Search

Abstract This work implements the recently developed nth state Markovian jumping particle swarm optimisation (PSO) algorithm with local search (NS-MJPSOloc) awareness method to address the economic/environmental dispatch (EED) problem. The proposed approach, known as the Non-dominated Sorting Multi-objective PSO with Local Best (NS-MJPSOloc), aims to enhance the performance of the PSO algorithm in multi-objective optimisation problems. This is achieved by redefining the concept of best local candidates within the search space of multi-objective optimisation. The NS-MJPSOloc algorithm uses an evolutionary factor-based mechanism to identify the optimum compromise solution, a Markov chain state jumping technique to control the Pareto-optimal set size, and a neighbourhood’s topology (such as a ring or a star) to determine its size. Economic dispatch refers to the systematic allocation of available power resources in order to fulfill all relevant limitations and effectively meet the demand for electricity at the lowest possible operating cost. As a result of heightened public consciousness regarding environmental pollution and the implementation of clean air amendments, nations worldwide have compelled utilities to adapt their operational practises in order to comply with environmental regulations. The (NS-MJPSOloc) approach has been utilised for resolving the EED problem, including cost and emission objectives that are not commensurable. The findings illustrate the efficacy of the suggested (NS-MJPSOloc) approach in producing a collection of Pareto-optimal solutions that are evenly dispersed within a single iteration. The comparison of several approaches reveals the higher performance of the suggested (NS-MJPSOloc) in terms of the diversity of the Pareto-optimal solutions achieved. In addition, a measure of solution quality based on Pareto optimality has been incorporated. The findings validate the effectiveness of the proposed (NS-MJPSOloc) approach in addressing the multi-objective EED issue and generating a trade-off solution that is both optimal and of high quality. We observed that our approach can reduce $$\sim $$ ∼ 6.4% of fuel costs and $$\sim $$ ∼ 9.1% of computational time in comparison to the classical PSO technique. Furthermore, our method can reduce $$\sim $$ ∼ 9.4% of the emissions measured in tons per hour as compared to the PSO approach.

The present study was designed to improve the aqueous solubility and dissolution rate of citreorosein, a poorly water soluble drug, by producing its nanoparticles (NPs) using an “antisolvent precipitation with a syringe pump” (APSP) method. Various process parameters including flow rate, stirring speed, temperature, drug concentration and solvent-antisolvent ratio were investigated and optimized to obtain the smallest particle size of citreorosein. The prepared NPs were subjected to different analytical techniques such as SEM, FTIR, XRD and DLS. The NPs were tested for different dissolution parameters including difference (f1) and similarity factors (f2), dissolution efficiency (DE) and mean dissolution time (MDT). The antioxidant potential of citreorosein and its NPs were evaluated using DPPH, ABTS, and FRAP models, while their cytotoxicity was tested on various cancer cell lines such as breast (MDA-MB-231), lung (A549) and liver (HepG2), using the MTT assay. The specificity of the test compound was investigated against two normal human primary epithelial cells including renal (HRPTEpiC) and alveolar (HPAEpiC) cells. DLS analysis revealed that the prepared NPs were less than 200 nm in size while SEM and XRD confirmed their rod shape and amorphous nature, respectively. Citreorosein-NPs exhibited enhanced solubility and dissolution rate in all medias as compared to pure citreorosein. The NPs displayed significant antioxidant effects against ABTS, DPPH and FRAP models, with IC50 values of22.6, 21.45 and 27.30 µg/ml, respectively. Moreover, it showed significant cytotoxic activity against MDA-MB-231, A549 and HepG2 cells, with IC50 values of 3.45, 4.5 and 6.23 µg/ml, respectively. Furthermore, the NPs demonstrated high selectivity index values for the aforementioned cell lines as compared to reference drugs. This study demonstrated that APSP method successfully produced citreorosein-NPs and hence, showed better aqueous solubility, dissolution rate, antioxidant and cytotoxic activities than the pure compound.

