Significance of dietary quinoa husk (Chenopodium quinoa) in gene regulation for stress mitigation in fish.

The persistent challenges posed by pollution and climate change are significant factors disrupting ecosystems, particularly aquatic environments. Numerous contaminants found in aquatic systems, such as ammonia and metal toxicity, play a crucial role in adversely affecting aquaculture production. Against this backdrop, fish feed was developed using quinoa husk (the byproduct of quinoa) as a substitute for fish meal. Six isonitrogenous diets (30%) and isocaloric diets were formulated by replacing fish meal with quinoa husk at varying percentages: 0% quinoa (control), 15, 20, 25, 30 and 35%. An experiment was conducted to explore the potential of quinoa husk in replacing fish meal and assess its ability to mitigate ammonia and arsenic toxicity as well as high-temperature stress in Pangasianodon hypophthalmus. The formulated feed was also examined for gene regulation related to antioxidative status, immunity, stress proteins, growth regulation, and stress markers. The gene regulation of sod, cat, and gpx in the liver was notably upregulated under concurrent exposure to ammonia, arsenic, and high-temperature (NH3 + As + T) stress. However, quinoa husk at 25% downregulated sod, cat, and gpx expression compared to the control group. Furthermore, genes associated with stress proteins HSP70 and DNA damage-inducible protein (DDIP) were significantly upregulated in response to stressors (NH3 + As + T), but quinoa husk at 25% considerably downregulated HSP70 and DDIP to mitigate the impact of stressors. Growth-responsive genes such as myostatin (MYST) and somatostatin (SMT) were remarkably downregulated, whereas growth hormone receptor (GHR1 and GHRß), insulin-like growth factors (IGF1X, IGF2X), and growth hormone gene were significantly upregulated with quinoa husk at 25%. The gene expression of apoptosis (Caspase 3a and Caspase 3b) and nitric oxide synthase (iNOS) were also noticeably downregulated with quinoa husk (25%) reared under stressful conditions. Immune-related gene expression, including immunoglobulin (Ig), toll-like receptor (TLR), tumor necrosis factor (TNFα), and interleukin (IL), strengthened fish immunity with quinoa husk feed. The results revealed that replacing 25% of fish meal with quinoa husk could improve the gene regulation of P. hypophthalmus involved in mitigating ammonia, arsenic, and high-temperature stress in fish.

Native Mass Spectrometry Dissects the Structural Dynamics of an Allosteric Heterodimer of SARS-CoV-2 Nonstructural Proteins.

Structure-based drug design, which relies on precise understanding of the target protein and its interaction with the drug candidate, is dramatically expedited by advances in computational methods for candidate prediction. Yet, the accuracy needs to be improved with more structural data from high throughput experiments, which are challenging to generate, especially for dynamic and weak associations. Herein, we applied native mass spectrometry (native MS) to rapidly characterize ligand binding of an allosteric heterodimeric complex of SARS-CoV-2 nonstructural proteins (nsp) nsp10 and nsp16 (nsp10/16), a complex essential for virus survival in the host and thus a desirable drug target. Native MS showed that the dimer is in equilibrium with monomeric states in solution. Consistent with the literature, well characterized small cosubstrate, RNA substrate, and product bind with high specificity and affinity to the dimer but not the free monomers. Unsuccessfully designed ligands bind indiscriminately to all forms. Using neutral gas collision, the nsp16 monomer with bound cosubstrate can be released from the holo dimer complex, confirming the binding to nsp16 as revealed by the crystal structure. However, we observed an unusual migration of the endogenous zinc ions bound to nsp10 to nsp16 after collisional dissociation. The metal migration can be suppressed by using surface collision with reduced precursor charge states, which presumably resulted in minimal gas-phase structural rearrangement and highlighted the importance of complementary techniques. With minimal sample input (∼µg), native MS can rapidly detect ligand binding affinities and locations in dynamic multisubunit protein complexes, demonstrating the potential of an "all-in-one" native MS assay for rapid structural profiling of protein-to-AI-based compound systems to expedite drug discovery.

Optimization, In Vitro and Ex Vivo Assessment of Nanotransferosome Gels Infused with a Methanolic Extract of Solanum xanthocarpum for the Topical Treatment of Psoriasis.

