The main protease of SARS-CoV-2 cleaves histone deacetylases and DCP1A, attenuating the immune defense of the interferon-stimulated genes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019, constitutes an emerging human pathogen of zoonotic origin. A critical role in protecting the host against invading pathogens is carried out by interferon-stimulated genes (ISGs), the primary effectors of the type I interferon (IFN) response. All coronaviruses studied thus far have to first overcome the inhibitory effects of the IFN/ISG system before establishing efficient viral replication. However, whether SARS-CoV-2 evades IFN antiviral immunity by manipulating ISG activation remains to be elucidated. Here, we show that the SARS-CoV-2 main protease (Mpro) significantly suppresses the expression and transcription of downstream ISGs driven by IFN-stimulated response elements in a dose-dependent manner, and similar negative regulations were observed in two mammalian epithelial cell lines (simian Vero E6 and human A549). Our analysis shows that to inhibit the ISG production, Mpro cleaves histone deacetylases (HDACs) rather than directly targeting IFN signal transducers. Interestingly, Mpro also abolishes the activity of ISG effector mRNA-decapping enzyme 1a (DCP1A) by cleaving it at residue Q343. In addition, Mpro from different genera of coronaviruses has the protease activity to cleave both HDAC2 and DCP1A, even though the alphacoronaviruse Mpro exhibits weaker catalytic activity in cleaving HDAC2. In conclusion, our findings clearly demonstrate that SARS-CoV-2 Mpro constitutes a critical anti-immune effector that modulates the IFN/ISG system at multiple levels, thus providing a novel molecular explanation for viral immune evasion and allowing for new therapeutic approaches against coronavirus disease 2019 infection.

Thyroid status in pregnancy: Comparison of thyroid function abnormalities in women with and without a history of miscarriage or stillbirth.

Objective: To evaluate thyroid function tests (TFTs) during pregnancy in women with previous history of miscarriage or stillbirth. Methods: A cross-sectional study was carried out at the department of Obstetrics & Gynaecology and Endocrinology, Lady Reading Hospital, Peshawar from February 2021 to March 2022. All multigravida women attending the antenatal clinics were included using consecutive sampling. These women were placed into two groups, Group-A comprised of women with no prior history of miscarriages or stillbirths, and those with a history of foetal death during previous pregnancies were assigned Group-B. Free T4, thyroid stimulating hormone (TSH) and anti-thyroid peroxidase (TPO) antibodies were measured and the former two were used to label patients with thyroid dysfunction. Results: A total of 139 multigravida women were included in the study. About 43% of the women had a history of miscarriages or stillbirths. Thyroid dysfunction was observed overall in 36.69 % women, of whom 25.18% had sub-clinical hypothyroidism, 6.47% had hypothyroidism and 5.04 % were sub-clinical hyperthyroid. Women in Group-B had more thyroid functions abnormalities compared to Group-A (p<0.05). Moreover, there was significant difference in median TSH and freeT4 between the groups (p<0.001). Overall, thyroid dysfunction was found in 66.67% of patients who had a history of foetal death. Conclusions: In pregnant women with a history of miscarriage or abortion, thyroid functions abnormalities are common therefore routine thyroid testing is advised in pregnant women to prevent adverse perinatal outcomes.

Construction of Genetically Encoded Biosensors to Monitor Subcellular Compartment-Specific Glutathione Response to Chemotherapeutic Drugs in Acute Myeloid Leukemia Cells.

Glutathione (GSH), the constituent of the redox buffer system, is a scavenger of reactive oxygen species (ROS), and its ratio to oxidized glutathione (GSSG) is a key indicator of oxidative stress in the cell. Acute myeloid leukemia (AML) is a highly aggressive hematopoietic malignancy characterized by aberrant levels of reduced and oxidized GSH due to oxidative stress. Therefore, the real-time, dynamic, and highly sensitive detection of GSH/GSSG in AML cells is of great interest for the clinical diagnosis and treatment of leukemia. The application of genetically encoded sensors to monitor GSH/GSSG levels in AML cells is not explored, and the underlying mechanism of how the drugs affect GSH/GSSG dynamics remains unclear. In this study, we developed subcellular compartment-specific sensors to monitor GSH/GSSG combined with high-resolution fluorescence microscopy that provides insights into basal GSH/GSSG levels in the cytosol, mitochondria, nucleus, and endoplasmic reticulum of AML cells, in a decreasing order, revealing substantial heterogeneity of GSH/GSSG level dynamics in different subcellular compartments. Further, we investigated the response of GSH/GSSG ratio in AML cells caused by Prussian blue and Fe3O4 nanoparticles, separately and in combination with cytarabine, pointing to steep gradients. Moreover, cytarabine and doxorubicin downregulated the GSH/GSSG levels in different subcellular compartments. Similarly, live-cell imaging showed a compartment-specific decrease in response to various drugs, such as CB-839, parthenolide (PTL), and piperlongumine (PLM). The enzymatic activity assay revealed the mechanism underlying fluctuations in GSH/GSSG levels in different subcellular compartments mediated by these drugs in the GSH metabolic pathway, suggesting some potential therapeutic targets in AML cells.