In the present study, 30 potential germplasm of oat (Avena sativa L.) were subjected to proximate, elemental, and HPLC analysis to provide a scientific basis to genetic diversity present among them. The extracts of the selected germplasms were also evaluated for their antioxidant potentials through DPPH and ABTS assays. Proximate analysis showed protein contents to be in the range 8.35–17.72% with the highest protein contents in the accession line 22,365 (17.72 ± 0.38%). The genotype-725 showed the highest carbohydrate, and dry matter (53.35 ± 0.01 and 93.50 ± 0.07% respectively) contents whereas, the germplasm-830 contained the highest fat (7.88 ± 0.12%) contents while the highest moisture contents were there in germplasm-22348 (11.95 ± 0.06%). The crude fiber contents (19.67 ± 0.19%) were found high in germplasm-832. The mentioned contents were also correlated to each other where a negative (−0.431*) correlation was noted for crude protein and carbohydrate while ash content to crude protein has a positive (0.38*) correlation. A positive and a negative correlation were there in Crude fats/crude protein (0.30*) and crude fats/moisture contents (−0.39*) respectively. Principal component analysis showed an Eigenvalue of 0.76 with a total variation of 85.01% when applied to proximate components. Based on cluster analysis to proximate composition all the oat germplasms were divided into 5 sub-clusters, where accession numbers 769 and 817 were found to be the most diverse genotypes. The elemental analysis confirmed the presence of magnesium (2.89–7.62 mg/L), sodium (3.71–8.03 mg/L), manganese (0.93–3.71 mg/L), copper (0.35–3.36 mg/L), iron (2.15–6.82 mg/L), zinc (1.30–3.37 mg/L), chromium (0.37–3.34 mg/L), and potassium (50.70–59.60 mg/L) in the selected germplasms. Principal component analysis for elemental composition showed the total variation of 73.75% with the Eigenvalue of 0.97. Cluster analysis on an elemental basis divided all the oat germplasms into 7 sub-clusters where accession numbers 769 and 22,350 were found to be the most diverse germplasm. Phytochemical analysis performed through HPLC resulted in the identification of nine possible compounds (malic acid, epigallocatechin gallate, quercetin, morin, ellagic acid, catechin hydrate, rutin, pyrogallol, and mandelic acid) in various germplasm of oat. A concentration-dependent antioxidant response was recorded when extracts were tested as an inhibitor of DPPH and ABTS free radicals. The results revealed that oat grains are a good source of nutrients, minerals, and phytochemicals that can be used as nutraceuticals and as food. The genetic differences revealed that this plant can be grown under varied environmental conditions.

Pashtu is one of the most widely spoken languages in south-east Asia. Pashtu Numerics recognition poses challenges due to its cursive nature. Despite this, employing a machine learning-based optical character recognition (OCR) model can be an effective way to tackle this issue. The main aim of the study is to propose an optimized machine learning model which can efficiently identify Pashtu numerics from 0–9. The methodology includes data organizing into different directories each representing labels. After that, the data is preprocessed i.e., images are resized to 32 × 32 images, then they are normalized by dividing their pixel value by 255, and the data is reshaped for model input. The dataset was split in the ratio of 80:20. After this, optimized hyperparameters were selected for LSTM and CNN models with the help of trial-and-error technique. Models were evaluated by accuracy and loss graphs, classification report, and confusion matrix. The results indicate that the proposed LSTM model slightly outperforms the proposed CNN model with a macro-average of precision: 0.9877, recall: 0.9876, F1 score: 0.9876. Both models demonstrate remarkable performance in accurately recognizing Pashtu numerics, achieving an accuracy level of nearly 98%. Notably, the LSTM model exhibits a marginal advantage over the CNN model in this regard. [ABSTRACT FROM AUTHOR]