The goal of this investigation is to improve the topical delivery of medicine by preparing and maximizing the potential of a nanotransferosome gel infused with Solanum xanthocarpum methanolic extract (SXE) to provide localized and regulated distribution. Thin-film hydration was used to create SXE-infused nanotransferosomes (SXE-NTFs), and a Box-Behnken design was used to improve them. Phospholipon 90G (X1), cholesterol (X2) and sodium cholate (X3) were chosen as the independent variables, and their effects on vesicle size (Y1), polydispersity index (PDI) (Y2) and the percentage of entrapment efficiency (EE) (Y3) were observed both individually and in combination. For the SXE-NTFs, the vesicle size was 146.3 nm, the PDI was 0.2594, the EE was 82.24 ± 2.64%, the drug-loading capacity was 8.367 ± 0.07% and the drug release rate was 78.86 ± 5.24%. Comparing the antioxidant activity to conventional ascorbic acid, it was determined to be 83.51 ± 3.27%. Ex vivo permeation tests revealed that the SXE-NTF gel (82.86 ± 2.38%) considerably outperformed the SXE gel (35.28 ± 1.62%) in terms of permeation. In addition, it seemed from the confocal laser scanning microscopy (CLSM) picture of the Wistar rat's skin that the rhodamine-B-loaded SXE-NTF gel had a higher penetration capability than the control. Dermatokinetic studies showed that the SXE-NTF gel had a better retention capability than the SXE gel. According to the experimental results, the SXE-NTF gel is a promising and successful topical delivery formulation.

Multifunctional role of dietary copper to regulate stress-responsive gene for mitigation of multiple stresses in Pangasianodon hypophthalmus.

It is an urgent needs to address climate change and pollution in aquatic systems using suitable mitigation measures to avoid the aquatic animals' extinction. The vulnerability and extinction of the aquatic animals in the current scenario must be addressed to enhance safe fish food production. Taking into consideration of such issues in fisheries and aquaculture, an experiment was designed to mitigate high temperature (T) and low pH stress, as well as arsenic (As) pollution in fish using copper (Cu) containing diets. In the present investigation, the Cu-containing diets graded with 0, 4, 8, and 12 mg kg-1 were prepared and fed to Pangasianodon hypophthalmus reared under As, low pH, and high-temperature stress. The gene expression was highly affected in terms of the primary, secondary, and tertiary stress response, whereas supplementation of Cu-containing diet mitigates the stress response. Oxidative stress genes such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were significantly upregulated by stressors (As, As + T, and As + pH + T). Whereas, heat shock protein (HSP 70), inducible nitric oxide synthase (iNOS), metallothionine (MT), caspase 3a (Cas 3a), and cytochrome P450 (CYP 450) were highly upregulated by stressors, while dietary Cu at 8 mg kg-1 diet significantly downregulated these gene expressions. Indeed, the immunity-related genes viz. TNFα, Ig, TLR, and immune-related attributes viz. albumin, globulin, total protein, A:G ratio, blood glucose, NBT, and myeloperoxidase (MPO) were also improved with Cu-containing diets. Cu containing diets substantially improved neurotransmitter enzyme (AChE) and vitamin C (Vit C). DNA damage was also reduced with supplementation of Cu at 8 mg kg-1 diet. The growth index viz. final body weight gain (%), specific growth rate, protein efficiency ratio, food conversion ratio, relative feed intake, and daily growth index were noticeably enhanced by Cu diets (4 and 8 mg kg-1 diet). The growth-related genes expressions viz. growth hormone (GH), growth hormone regulator 1 (Ghr1), growth hormone regulator ß (Ghrß,) myostatin (MYST), and somatostatin (SMT) supported the growth enhancement with Cu at 8 mg kg-1 diet. The bioaccumulation of As was reduced with Cu-containing diets. The fish were infected with Aeromonas hydrophila at the end of the 105 days experimental trial. Cu at 8 mg kg-1 diet improved immunity, reduced the cumulative mortality, and enhanced the relative percentage survival of the fish. The results revealed that the innovative Cu diets could reduce the extinction of the fish against climate change and pollution era and produce the safest production that is safe to humans for consumption.

Protective role of selenium and selenium-nanoparticles against multiple stresses in Pangasianodon hypophthalmus.