Concomitant Effect of Quercetin and Its Copper Complex in the Development of Sustained-Release Nanoparticles of Polycaprolactone, Used for the Treatment of Skin Infection.

The study aimed to improve the treatment of impetigo with naturally occurring quercetin and its copper-quercetin (Cu-Q) complex by preparing sustained-release (SR) nanoparticles of polycaprolactone (PCL). The solvent evaporation method was used for the copper-quercetin (Cu-Q) complex formation, and their PCL nanoparticles (PCL-NPs, Q-PCL-NPs, and Cu-Q-PCL-NPs) were prepared by the high-pressure homogenization method. Synthesis of nanoparticles was confirmed by their physicochemical and antibacterial properties of quercetin against Gram-positive as well as Gram-negative bacteria. The percentage loading efficiency of quercetin and release in 100 mM of phosphate buffer pH 7.4 and 5.5 at 37 °C was found to be more than 90% after 24 h with the zero-order release pattern. Minimum inhibitory concentration of nanoparticles was found to increase threefold in the case of Cu-Q-PCL-NPs may be due to the synergistic antibacterial behavior. Scanning electron microscopy showed spherical nanoparticles, and surface roughness was confirmed by atomic force microscopy analysis. Fortunately, no sign of irritation on rat skin even at 3%, was seen. In vitro antioxidant assay by 2,2-diphenyl-1-picrylhydrazyl reduction was found to be ≤80 ± 0.02% which confirmed their scavenging activity. Interestingly, for the ex vivo study, the tape-stripping model was applied against Staphylococcus aureus containing rats and showed the formation of the epidermal layer within 4-5 days. Confirmation of antibacterial activity of pure quercetin, from Cu-Q complex, and their SR release from Q-PCL-NPs and Cu-Q-PCL-NPs was considered an effective tool for the treatment of skin diseases and can be used as an alternative of already resistant ciprofloxacin in impetigo.

An Innovative Clustering Hierarchical Protocol for Data Collection from Remote Wireless Sensor Networks Based Internet of Things Applications.

Recently, unmanned aerial vehicles (UAVs) have emerged as a viable solution for data collection from remote Internet of Things (IoT) applications. However, the successful implementation in this regard necessitates the development of a reliable and energy-efficient routing protocol. This paper proposes a reliable and an energy-efficient UAV-assisted clustering hierarchical (EEUCH) protocol designed for remote wireless sensor networks (WSNs) based IoT applications. The proposed EEUCH routing protocol facilitates UAVs to collect data from ground sensor nodes (SNs) that are equipped with wake-up radios (WuRs) and deployed remotely from the base station (BS) in the field of interest (FoI). During each round of the EEUCH protocol, the UAVs arrive at the predefined hovering positions at the FoI, perform clear channel assignment, and broadcast wake-up calls (WuCs) to the SNs. Upon receiving the WuCs by the SNs' wake-up receivers, the SNs perform carrier sense multiple access/collision avoidance before sending joining requests to ensure reliability and cluster-memberships with the particular UAV whose WuC is received. The cluster-member SNs turn on their main radios (MRs) for data packet transmission. The UAV assigns time division multiple access (TDMA) slots to each of its cluster-member SNs whose joining request is received. Each SN must send the data packets in its assigned TDMA slot. When data packets are successfully received by the UAV, it sends acknowledgments to the SNs, after which the SNs turn off their MRs, completing a single round of the protocol. The proposed EEUCH routing protocol with WuR eliminates the issue of cluster overlapping, improves the overall performance, and increases network stability time by a factor of 8.7. It also improves energy efficiency by a factor of 12.55, resulting in a longer network lifespan compared to Low Energy Adaptive Clustering Hierarchy (LEACH) protocol. Moreover, EEUCH collects 5.05 times more data from the FoI than LEACH. These results are based on simulations in which the EEUCH protocol outperformed the existing six benchmark routing protocols proposed for homogeneous, two-tier, and three-tier heterogeneous WSNs.