Parasites are a significant component of biodiversity. They negatively affect fish appearance, growth, and reproduction. In this study, the prevalence of infection, diversity, and mean intensity of parasites were examined in 9 freshwater fish species (45 samples per fish species). Ecto-parasites were examined on the skin, gills, and fins with a hand lens. Wet mounts were prepared using mucosal scrapings from all the external and internal organs of the sampled fish. Microscopy, muscle compression, and the pepsin-HCL artificial digestion technique were also performed. In this study, 26 species of parasites were identified including three taxa belonging to 9 species of protozoan parasites, 11 treamtodes, and 6 monogenean parasites. The identified protozoan parasites were Entamoeba histolitica, Chilodonella sp., Coccidia sp., Costia sp., Cryptobia sp., Ichthyopthiris-multifilis, Microsporidia, Piscinoodinium sp., and Ichthyobodo necator. The identified trematode parasites were Fasciola gigantica, Echinostoma revolutum, Fasciola hepatica, Haplorchis pumilio, Brachylaima cribbi, Echinostoma cinetorchis, Neascus sp., Deropegus sp., Trematode Soldier, Centrocestus formosanus, and Clinostomum marginatum. The identified monogenean parasites were Dactylogyrus limipopoensis, Dactylogyrus anchoratus, Dactylogyrus myersi, Dactylogyrus vastator, Gyrodactylus salaris, and Ancyrocephalus. The diversity of parasites was maximum at the Okara site. The host’s organs that were targeted for parasitic infection included the intestine, liver, gills, fins, skin, and kidneys. The majority of the parasites were identified in Labeo rohita followed by Hypophthalmichthys molitrix, Ctenopharyngodon idella, Oreochromis niloticus, Cyprinus carpio, and Wallagu attu. Two species appeared to be resistant species because none of the parasites were observed in Notopterus notopterus or Sperata seenghala. This study also concluded that the prevalence of parasites increased with increasing length, size, and age of fish.

Free radicals, mostly consist of reactive oxygen species, are generated in human body by several exogenous and endogenous systems. Overproduction of free radicals is known to cause several degenerative disorders including cancer. The aim of this study is to synthesize silver nanoparticles (AgNPs) using root extract of Reynoutria japonica and to investigate its antioxidant and cytotoxic potential. AgNPs were synthesized by green approach and subsequently characterized using UV–vis spectroscopy, SEM, TEM, FTIR, XRD, EDS and DLS. The antioxidant activity was investigated using DPPH, FRAP, H2O2, and ABTṠ+ radical scavenging assays while the cytotoxic effect was assessed using different human cancer cell lines including lung (A549), liver (Hep-G2) and breast (MDA-MB-231) by MTS assay. Moreover, the specificity of NPs was assessed against two normal human cell lines e.g. alveolar and renal primary epithelial cells (HPAEpiC and HRPTEpiC). The UV–vis spectra confirmed the synthesis of AgNPs by producing a characteristic peak at 410 nm. Further analysis confirmed that AgNPs were crystalline in nature, predominantly spherical in shape, with an average width and area of 17.34 nm and 164.46 nm2, respectively. DLS analysis revealed that NPs possess a high negative zeta potential value (−28.5 mV), thus facilitating its electrostatic stabilization. AgNPs showed dose dependent antioxidant activity against DPPH, FRAP, H2O2 and ABTS with IC50 values 19.25, 22.45, 24.20 and 18.88 µg/ml, respectively. The AgNPs depicted significant cytotoxic effects against A549, Hep-G2 and MDA-MB-231 cell lines with IC50 values of 4.5, 5.1 and 3.46 µg/ml, respectively. Moreover, the NPs exhibited highest selectivity index (>2.0) for A549, Hep-G2 and MDA-MB-231, confirming its specificity towards cancer cell lines. In conclusion, AgNPs prepared from root extract of R. japonica possess strong antioxidant and cytotoxic potential which suggests that they should be investigated further in order to develop safe and effective antioxidant and/or cytotoxic formulations.