Pollution and climate change pose significant threats to aquatic ecosystems, with adverse impacts on aquatic animals, including fish. Climate change increases the toxicity of metal in aquatic ecosystems. To understand the severity of metal pollution and climate change, an experiment was conducted to delineate the mitigation potential of selenium (Se) and selenium nanoparticles (Se-NPs) against lead (Pb) and high temperature stress in Pangasianodon hypophthalmus. For the experiment, five isonitrogenous and isocaloric diets were prepared, varying in selenium supplementation as Se at 0, 1, and 2 mg kg-1 diet, and Se-NPs at 1 and 2 mg kg-1 diet. The fish in stressor groups were exposed to Pb (1/20th of LC50 concentration, 4 ppm) and high temperature (34 °C) throughout the experiment. The results demonstrated that dietary supplementation of Se at 1 and 2 mg kg-1 diet, as well as Se-NPs at 1 mg kg-1 diet, significantly reduced (p < 0.01) the levels of lactate dehydrogenase and malate dehydrogenase in both liver and muscle tissues. Additionally, the levels of alanine aminotransferase and aspartate aminotransferase in both gill and liver tissues were significantly decreased (p < 0.01) with the inclusion of Se and Se-NPs in the diets. Furthermore, the enzymes glucose-6-phosphate dehydrogenase in gill and liver tissues, fructose 1,6-bisphosphatase in liver and muscle tissues, and acid phosphatase in liver tissue were remarkably reduced (p < 0.01) due to the supplementation of Se and Se-NPs. Moreover, dietary supplementation of Se and Se-NPs significantly enhanced (p < 0.01) the activity of pyruvate kinase, glucokinase, hexokinase, alkaline phosphatase, ATPase, protease, amylase, lipase, and RNA/DNA ratio in the fish. Histopathological examination of gill and liver tissues also indicated that Se and Se-NPs protected against structural damage caused by lead and high-temperature stress. Moreover, the study examined the bioaccumulation of selenium and lead in muscle, water, and diets. The aim of the study revealed that Se and Se-NPs effectively protected the fish from lead toxicity and high-temperature stress, while also improving the function of cellular metabolic enzymes in P. hypophthalmus.

Dietary manganese nano-particles improves gene regulation and biochemical attributes for mitigation of lead and ammonia toxicity in fish.

In the present study, we explored the capability of manganese nanoparticles (Mn-NPs) to alleviate the toxicity induced by lead (Pb) and ammonia (NH3) toxicity in Oreochromis niloticus (GIFT strain). The experiment followed a completely randomized design, including a control group (Mn-NPs-0 mg kg-1 diet) and groups exposed to Pb and NH3 alongwith Mn-NPs at 2 and 3 mg kg-1. Cortisol levels were significantly elevated in Pb + NH3 group whereas reduced by Mn-NPs diets. Gene expressions of HSP 70, iNOS, CYP 450, and Cas 3a were notably upregulated by Pb + NH3 group and downregulated by Mn-NPs diets. The cellular metabolic enzymes were affected by Pb + NH3 exposure and mitigated by Mn-NPs diets. The liver and kidney exhibited reduced activities of catalase, superoxide dismutase, and glutathione-s-transferase with Mn-NPs diets. Concurrently, immune-related genes such as total immunoglobulin (Ig) and tumor necrosis factor (TNFα) were upregulated in the Mn-NPs-fed groups. Growth performance indicators, including weight gain %, feed conversion ratio, specific growth rate, protein efficiency ratio, and relative feed intake were adversely affected by Pb + NH3 stress but improvement with Mn-NPs diets. Genes associated with growth performance, such as growth hormone (GH), growth hormone regulatory (GHR1), and myostatin, exhibited enhancements in response to Mn-NPs diets. Digestive enzymes, including protease and amylase were also enhanced by Mn-NPs diets. Additionally, Mn-NPs diets led to a reduction in the bioaccumulation of lead. This study aims to investigate the role of Mn-NPs in mitigating the effects of lead and ammonia toxicity on fish by examining various biochemical and gene regulatory factors to enhance fish wellbeing.

Tumor size dependent MNP dose evaluation in realistic breast tumor models for effective magnetic hyperthermia.