A Deep Recurrent Learning-Based Region-Focused Feature Detection for Enhanced Target Detection in Multi-Object Media.

Target detection in high-contrast, multi-object images and movies is challenging. This difficulty results from different areas and objects/people having varying pixel distributions, contrast, and intensity properties. This work introduces a new region-focused feature detection (RFD) method to tackle this problem and improve target detection accuracy. The RFD method divides the input image into several smaller ones so that as much of the image as possible is processed. Each of these zones has its own contrast and intensity attributes computed. Deep recurrent learning is then used to iteratively extract these features using a similarity measure from training inputs corresponding to various regions. The target can be located by combining features from many locations that overlap. The recognized target is compared to the inputs used during training, with the help of contrast and intensity attributes, to increase accuracy. The feature distribution across regions is also used for repeated training of the learning paradigm. This method efficiently lowers false rates during region selection and pattern matching with numerous extraction instances. Therefore, the suggested method provides greater accuracy by singling out distinct regions and filtering out misleading rate-generating features. The accuracy, similarity index, false rate, extraction ratio, processing time, and others are used to assess the effectiveness of the proposed approach. The proposed RFD improves the similarity index by 10.69%, extraction ratio by 9.04%, and precision by 13.27%. The false rate and processing time are reduced by 7.78% and 9.19%, respectively.

Fabrication, Characterization and Biomedical Evaluation of a Statistically Optimized Gelatin Scaffold Enriched with Co-Drugs Loaded into Controlled-Release Silica Nanoparticles.

The current study focused on the fabrication of a well-designed, biocompatible, physically stable, non-irritating and highly porous gelatin scaffold loaded with controlled-release triamcinolone acetonide (TA) and econazole nitrate (EN) co-loaded into mesoporous silica nanoparticles (EN-TA-loaded MSNs) to provide a better long-lasting antifungal therapeutic effect with minimal unfavorable effects. Optimization of the MSNs-loaded scaffold was performed using central composite rotatable design (CCRD), where the effect of gelatin concentration (X1), plasticizer (X2) and freezing time (X3) on the entrapment of EN (Y1) and TA (Y2) and on the release of EN (Y3) and TA (Y4) from the scaffold were studied. The significant compatibility of all formulation ingredients with both drugs was established from XRD, DSC and FT-IR spectra analyses while SEM and zeta studies represented a very precise unvarying distribution of the loaded MSNs in the porous structure of the scaffold. The stability of the optimized scaffold was confirmed from zeta potential analysis (-16.20 mV), and it exhibited higher entrapment efficiency (94%) and the slower (34%) release of both drugs. During in vitro and in vivo antifungal studies against Candida albicans, the MSNs-loaded scaffold was comparatively superior in the eradication of fungal infections as a greater zone of inhibition was observed for the optimized scaffold (16.91 mm) as compared to the pure drugs suspension (14.10 mm). Similarly, the MSNs-loaded scaffold showed a decreased cytotoxicity because the cell survival rate in the scaffold presence was 89% while the cell survival rate was 85% in the case of the pure drugs, and the MSNs-loaded scaffold did not indicate any grade of erythema on the skin in comparison to the pure medicinal agents. Conclusively, the scaffold-loaded nanoparticles containing the combined therapy appear to possess a strong prospective for enhancing patients' adherence and therapy tolerance by yielding improved synergistic antifungal efficacy at a low dose with abridged toxicity and augmented wound-healing impact.

Assessment of lithium bioaccumulation by quinoa (Chenopodium quinoa willd.) and its implication for human health.