BackgroundDecline in cardio-metabolic health, immunity, and physical activity is associated with old age. Old people also find it difficult to engage in structured exercise programs. Therefore, there is a need to investigate common daily chores as an alternative for exercise that may also help in maintaining cardio-metabolic and immune health.ObjectiveWe aimed to investigate whether Salat, an obligatory Islamic prayer involving various physical movements and closely resembling yoga, enhances the benefits conferred by the current guidelines for physical activity.MethodsA total of 30 overweight adults (mean (SD) age of 53.5 (8.7) years) participated in this study. For a 4-week duration, we compared the effects of Salat before/after meals (Pre-MS/Post-MS) on selected immunological and metabolic parameters in serum samples. We also compared the effects of both Pre-MS/Post-MS regimens in young and old subjects to observe any age-related effects.ResultsMost of the baseline metabolic parameters and the count of immune cells were normal. Post-MS resulted in a significant reduction in body weight and percent body fat (%BF). Overall, Post-MS resulted in a clear leukocytosis with a significant increase in granulocytes, monocytes, and lymphocytes. When analyzing the lymphocyte compartment, a clear numerical increase was noted for T, B, and NK cells. The number of CD8+ T cells showed a statistically significant increase. Similarly, Post-MS induced leukocytosis in both young and old individuals, while the increase in granulocytes, monocytes, and lymphocytes was statistically significant in old subjects only.ConclusionThis study demonstrated that the Islamic obligatory and congressional Salat practice is capable of mimicking desirable pro-immune and pro-metabolic health effects.Clinical trial registration(UMIN000048901).

Soil salinity is one of the significant abiotic threats to crops that deteriorates crop yields, and the world’s increasing population faces serious food problems due to abiotic threats. It is one of the major abiotic problems affecting more than 30% of irrigated land across the globe. The concentrations of various salts, such as NaCl, KCl, Na2SO4, and Na2CO3, cause saline stress; however, NaCl is the most abundant salt in the soil. Salinity could affect seed germination due to osmotic potential or due to specific toxic ion effects, and it decreases germination percentage and increases germination time, and high salt stress is responsible for delaying seed germination. Therefore, it is necessary to alleviate the negative impact of soil salinity during seedling growth periods, so the growth of crops in salt-affected soil will be much more enhanced. Seed priming is the utmost effective technique that could mitigate the harmful impact of soil salinity. This methodology not only minimizes the salinity tolerance but also strengthens the defense system of crops. In this technique, the hydration level within the seeds is controlled by applying pre-sowing treatments, allowing specific pre-germinative metabolic processes to occur and preventing radical emergence. Seed priming also decreases the seed germination time and improves antioxidant enzyme activities, stopping or minimizing reactive oxygen species’ adverse effects. It enhances the seedling performance with rapid and homogenous germination and vigorous and dynamic growth of the seedling, achieving a physiological situation leading to quick and enhanced emergence and germination of various crops. This review covers the mechanisms of seed priming, salinity tolerance, seed priming crosstalk with salinity tolerance, and seed priming techniques that induce biochemical, physiological, and morphological mechanisms in saline stress. Further research needs to be performed on advanced seed priming methods such as priming with nanoparticles and seed priming with physical agents (UV radiation, X-rays, gamma rays, and microwaves) to minimize the negative impact of salinity stress on different crops under different harsh environmental conditions.