The goal of the current investigation is to determine the breast tumor size-dependent MNP (Magnetic nano-particle) dose (mg/cm3) that can induce the required therapeutic effects during magnetic nanoparticle hyperthermia (MNH). The investigation is done through the MNH simulations on the tumor models generated from DCE_MRI DICOM images of breast cancer from TCIA ('The Cancer Imaging Archive'). Five tumor models are created from MRI data using 3D slicer software having size range of 3 cm3 to 15 cm3. The FEM-based solver (COMSOL multi-physics) is used to simulate bioheat transfer physics in all five extracted models. Single and multi-point injection strategies have been adopted to induce MNP in tumor tissues. The required MNP dose that may induce necessary therapeutic effects is evaluated by comparing the therapeutic effects produced by constant dose (CD) (5 mg/cm3) and variable reduced dose (RD) (5.5-2.8 mg/cm3) methodologies. Results show that for the requisite therapeutic effects, injected MNP doses (mg/cm3) should not remain constant as the size of the tumor increases. In fact, MNP dose  (mg/cm3) should be reduced as the size of the tumor increases. Results also show that RD works better with a multi-injection strategy than a single injection of MNP. It has been found that the effective MNP dose  (mg/cm3) is reduced by 50 % for the biggest tumor size (15 cm3) using multi-injection MNP delivery with respect to the smallest tumor (3 cm3) selected in this study.

Manganese nanoparticles control the gene regulations against multiple stresses in Pangasianodon hypophthalmus.

Ammonia and arsenic pollution, along with the impact of climate change, represent critical factors influencing both the quantity and quality of aquaculture production. Recent developments have underscored the significance of these issues, as they not only disrupt aquatic ecosystems but also have far reaching consequences for human health. To addressed above challenges, an experiment was conducted to delineate the potential of manganese nanoparticles (Mn-NPs) to mitigate arsenic and ammonia pollution as well as high temperature stress in Pangasianodon hypophthalmus. The fish were exposed to different combination of arsenic and ammonia pollution as well as high temperature stress, while simultaneously incorporating diets enriched with Mn-NPs. The inclusion of Mn-NPs at 3 mg kg-1 in the diet led to a noteworthy downregulation of cortisol and HSP 70 gene expression, indicating their potential in mitigating stress responses. Furthermore, immune related gene expressions were markedly altered in response to the stressors but demonstrated improvement with the Mn-NPs diet. Interestingly, the expression of inducible nitric oxide synthase (iNOS), caspase (CAS), metallothionine (MT) and cytochrome P450 (CYP450) genes expression were prominently upregulated, signifying a stress response. Whereas, Mn-NPs at 3 mg kg-1 diet was significantly downregulated theses gene expression and reduces the stress. In addition to stress-related genes, we evaluated the growth-related gene expressions such as growth hormone (GH), growth hormone regulator 1 (GHR1 and GHRß), Insulin like growth factor (IGF1 and IGF2) were significantly upregulated whereas, myostatin and somatostatin were downregulated upon the supplementation of dietary Mn-NPs with or without stressors in fish. The gene expression of DNA damage inducible protein and DNA damage in response to head DNA % and tail DNA % was protected by Mn-NPs diets. Furthermore, Mn-NPs demonstrated a capacity to enhance the detoxification of arsenic in different fish tissues, resulting in reduced bioaccumulation of arsenic in muscle and other tissues. This finding highlights Mn-NPs as a potential solution for addressing bioaccumulation associated risks. Our study aimed to comprehensively examined the role of dietary Mn-NPs in mitigating the multiple stressors using gene regulation mechanisms, with enhancing the productive performance of P. hypophthalmus.

Effective networks mediate right hemispheric dominance of human 40 Hz auditory steady-state response.

Auditory steady-state responses (ASSR) are induced from the brainstem to the neocortex when humans hear periodic amplitude-modulated tonal signals. ASSRs have been argued to be a key marker of auditory temporal processing and pathological reorganization of ASSR - a biomarker of neurodegenerative disorders. However, most of the earlier studies reporting the neural basis of ASSRs were focused on looking at individual brain regions. Here, we seek to characterize the large-scale directed information flow among cortical sources of ASSR entrained by 40 Hz external signals. Entrained brain rhythms with power peaking at 40 Hz were generated using both monaural and binaural tonal stimulation. First, we confirm the presence of ASSRs and their well-known right hemispheric dominance during binaural and both monaural conditions. Thereafter, reconstruction of source activity employing individual anatomy of the participant and subsequent network analysis revealed that while the sources are common among different stimulation conditions, differential levels of source activation and differential patterns of directed information flow among sources underlie processing of binaurally and monaurally presented tones. Particularly, we show bidirectional interactions involving the right superior temporal gyrus and inferior frontal gyrus underlie right hemispheric dominance of 40 Hz ASSR during both monaural and binaural conditions. On the other hand, for monaural conditions, the strength of inter-hemispheric flow from left primary auditory areas to right superior temporal areas followed a pattern that comply with the generally observed contralateral dominance of sensory signal processing.