Lithium (Li) is the lightest alkali metal and 27th most abundant element in the earth crust. In traces, the element has medicinal value for various disorders in humans, however, its higher concentrations may lead to treatment-resistant depression and altered thyroid functioning. Quinoa (Chenopodium quinoa) has gained popularity owing to its halophytic nature and its potential use as an alternative to the traditional staple foods. However, quinoa response to Li-salt in terms of growth, Li accumulation potential and health risks associated with consumption of the quinoa seeds grown on Li-contaminated soils has not been explored yet. During this study, quinoa was exposed to various concentrations of Li (0, 2, 4, 8 and 16 mM) at germination as well as seedling stages. The results showed that seed germination was the highest (64% higher than control) at Li concentration of 8 mM. Similarly, at 8 mM doses of Li shoot length, shoot dry weight, root length, root dry weight and grain yield were increased by 130%, 300%, 244%, 858% and 185% than control. It was also revealed that Li increased the accumulation of calcium and sodium in quinoa shoots. Carotenoids contents were increased, but chlorophyll contents remained un-changed under Li application. The activities of antioxidants viz. Peroxide dismutase, catalase and super oxide dismutase were also increased with an increase in the levels of Li in the soil. Estimated daily intake and hazard quotient of Li in quinoa were less than the threshold level. It was concluded that Li concentration of 8 mM is useful for quinoa growth and it can be successfully grown on Li contaminated soils without causing any human health risks.

Salinity mitigates cadmium-induced phytotoxicity in quinoa (Chenopodium quinoa Willd.) by limiting the Cd uptake and improved responses to oxidative stress: implications for phytoremediation.

Cadmium (Cd) contamination and soil salinity are the main environmental issues reducing crop productivity. This study aimed to examine the combined effects of salinity (NaCl) and Cd on the physiological and biochemical attributes of quinoa (Chenopodium quinoa Willd.). For this purpose, 30-day-old plants of quinoa genotype "Puno" were transplanted in Hoagland's nutrient solution containing diverse concentrations of Cd: 0, 50, 100, 200 µM Cd, and salinity: 0, 150, and 300 mM NaCl. Results demonstrated that plant growth, stomatal conductance, and pigment contents were significantly lower at all Cd concentrations than the control plants. Quinoa plants exhibited improved growth and tolerance against Cd when grown at a lower level of salinity (150 mM NaCl) combined with Cd. In contrast, the elevated concentration of salinity (300 mM NaCl) combined with Cd reduced shoot and root growth of experimental plants more than 50%. Combined application of salinity and Cd increased Na (25-fold), while lessened the Cd (twofold) and K (1.5-fold) uptake. A blend of high concentrations of Na and Cd caused overproduction of H2O2 (eightfold higher than control) contents and triggered lipid peroxidation. The activities of antioxidant enzymes: ascorbate peroxidase (APX), catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) were 13, 12, 7 and ninefold higher than control to mitigate the oxidative stress. Due to restricted root to shoot translocation, and greater tolerance potential against Cd, the quinoa genotype, Puno, is suitable for phytostabilization of Cd in saline soils.

Nickel toxicity pretreatment attenuates salt stress by activating antioxidative system and ion homeostasis in tomato (Solanum lycopersicon L.): an interplay from mild to severe stress.

Plants antioxidative system is the first line of defense against oxidative stress caused secondarily by toxic ions under salinity. Plants with pre-activated antioxidative system can better adapt to salinity and can result in higher growth and yield. The current experiment was conducted to assess the adaptation of two tomato genotypes (Riogrande and Green Gold) with pre-activated antioxidative enzymes against salt stress. Tomato seedlings were exposed to mild stress (Ni: 0, 15 and 30 mg L-1) for three weeks to activate the antioxidative enzymes. The seedlings with pre-activated antioxidative enzymes were then grown under severe stress in hydroponics (0, 75 and 150 mM NaCl) and soil (control, 7.5 and 15 dS m-1) to check the adaptation, growth and yield. The results showed that Ni toxicity significantly enhanced activities of antioxidant enzymes (SOD, CAT, APX and POX) in both the genotypes and reduced growth with higher values in genotype Riogrande than Green Gold. The seedlings with pre-activated antioxidant enzymes showed better growth, low Na+ and high K+ uptake and maintained higher antioxidative enzymes activity than non-treated seedlings after four weeks of salt stress treatment in hydroponics. Similarly, the results in soil salinity treatment of the Ni pretreated seedlings showed higher yield characteristics (fruit yield per plant, average fruit weight and fruit diameter) than non-treated seedlings. However, Ni pretreatment had nonsignificant effect on tomato fruit quality characteristics like fruit dry matter percentage, total soluble solids, fruit juice pH and titratable acidity. The genotype Riogrande showed better growth, yield and fruit quality than Green Gold due to higher activity of antioxidant enzymes and better ion homeostasis as a result of Ni pretreatment. The results suggest that pre-activation antioxidant enzymes by Ni treatment proved to be an effective strategy to attenuate salt stress for better growth and yield of tomato plants.