Abstract Medicinal plants are highly used in the ethnoveterinary practice as considerable livestock resources in remote areas. The aim of the present study is to explore the ethnoveterinary medicinal practices in three different communities and discuss the cross‐cultural consensus on the usage of medicinal plants for the treatment of animals. The field survey was conducted by the animal healers of the area during the different seasons of plant growth. A total of 83 informants were interviewed through Semi‐structured interview involving experts of traditional knowledge in 21 localities of the three regions (Zhob, D. I. Khan and Mianwali) were conducted. Findings of the study were quantitatively analyzed through the informant consensus factors to identify the homogeneity information provided by the informants. Furthermore, cross‐culture consensuses were analyzed and recorded data were represented in a tabulated and Venn diagrams. In particularly, 59 species of plants were documented in the comparative analysis. Among them, 32 plant species were recorded in Pashto community, while Punjabi and Sarakai communities exhibited nine and four plant species, respectively. Whereas cross‐cultural analysis showed 14 medicinal plants that were commonly utilized by three different ethnic communities, that indicated low interregional consensus in regard to ethnoveterinary practices of medicinal plants. The current study showed that different communities and ethnic groups sharing some traditional knowledge and cross‐culturally approaches have been reported from traditional uses of plants against livestock's diseases. Therefore, current findings are the opportunities to scrutinize the plants for the discovery of new drug sources for humans and animals.

Abstract Background In order to find a new natural resource for pain-relief, the analgesic effects of Ilex dipyrena crude extract, fractions, and subfractions were evaluated in in-vivo mouse models with possible mechanism of action. Methods Analgesic effects of crude extract (100 and 200 mg/kg body weight), fractions and subfractions (75 mg/kg body weight) were screened using heat-induced (tail-immersion and hot plate test) and chemical-induced (formalin and acetic acid) nociception models in mice. The samples were also tested for the elucidation of a possible mechanism through opioidergic and GABAergic systems. Results The administration of crude extract, fractions and subfractions produced analgesic responses in acetic acid, formalin, tail immersion, and hot plate model for pain similar to those obtained with the standard. Naloxone antagonized the antinociceptive effects of the tested samples, whereas bicuculline showed partial inhibition. Considering the analgesic response, crude extract, fractions, and subfractions demonstrated promising inhibitory activity against all test models for pain, which was further supported by the possible involvement of opioidergic and GABAergic systems. Conclusion The results suggest that this plant may be useful in the development of new analgesic drugs. Further research with regard to the isolation of bioactive compounds is required to verify these findings.

Melatonin, an antioxidant hormone secreted by the pineal gland, has been recognized as a regulator for numerous biological events. The deleterious effects of juglone, a polyphenolic extract of walnut trees, on embryo development has been previously reported. In the current study, we aimed to display the impact of melatonin administrated during in vitro oocyte maturation (IVM) on juglone-treated oocytes. Thus, in vitro matured oocytes were collected after 24 h post incubation with juglone in the presence or absence of melatonin. Reactive oxygen species (ROS), glutathione (GSH) content, mitochondrial distribution, and the relative abundance of mRNA transcription levels were assessed in oocytes, in addition, oocytes were in vitro fertilized to check the competency levels of oocytes to generate embryos. We found that administration of melatonin during the maturation of oocytes under juglone stress significantly improved the cleavage rate, 8-16 cell-stage embryos and day-8 blastocysts when compared to the sole juglone treatment. In addition, the fluorescence intensity of ROS increased, whereas the GSH decreased in juglone-treated oocytes compared to melatonin–juglone co-treated and untreated ones. Additionally, a significant increase in the mitochondrial aberrant pattern, the pattern that was normalized following melatonin supplementation, was observed following juglone administration. The mRNA analysis using RT-qPCR revealed a significant upregulation of autophagy and oxidative-stress-specific markers in the juglone-treated group compared to the co-treatment and control. In conclusion, the study reveals, for the first time, a protective effect of melatonin against the oxidative stress initiated following juglone treatment during the in vitro maturation of oocytes.