Abiotic and biotic stress alleviating effects of the medicinal and aromatic plant-derived product on striped catfish Pangasianodonhypophthalmus.

Intensification of aquaculture production leads to abiotic and biotic stresses, which are further induced by the impact of climate change. Thus, it is important to explore a combined strategy to alleviate multiple stresses in fish. In the present investigation, the removal of nitrogenous metabolites from aquaponics water was studied using products derived from five different locally available medicinal and aromatic plants (MAPs) namely banana stem (Musa Accuminata), Aloe vera, Mint (Minata sepicata), Indian beech/Pongameoil-tree/Karanj (Pongamia pinnatum), and Coat Button/Mexican daisy/Dagadipala (Tridax procrumbens) in the batch experiment for 24 h. A reduction of 91-94% in the ammonia level and 75-80% removal of nitrite-N in the treatments with products derived from mint, banana stem, and aloe vera has been observed. Mint product was also found to be bactericidal against fish pathogenic bacteria. Based on this dual function of mint, further study was conducted under wet-lab conditions to evaluate the possible protective role of the mint-based product in dry powder form against abiotic stresses caused by nitrogenous toxicants for 24 h and 45 days multiple stresses caused by nitrogenous toxicants in freshwater stocked with eight fingerlings of Pangasianodon hypophthalmus of the initial weight of 8 ± 0.5g for 24 h and 8.82 ± 0.75g for 45 days. The results revealed that mint-derived plant product has better anti-stress properties in terms of their bioremediation effectiveness in lowering ammonia and nitrite. Mint also improved the fish growth performance with better physiological responses and anti-oxidative status and reduced the cellular metabolic stress in fish reared under ammonia, as further indicated by reduced oxidative stress parameters, and tissue biochemical indices. Overall, mint showed its main properties as a growth promoter, and immune enhancer, where this medicinal plant product acts as a bioremediation and antibacterial agent to the host immune system. This has potential applications in the environmental and health management of aquaculture.

Nano­zinc enhances gene regulation of non­specific immunity and antioxidative status to mitigate multiple stresses in fish.

The toxicity of ammonia surged with arsenic pollution and high temperature (34 °C). As climate change enhances the pollution in water bodies, however, the aquatic animals are drastically affected and extinct from nature. The present investigation aims to mitigate arsenic and ammonia toxicity and high-temperature stress (As + NH3 + T) using zinc nanoparticles (Zn-NPs) in Pangasianodon hypophthalmus. Zn-NPs were synthesized using fisheries waste to developing Zn-NPs diets. The four isonitrogenous and isocaloric diets were formulated and prepared. The diets containing Zn-NPs at 0 (control), 2, 4 and 6 mg kg-1 diets were included. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-s-transferase (GST) were noticeably improved using Zn-NPs diets in fish reared under with or without stressors. Interestingly, lipid peroxidation was significantly reduced, whereas vitamin C and acetylcholine esterase were enhanced with supplementation of Zn-NPs diets. Immune-related attributes such as total protein, globulin, albumin, myeloperoxidase (MPO), A:G ratio, and NBT were also improved with Zn-NPs at 4 mg kg-1 diet. The immune-related genes such as immunoglobulin (Ig), tumor necrosis factor (TNFα), and interleukin (IL1b) were strengthening in the fish using Zn-NPs diets. Indeed, the gene regulations of growth hormone (GH), growth hormone regulator (GHR1), myostatin (MYST) and somatostatin (SMT) were significantly improved with Zn-NPs diets. Blood glucose, cortisol and HSP 70 gene expressions were significantly upregulated by stressors, whereas the dietary Zn-NPs downregulated the gene expression. Blood profiling (RBC, WBC and Hb) was reduced considerably with stressors (As + NH3 + T), whereas Zn-NPs enhanced the RBC, WBC, and Hb count in fish reread in control or stress conditions. DNA damage-inducible protein gene and DNA damage were significantly reduced using Zn-NPs at 4 mg kg-1 diet. Moreover, the Zn-NPs also enhanced the arsenic detoxification in different fish tissues. The present investigation revealed that Zn-NPs diets mitigate ammonia and arsenic toxicity, and high-temperature stress in P. hypophthalmus.