Risk assessment of trace element accumulation in soil and Brassica oleracea after wastewater irrigation.

The risk assessment of trace elements has received substantial attention for the achievement of UN Sustainable Developmental Goals (UN-SDGs). The present study aimed to evaluate health and ecological risks associated with trace element accumulation in Brassica oleracea under wastewater irrigations from three different areas. This study, for the first time, compared the pros and cons of mixed water crop irrigation (wastewater with fresh/groundwater). A pot experiment was conducted to evaluate the buildup of eight trace elements (As, Cu, Cd, Mn, Fe, Pb, Ni and Zn) in soil and B. oleracea plants irrigated with wastewater alone and mixed with fresh/groundwater. Specific ecological [degree of contamination (Cd), potential ecological risk index (PERI), pollution load index (PLI), geo-accumulation index (Igeo)], phytoaccumulation [bioconcentration factor (BCF) and transfer factor (TF)] and health risk models [chronic daily intake (CDI), hazard quotient (HQ), cancer risk (CR)] were applied to assess the overall contamination of trace elements in the soil-plant-human system. Moreover, these indices were compared with the literature data. The concentration of Cd, Fe and Mn exceeded the threshold limits of 10, 500 and 200 mg kg-1, respectively, for agricultural soil. Overall, all the irrigation waters caused significant pollution load in soil indicating high ecological risk (Cd > 24, PERI > 380, Igeo > 5, PLI > 2). Not all the mixing treatments caused a reduction in trace element buildup in soil. The mixing of wastewater-1 with either groundwater or freshwater increased trace element levels in the soil as well as risk indices compared to wastewater alone. The BCF and TF values were > 1, respectively, for 66% and 7% treatments. Trace element concentration in plants and associated health risk were minimized in mixed wastewater treatments. There were 22% and 32% reduction in HQ and CR when wastewater was mixed with freshwater and 29% and 8% when mixed with groundwater. Despite total reduction, a great variation in % change in risk indices was observed with respect to the area of wastewater collection. Therefore, mixed water irrigation may be a good management strategy, but its recommendation depends on soil properties and composition of waters used for mixing. Moreover, it is recommended that the freshwater and wastewater of the particular area may be continuously monitored to avoid potential associated health hazards.

Chromium removal from aqueous solution using bimetallic Bi0/Cu0-based nanocomposite biochar.

Chromium (Cr), due to its greater contamination in aquifers and distinct eco-toxic impacts, is of greater environmental concern. This study aimed to synthesize nanocomposites of almond shells biochar (BC) with zerovalent bismuth and/or copper (Bi0/BC, Cu0/BC, and Bi0-Cu0/BC) for the removal of Cr from aqueous solution. The synthesized nanocomposites were investigated using various characterization techniques such as XRD, FTIR spectroscopy, SEM, and EDX. The Cr removal potential by the nanocomposites was explored under different Cr concentrations (25-100 mg/L), adsorbent doses (0.5-2.0 g/L), solution pH (2-8), and contact time (10-160 min). The above-mentioned advanced techniques verified successful formation of Bi0/Cu0 and their composite with BC. The synthesized nanocomposites were highly effective in the removal of Cr. The Bi0-Cu0/BC nano-biocomposites showed higher Cr removal efficiency (92%) compared to Cu0/BC (85%), Bi0/BC (76%), and BC (67%). The prepared nanocomposites led to effective Cr removal at lower Cr concentrations (25 mg/L) and acidic pH (4.0). The Cr solubility changes with pH, resulting in different degrees of Cr removal by Bi0-Cu0/BC, with Cr(VI) being more soluble and easier to adsorb at low pH levels and Cr(III) being less soluble and more difficult to adsorb at high pH levels. The experimental Cr adsorption well fitted with the Freundlich adsorption isotherm model (R2 > 0.99) and pseudo-second-order kinetic model. Among the prepared nanocomposites, the Bi0-Cu0/BC showed greater stability and reusability. It was established that the as-synthesized Bi0-Cu0/BC nano-biocomposite showed excellent adsorption potential for practical Cr removal from contaminated water.