Over the past decade, methicillin-resistant Staphylococcus aureus (MRSA) has become a major source of biofilm formation and a major contributor to antimicrobial resistance. The genes that govern biofilm formation are regulated by a signaling mechanism called the quorum-sensing system. There is a need for new molecules to treat the infections caused by dangerous pathogens like MRSA. The current study focused on an alternative approach using juglone derivatives from Reynoutria japonica as quorum quenchers. Ten bioactive compounds from this plant, i.e., 2-methoxy-6-acetyl-7-methyljuglone, emodin, emodin 8-o-b glucoside, polydatin, resveratrol, physcion, citreorosein, quercetin, hyperoside, and coumarin were taken as ligands and docked with accessory gene regulator proteins A, B, and C and the signal transduction protein TRAP. The best ligand was selected based on docking score, ADMET properties, and the Lipinski rule. Considering all these parameters, resveratrol displayed all required drug-like properties with a docking score of −8.9 against accessory gene regulator protein C. To further assess the effectiveness of resveratrol, it was compared with the commercially available antibiotic drug penicillin. A comparison of all drug-like characteristics showed that resveratrol was superior to penicillin in many aspects. Penicillin showed a binding affinity of −6.7 while resveratrol had a score of −8.9 during docking. This was followed by molecular dynamic simulations wherein inhibitors in complexes with target proteins showed stability inside the active site during the 100 ns simulations. Structural changes due to ligand movement inside the cavity were measured in the protein targets, but they remained static due to hydrogen bonds. The results showed acceptable pharmacokinetic properties for resveratrol as compared to penicillin. Thus, we concluded that resveratrol has protective effects against Staphylococcus aureus infections and that it suppresses the quorum-sensing ability of this bacterium by targeting its infectious proteins.

We have previously reported that juglone, a natural compound found in Juglandaceae with a wide range of biological activities, can reduces the developmental competence of bovine oocytes. In the current study, we investigated the possible mechanisms behind the toxicity of juglone and the relationship with PI3K/AKT/mTOR signaling during the in vitro maturation (IVM) of oocytes. Results show that oocyte exposure to juglone was associated with a significant decrease in filamentous actin (F-actin) accumulation. The RT-qPCR showed downregulation of the meiosis progression indicator GSK-3A, oocyte development marker BMP15, mitochondria fusion controlling MFN1, oxidative stress-related OGG1, and histone methylation-related EZH1, EZH2, SUZ12, G9a, and SUV39H2 genes in juglone-treated oocytes. In addition, glycolysis- (PFK1 and GLUT1), ATP synthesis- (ATPase8 and ATP5F1B), and OXPHOS-specific markers (SDHA and SDHD), as well as the oocyte survival regulators (SOD2, VEGF, and MAPK1) significantly decreased upon juglone treatment. Moreover, lower expression of PI3K, AKT, and mTOR was observed at the transcriptional and/or translational level(s). The autophagy markers LC3B and beclin-1 as well as the DNA damage-specific marker 8-OxoG displayed overexpression in juglone-exposed oocytes. Taken together, our results show that administration of juglone during the IVM can reduce the quality and developmental health of bovine oocytes through downregulation of the PI3K/AKT/mTOR pathway and its downstream signaling cascades.

Over the last decade, the education system has seen significant technical and architectural transformations after the COVID-19 epidemic. Additionally, it affects the innovative work performance and energy levels of teachers. This research examines the impact of idiosyncratic deals on the innovative work performance of university instructors in Pakistan. The attitude towards performing well serves as a mediator between innovative work performance and I-deals. In addition, cognitive dissonance has also served as a mediator between innovative work performance and ideals. Data for the current research were gathered from a sample of 392 university professors for further analysis and interpretation. The findings suggest that idiosyncratic deals substantially impact instructors' innovative work performance. Cognitive dissonance has a largely detrimental impact on idiosyncratic deals and the effectiveness of teachers' innovative work performance. Furthermore, a positive attitude towards performing well has a partial impact on teachers' idiosyncratic and innovative work performance. Cognitive theory advocates for examining methods to enhance teachers' positive energy throughout the execution of their duties. This research provides valuable insights for academic institutions and policy leaders in Pakistan's education sector. [ABSTRACT FROM AUTHOR]