Effects of injection rates and tissue diffusivity in magnetic nano-particle hyperthermia.

Effects of injection rate and tumor physiology on the diffusion of magnetic nano-particles (MNPs) and temperature profile during magnetic hyperthermia are investigated in this work. The study considers three injection rates (2.5 µL/min, 10 µL/min, and 40 µL/min), and two MNP diffusion coefficients (10-9 m2/s and 10-11 m2/s). The simulation of this physics has been done on 3D tumor surrounded by healthy tissue. Transient MNP distribution in tissue is evaluated using Darcy's flow model and the MNP transport (convection-diffusion) equation. The temperature profile in the tumor model is computed by solving Penne's bioheat transfer equation (PBHTE). Results show tumors with high collagen content (with low MNP diffusivity) are more restrictive towards MNP transport than tumors having low collagen content. Thus, tumors with low MNP diffusivity need a higher injection rate to increase the homogeneity of MNP concentration as well as temperature profile during thermo-therapy. Results also show that, MNP fluid injected with a higher injection rate produces a more uniform MNP concentration up to greater depth than the lower injection rate.

Machine intelligence-guided selection of optimized inhibitor for human immunodeficiency virus (HIV) from natural products.

The human immunodeficiency virus (HIV) connects to the cluster of differentiation (CD4) and any of the entry co-receptors (CCR5 and CXCR4); followed by unloading the viral genome, reverse transcriptase, and integrase enzymes within the host cell. The co-receptors facilitate the entry of virus and vital enzymes, leading to replication and pre-maturation of viral particles within the host. The protease enzyme transforms the immature viral vesicles into the mature virion. The pivotal role of co-receptors and enzymes in homeostasis and growth makes the crucial target for anti-HIV drug discovery, and the availability of X-ray crystal structures is an asset. Here, we used the machine intelligence-driven framework (A-HIOT) to identify and optimize target-based potential hit molecules for five significant protein targets from the ZINC15 database (natural products dataset). Following validation with dynamic motion behavior analysis and molecular dynamics simulation, the optimized hits were evaluated using in silico ADMET filtration. Furthermore, three molecules were screened, optimized, and validated: ZINC00005328058 for CCR5 and protease, ZINC000254014855 for CXCR4 and integrase, and ZINC000000538471 for reverse transcriptase. In clinical trials, the ZINC000254014855 and ZINC000254014855 were passed in primary screens for vif-HIV-1, and we reported the specific receptor as well as interactions. As a result, the validated molecules may be investigated further in experimental studies targeting specific receptors in order to design and synergize an anti-HIV regimen.

Health risk assessment and metal contamination in fish, water and soil sediments in the East Kolkata Wetlands, India, Ramsar site.

East Kolkata Wetlands (EKW) is an important site for fish culture in sewage-fed areas, which are major receivers of pollutants and wastages from Kolkata. EKW is internationally important as the Ramsar site was declared on Aug 2002 with an area of 125 km2. EKW is a natural water body where wastewater-fed natural aquaculture has been practiced for more than 70 years. It is ecologically vulnerable due to the discharge of toxic waste through sewage canals from cities. Assessing the EKW to understand the inflow and load of the toxic metal (s) in fish, water, and sediments samples is essential. The field (samples collection from 13 sites) and lab (determination of toxic level of metals) based research were carried out to assess metal toxicity and health risk assessment in EKW. The levels of eighteen metals (18), namely Chromium, Vanadium, Cobalt, Manganese, Copper, Nickel, Zinc, Silver, Molybdenum, Arsenic, Selenium, Tin, Gallium, Germanium, Strontium, Cadmium, Mercury, and Lead, were determined using Inductively coupled plasma mass spectrometry (ICP-MS) in five fish tissues viz. muscle, liver, kidney, gill and brain, along with the water samples and soil sediments in 13 sampling sites. The bioaccumulation and concentration of metals in fish tissues, soil sediments, and water samples were well within the safe level concerning the recommendation of different national and international agencies except for a few metals in a few sampling sites like Cd, As, and Pb. The geoaccumulation index (Igeo) was also determined in the soil sediments, indicating moderate arsenic, selenium, and mercury contamination in a few sites. The contamination index in water was also determined in 13 sampling sites. The estimated daily intake (EDI), reference dose (RfD), target hazard quotient (THQ), slope factor and cancer risk of Cr, Mn, Co, Ni, Cu, Zn, As, Se, Cd, Pb and Hg from fish muscle were determined. Based on the results of the present investigation, it is concluded that fish consumption in the East Kolkata Wetland (EKW) is safe. The effects of bioaccumulation of metals in muscle tissue were well within the safe level for consumption as recommended by WHO/FAO.