Two-Dimensional Protein Nanoarray as a Carrier of Sensing Elements for Gold-Based Immunosensing Systems.

Homogeneous and high-density immobilization of proteins on gold-based sensing surface without the loss of protein activity is of great significance for high-performance immunosensing but remains challenging. To realize more sensitive immunosensing, an improved method for protein immobilization on the gold surface is urgently required. Here, we propose a biological and mild approach by combining a genetically encoded SpyTag-SpyCatcher interaction system with a redesigned S-layer of bacteria. This method allows proteins of interest to be covalently linked with the S-layer in a biological manner and arranged orderly in a two-dimensional nanoarray on the gold surface. The activity of African swine fever virus proteins was significantly preserved after immobilization. In addition, our S-layer-based immobilization method exhibited an eightfold increase in detection sensitivity compared with the conventional chemical cross-linking for protein immobilization during serological tests. Together, our S-layer-based immobilization method provides an innovative approach for building a quality gold-based biosensing interface and should greatly contribute to the high-sensitivity sensing for a deeper understanding of pathogen infection and host immunity.

Interstitial lung abnormalities and interstitial lung diseases associated with cigarette smoking in a rural cohort undergoing surgical resection.

BACKGROUND: Cigarette smoking is a risk factor for interstitial lung abnormalities (ILAs) and interstitial lung diseases (ILDs). Investigation defining the relationships between ILAs/ILDs and clinical, radiographic, and pathologic findings in smokers have been incomplete. Employing a cohort undergoing surgical resection for lung nodules/masses, we (1) define the prevalence of ILAs/ILDs, (2) delineate their clinical, radiographic and pathologic predictors, and (3) determine their associations with mortality. METHODS: Patients undergoing resection of lung nodules/masses between 2017 and 2020 at a rural Appalachian, tertiary medical center were retrospectively investigated. Predictors for ILAs/ILDs and mortality were assessed using multivariate logistic regression analysis. RESULTS: In the total study cohort of 352 patients, radiographic ILAs and ILDs were observed in 35.2% and 17.6%, respectively. Among ILA patterns, subpleural reticular changes (14.8%), non-emphysematous cysts, centrilobular (CL) ground glass opacities (GGOs) (8% each), and mixed CL-GGO and subpleural reticular changes (7.4%) were common. ILD patterns included combined pulmonary fibrosis emphysema (CPFE) (3.1%), respiratory bronchiolitis (RB)-ILD (3.1%), organizing pneumonitis (2.8%) and unclassifiable (4.8%). The group with radiographic ILAs/ILDs had a significantly higher proportion of ever smokers (49% vs. 39.9%), pack years of smoking (44.57 ± 36.21 vs. 34.96 ± 26.22), clinical comorbidities of COPD (35% vs. 26.5%) and mildly reduced diffusion capacity (% predicated 66.29 ± 20.55 vs. 71.84 ± 23). Radiographic centrilobular and paraseptal emphysema (40% vs. 22.2% and 17.6% vs. 9.6%, respectively) and isolated traction bronchiectasis (10.2% vs. 4.2%) were associated with ILAs/ILDs. Pathological variables of emphysema (34.9% vs. 18.5%), any fibrosis (15.9% vs. 4.6%), peribronchiolar metaplasia (PBM, 8% vs. 1.1%), RB (10.3% vs. 2.5%), and anthracosis (21.6% vs. 14.5%) were associated with ILAs/ILDs. Histologic emphysema showed positive correlations with any fibrosis, RB, anthracosis and ≥ 30 pack year of smoking. The group with ILAs/ILDs had significantly higher mortality (9.1% vs. 2.2%, OR 4.13, [95% CI of 1.84-9.25]). CONCLUSIONS: In a rural cohort undergoing surgical resection, radiographic subclinical ILAs/ILDs patterns were highly prevalent and associated with ever smoking and intensity of smoking. The presence of radiographic ILA/ILD patterns and isolated honeycomb changes were associated with increased mortality. Subclinical ILAs/ILDs and histologic fibrosis correlated with clinical COPD as well as radiographic and pathologic emphysema emphasizing the co-existence of these pulmonary injuries in a heavily smoking population.