We theoretically demonstrated a class of plasmonic coupled elliptical nanostructure for achieving a spaser or a nanolaser with high intensity. The plasmonic ellipse is made up of gold film substrate. The proposed structure is then trialed for various light polarizations, moreover, a simple elliptical nanostructure has been chosen primarily from which different cases have been formed by geometry alteration. The structure supports strong coupled resonance mode i.e. localized surface plasmon (LSP). The localized surface plasmon resonance (LSPR) of the investigated system is numerically examined using the finite-element method (FEM). The calculations showed that the LSPR peaks and the local field intensity or near field enhancement (NFE) of the active nanosystem can be amplified to higher values by introducing symmetry-breaking techniques in the proposed ellipse and its variants. The coupled nanostructure having different stages of wavelengths can be excited with different plasmonic resonance modes by the selection of suitable gain media. In addition, a small-sized nanolaser with high tunability range can be developed using this nanostructure. The spaser phenomena are achieved at several wavelengths by changing light polarization and structure alteration methods. Giant localized field enhancement and high LSPR values enable the proposed model to be highly appealing for sensing applications, surface-enhanced Raman spectroscopy, and much more.

Resistance to antimicrobial agents are rendering therapies ineffective around the globe, leading to increased mortality and treatment cost. Likewise, non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics possess several side effects particularly peptic ulcer and gastrointestinal problems. Metallic nanoparticles significantly enhances the therapeutic efficacy of natural extracts owing to improved bioavailability thereby lowering the dose and side effects. The purpose of this research was to investigate the efficacy of gold nanoparticles (AuNPs). In this study, Sambucus wightiana whole plant aqueous extract was used for rapid and eco-friendly synthesis of AuNPs. They were characterized by various analytical techniques including UV–Visible spectroscopy (UV–Vis), transmission and scanning electron microscopy (TEM and SEM), energy dispersive X-ray spectroscopy (EDX), Zetasizer, X-ray diffractometer (XRD) and Fourier transform infra-red spectroscopy (FTIR). The UV–Vis spectra revealed a distinct absorption peak at 539 nm; TEM and SEM images confirmed the formation of heterogeneously dispersed AuNPs with an average area of 152.77 nm2 and width of 15.96 nm. The AuNPs showed significant inhibitory zones against Escherichia coli (25 mm), Staphylococcus epidermis (23 mm) and Salmonella enteritidis (18 mm) with MIC values 0.13, 0.11 and 0.16 mg/ml, respectively. Among fungal strains it showed highest percent inhibition against Fusarium solani (90%) and Microsporum canis (80%) with MIC values 0.02 and 0.01 mg/ml, respectively. It showed maximum anti-inflammatory activity (43.70, 48.80 and 57.08%) at 20 mg/kg dose at both early and late hours of inflammation. Likewise, in vitro models depicted concentration dependent inhibition of 5-LOX and COX-2 enzymes. AuNPs showed highest antioxidant activity (68.7% inhibition) at 1000 µg/ml, compared to ascorbic acid that showed 77.8% inhibition at the same concentration. Similarly, it exhibited significant (P ≤ 0.001) dose dependent analgesic effect with maximum inhibition (56.22%) at 20 mg/kg. In conclusion, the above findings suggest that AuNPs should be studied further in order to develop safe and effective formulations.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection can trigger the adaptive and innate immune responses, leading to uncontrolled inflammatory reactions and associated local and systematic tissue damage, along with thromboembolic disorders that may increase the risk of acute ischemic stroke (AIS) in COVID-19 patients. The neuropilin (NRP-1) which is a co-receptor for the vascular endothelial growth factor (VEGF), integrins, and plexins, is involved in the pathogenesis of AIS. NRP-1 is also regarded as a co-receptor for the entry of SARS-CoV-2 and facilitates its entry into the brain through the olfactory epithelium. NRP-1 is regarded as a cofactor for binding of SARS-CoV-2 with angiotensin-converting enzyme 2 (ACE2), since the absence of ACE2 reduces SARS-CoV-2 infectivity even in presence of NRP-1. Therefore, the aim of the present study was to clarify the potential role of NRP-1 in COVID-19 patients with AIS. SARS-CoV-2 may transmit to the brain through NRP-1 in the olfactory epithelium of the nasal cavity, leading to different neurological disorders, and therefore about 45% of COVID-19 patients had neurological manifestations. NRP-1 has the potential capability to attenuate neuroinflammation, blood–brain barrier (BBB) permeability, cerebral endothelial dysfunction (ED), and neuronal dysfunction that are uncommon in COVID-19 with neurological involvement, including AIS. Similarly, high NRP-1 serum level is linked with ED, oxidative stress, and the risk of pulmonary thrombosis in patients with severe COVID-19, suggesting a compensatory mechanism to overcome immuno-inflammatory disorders. In conclusion, NRP-1 has an important role in the pathogenesis of COVID-19 and AIS, and could be the potential biomarker linking the development of AIS in COVID-19. The present findings cannot provide a final conclusion, and thus in silico, experimental, in vitro, in vivo, preclinical, and clinical studies are recommended to confirm the potential role of NRP-1 in COVID-19, and to elucidate the pharmacological role of NRP-1 receptor agonists and antagonists in COVID-19.

