potential of piperidine compounds against SARS-CoV-2. The quantum chemical methods are used to study electronic structures of designed derivatives, molecular docking methods are used to see the most potential docking interactions for main protease (MPro) of SARS-CoV-2 while molecular dynamic and MMPBSA analyses are performed in bulk water solvation process to mimic real protein like aqueous environment and effectiveness of docked complexes. We designed and optimized piperidine derivatives from experimentally known precursor using quantum chemical methods. The UV-Visible, IR, molecular orbitals, molecular electrostatic plots, and global chemical reactivity descriptors are carried out which illustrate that the designed compounds are kinetically stable and reactive. The results of MD simulations and binding free energy revealed that all the complex systems possess adequate dynamic stability, and flexibility based on their RMSD, RMSF, radius of gyration, and hydrogen bond analysis. The computed net binding free energy ( Δ G b i n d ) as calculated by MMPBSA method for the complexes showed the values of -4.29 kcal.mol-1 for P1, -5.52 kcal.mol-1 for P2, -6.12 kcal.mol-1 for P3, -6.35 kcal.mol-1 for P4, -5.19 kcal.mol-1 for P5, 3.09 kcal.mol-1 for P6, -6.78 kcal.mol-1 for P7, and -6.29 kcal.mol-1 for P8.The ADMET analysis further confirmed that none of among the designed ligands violates the Lipinski rule of five (RO5). The current comprehensive investigation predicts that all our designed compounds are recommended as prospective therapeutic drugs against Mpro of SARS-CoV-2 and it provokes the scientific community to further perform their in-vitro analysis.