Pre-weaning fluoxetine exposure caused anti-depressant like behavior at adulthood via perturbing tryptophan metabolism in rats.

The perinatal depression exposes the child to antidepressants during vulnerable window of development, which can chronically impact the mental wellbeing of new born. Active pharmaceuticals are not tested for this long term neurobehavioral aspect of toxicity during drug development process. Keeping this in view, the current study was designed to study the effect of pre-weaning fluoxetine exposure on depression-like behavior of the offspring upon attaining adulthood using FST (Forced swim test). Additionally, the brain tryptophan, 5-HT (5-hydroxytryptamine) and its metabolite 5-HIAA (5-hydroxyindoleacetic acid) levels were quantified using Enzyme linked Immunosorbent Assay (ELISA), while expression of SERT (serotonin receptor), 5-HT1A receptor, TPH (tryptophan hydroxylase) genes were monitored using qPCR. Our data showed that pre-weaning fluoxetine (10, 50 or 100 mg/kg) exposure decreased depression-like behavior. The 5-HT and 5-HIAA levels showed declining trend. However, the 5-HT synthetic precursor i.e. tryptophan levels were found to be significantly elevated in both brain and plasma as compared to control rats. The gene expression study did not reveal any significant alterations as compared to control. In conclusion, the present study demonstrate that pre-weaning fluoxetine exposure decreased depression-like behavior upon adulthood via perturbing tryptophan metabolism.

Synthesis and investigation of anti-COVID19 ability of ferrocene Schiff base derivatives by quantum chemical and molecular docking.

The recent outbreak of coronavirus disease (COVID-19) has rampaged the world with more than 236 million confirmed cases and over 4.8 million deaths across the world reported by the world health organization (WHO) till Oct 5, 2021. Due to the advent of different variants of coronavirus, there is an urgent need to identify effective drugs and vaccines to combat rapidly spreading virus varieties across the globe. Ferrocene derivatives have attained immense interest as anticancer, antifungal, antibacterial, and antiparasitic drug candidates. However, the ability of ferrocene as anti-COVID-19 is not yet explored. Therefore, in the present work, we have synthesized four new ferrocene Schiff bases (L1-L4) to understand the active sites and biological activity of ferrocene derivatives by employing various molecular descriptors, frontier molecular orbitals (FMO), electron affinity, ionization potential, and molecular electrostatic potential (MEP). A theoretical insight on synthesized ferrocene Schiff bases was accomplished by molecular docking, frontier molecular orbitals energies, active sites, and molecular descriptors which were further compared with drugs being currently used against COVID-19, i.e., dexamethasone, hydroxychloroquine, favipiravir (FPV), and remdesivir (RDV). Moreover, through the molecular docking approach, we recorded the inhibitions of ferrocene derivatives on core protease (6LU7) protein of SARS-CoV-2 and the effect of substituents on the anti-COVID activity of these synthesized compounds. The computational outcome indicated that L1 has a powerful 6LU7 inhibition of SARS-CoV-2 compared to the currently used drugs. These results could be helpful to design new ferrocene compounds and explore their potential application in the prevention and treatment of SARS-CoV-2.

Cooperative Power-Domain NOMA Systems: An Overview.

Interference has been a key roadblock against the effectively deployment of applications for end-users in wireless networks including fifth-generation (5G) and beyond fifth-generation (B5G) networks. Protocols and standards for various communication types have been established and utilised by the community in the last few years. However, interference remains a key challenge, preventing end-users from receiving the quality of service (QoS) expected for many 5G applications. The increased need for better data rates and more exposure to multimedia information lead to a non-orthogonal multiple access (NOMA) scheme that aims to enhance spectral efficiency and link additional applications employing successive interference cancellation and superposition coding mechanisms. Recent work suggests that the NOMA scheme performs better when combined with suitable wireless technologies specifically by incorporating antenna diversity including massive multiple-input multiple-output architecture, data rate fairness, energy efficiency, cooperative relaying, beamforming and equalization, network coding, and space-time coding. In this paper, we discuss several cooperative NOMA systems operating under the decode-and-forward and amplify-and-forward protocols. The paper provides an overview of power-domain NOMA-based cooperative communication, and also provides an outlook of future research directions of this area.