Background and objectives: COVID-19 patients exhibit a broad range of manifestations, presenting with a flu-like respiratory tract infection that can advance to a systemic and severe disease characterized by pneumonia, pulmonary edema, severe damage to the airways, and acute respiratory distress syndrome (ARDS, causing fatality in 70% of COVID-19 cases). A ‘cytokine storm’ profile is found in most severely influenced COVID-19 patients. The treatment protocol of the disease also includes tocilizumab, which is a humanized monoclonal antibody used to treat autoimmune and inflammatory conditions. This study was designed (1) to assess the role of tocilizumab in COVID-19 patients regarding therapeutic efficacy through evaluation of cytokine release syndrome (CRS) resolution and anticoagulant effect, analyzing clinical safety via monitoring of associated adverse effects profile; and (2) to compare the clinical safety and therapeutic efficacy of institutional treatment regimen (alone) versus tocilizumab added to an institutional treatment module in COVID-19 patients. Materials and Methods: In this study, the endpoints parametric assessment of severely diseased patients of COVID-19 was performed (total n = 172, control group (institutional protocol treatment provided), n = 101 and test group (tocilizumab provided), n = 71) at the Khyber Teaching Institution, MTI, Peshawar. The assessments were compared using non-parametric analyses at baseline and after a follow-up of 12–18 days until the patient discharged or expired. Results: Results of the study revealed an insignificant difference among the control vs. test group in resolving inflammatory parameters (C-reactive protein (CRP) 21.30 vs. 50.07; p = 0.470, ferritin 482.9 vs. 211.5; p = 0.612, lactate dehydrogenase (LDH) 29.12 vs.18.8; p = 0.0863, and D-dimer 464 vs.164.4; p = 0.131). However, a statistically significant difference was found between the control group and test group regarding coagulation parameters (international normalized ratio (INR) 0.12 vs. −0.07; p ≤ 0.001; activated partial thromboplastin time (aPTT) 0.42 vs. −1.16; p ≤ 0.001; prothrombin time (PT) 0.31 vs. −0.96; p ≤ 0.001; platelet count −12.34 vs. −1.47; p = 0.012) and clinical survival rate (89.10 vs. 90.14; p < 0.001). Furthermore, there was significantly higher infection rates and raised alanine aminotransferase (ALT) and alkaline phosphatase (ALP) associated with the tocilizumab group as compared to those receiving institutional treatment (bacterial infections: 0.99% vs. 15.49%; p ≤ 0.01, ALT: 3.96% vs. 28.16%; p ≤ 0.01, ALP: 1.98% vs. 22.53%; p ≤ 0.01). Conclusions: From this study, it was concluded that tocilizumab can be a better drug of choice in terms of efficacy, particularly in resolving coagulopathy in severe COVID-19 patients.