Optimal Path Routing Protocol for Warning Messages Dissemination for Highway VANET.

In vehicular ad hoc networks (VANETs), helpful information dissemination establishes the foundation of communication. One of the significant difficulties in developing a successful dissemination system for VANETs is avoiding traffic fatalities. Another essential success metric is the transfer of reliable and secure warning messages through the shortest path, particularly on highways with high mobility. Clustering vehicles is a general solution to these challenges, as it allows warning alerts to be re-broadcast to nearby clusters by fewer vehicles. Hence, trustworthy cluster head (CH) selections are critical to decreasing the number of retransmissions. In this context, we suggest a clustering technique called Optimal Path Routing Protocol for Warning Messages (OPRP) for dissemination in highway VANETs. OPRP relies on mobility measured to reinforce cluster creation, evade transmission overhead, and sustain message authenticity in a high mobility environment. Moreover, we consider communication between the cluster heads to reduce the number of transmissions. Furthermore, the cluster head is chosen using the median technique based on an odd or even number of vehicles for a stable and lengthy cluster life. By altering traffic densities and speeds, OPRP is compared with prominent schemes. Simulation results revealed that OPRP offers enhanced throughput, end-to-end delay, maximizing packet delivery ratio, and message validity.

Fabrication of moxifloxacin HCl-loaded biodegradable chitosan nanoparticles for potential antibacterial and accelerated cutaneous wound healing efficacy.

AIM: This work aims to formulate topical hybrid gel containing chitosan-coated moxifloxacin (MXF) HCl nanoparticles (NPs) with enhanced antibacterial and healing activity. METHODS: MXF HCl NPs prepared by the ionic gelation method were loaded onto a hybrid chitosan carbomer gel. Size analysis of the prepared NPs was performed using SEM and Zeta-sizer. Further characterisation was done using Fourier transforms infra-red spectroscopy (FTIR), X-ray diffraction (XRD), and Thermogravimetric analysis (TGA). Prepared gel was evaluated for its in vitro drug release, biocompatibility, antibacterial activity, and stability studies under storage conditions. In-vivo wound healing was measured by observing percentage reduction in wound. RESULTS: NPs have 359 ± 79 nm mean particle size, 31.01 mV zeta potential with 0.008 polydispersity index (PD1), 63.5% drug entrapment and 83 ± 3.5% drug release at pH 5.5. Hybrid chitosan carbomer gel showed good biocompatibility, antibacterial, in-vivo wound healing properties and stable properties. CONCLUSIONS: NP-loaded hybrid gel can be an effective treatment for acute and challenged topical wounds.

In Vitro and In Vivo Anti-Arthritic Potential of Caralluma tuberculata N. E. Brown. and Its Chemical Characterization.

Present research was planned to assess the in vitro and in vivo anti-arthritic potential of Caralluma tuberculata N. E. Brown. methanolic (CTME) and aqueous (CTAQ) extracts. Chemical characterization was done by high-performance liquid chromatography and gas chromatography−mass spectrometry analysis. The Complete Freund's Adjuvant (CFA) was injected in left hind paw of rat at day 1 and dosing at 150, 300 and 600 mg/kg was started on the 8th day via oral gavage in all groups except normal and disease control rats (which were given distilled water), whereas methotrexate (intraperitoneal; 1 mg/kg/mL) was administered to standard control. The CTME and CTAQ exerted significant (p < 0.01−0.0001) in vitro anti-arthritic action. Both extracts notably reduced paw edema, and restored weight loss, immune organs weight, arthritic score, RBCs, ESR, platelet count, rheumatoid factor (RF), C-reactive protein, and WBCs in treated rats. The plant extracts showed significant (p < 0.05−0.0001) downregulation of tumor necrosis factor-α, Interleukin-6, -1ß, NF-κB, and cyclooxygenase-2, while notably upregulated IL-4, IL-10, I-κBα in contrast to disease control rats. The plant extracts noticeably (p < 0.001−0.0001) restored the superoxide dismutase and catalase activities and MDA levels in treated rats. Both extracts exhibited significant anti-arthritic potential. The promising potential was exhibited by both extracts probably due to phenolic, and flavonoids compounds.