Nano-copper Enhances Gene Regulation of Non-specific Immunity and Antioxidative Status of Fish Reared Under Multiple Stresses.

Arsenic pollution, water temperature, and pH are the major concern for aquaculture. Moreover, the aim of the present investigation was to delineate the role of nano-copper (Cu-NPs) in the mitigation of arsenic toxicity, high temperature (34 °C) and low pH (6.5) stress on Pangasianodon hypophthalmus. Four isonitrogenous and isocaloric experimental diets of Cu-NPs at 0, 1.0, 1.5 and 2.0 mg kg-1 were formulated and prepared. Arsenic pollution, low pH and high temperature stress significantly reduced the anti-oxidative status (super oxide dismutase, catalase, glutathione peroxidase and glutathione-s-transferase), lipid peroxidation, total anti-oxidative capacity and lipid profiling (cholesterol, total lipid, phospholipid, very low-density lipoprotein and triglyceride). Further, the supplementation of Cu-NPs at 1.5 and 1.0 mg kg-1 diets noticeably improve the anti-oxidant status and capacity. The stressors groups (As + pH + T, As + T and As) significantly reduced fish immunity viz. albumin, globulin, total protein, albumin globulin ratio (A:G ratio), myeloperoxidase, respiratory burst activities, tumor necrosis factor, total immunoglobulin, and interleukin. Whereas supplementation of Cu-NPs at 1.5 and 1.0 mg kg-1 diets improved the immunity of the fish reared under multiple stresses (As + pH + T). Tail DNA %, DNA damage-inducible protein (DDIP) and inducible nitric oxide (iNOS) synthase gene expression were significantly enhanced with exposure to arsenic, low pH and high temperature but supplementation of Cu-NPs protects the tissues against DNA damage and improved the gene expression of iNOS and DDIP. Cu-NPs at 1.5 and 1.0 mg kg-1 diets significantly enhanced the body weight gain %, protein efficiency ratio, specific growth rate, daily growth index, relative feed intake and reduced the feed conversion ratio. Whereas, the growth-related gene expression such as myostatin (MYST), somatostatin (SMT) was downregulated by Cu supplementation and upregulated the gene expression of growth hormone regulator 1 and ß (GHR1 and GHR ß) and growth hormone (GH) gene in fish. Dietary Cu-NPs supplementation protects the fish against bacterial infection and enhances arsenic detoxification in different tissues. The present investigation revealed that supplementation of Cu-NPs at 1.5 and 1.0 mg kg-1 diet has the potential to mitigate multiple stress (As + pH + T) in fish.

A comprehensive review on variants of SARS-CoVs-2: Challenges, solutions and open issues.

SARS-CoV-2 is an infected disease caused by one of the variants of Coronavirus which emerged in December 2019. It is declared a pandemic by WHO in March 2020. COVID-19 outbreak has put the world on a halt and is a major threat to the public health system. It has shattered the world with its effects on different areas as the pandemic hit the world in a number of waves with different variants and mutations. Each variant and mutation have different transmission and infection rates in the human population. More than 609 million people have tested positive and more than 6.5 million people have died due to this disease as per 14th September 2022. Despite of numerous efforts, precautions and vaccination the infection has grown rapidly in the world. In this paper, we aim to give a holistic overview of COVID-19 its variants, game theory perspective, effects on the different social and economic areas, diagnostic advancements, treatment methods. A taxonomy is made for the proper insight of the work demonstrated in the paper. Finally, we discuss the open issues associated with COVID-19 in different fields and futuristic research trends in the area. The main aim of the paper is to provide comprehensive literature that covers all the areas and provide an expert understanding of the COVID-19 techniques and potentially be further utilized to combat the outbreak of COVID-19.

Exploring mitigating role of zinc nanoparticles on arsenic, ammonia and temperature stress using molecular signature in fish.

BACKGROUND: The pollution and climate change in aquatic ecosystems are major problems threatening the aquatic organisms for existence in the recent timeline, which promotes the extinction of the fish species. However, the present study dealt with zinc nanoparticles (Zn-NPs) in mitigating arsenic, ammonia and high temperature stresses in Pangasianodon hypophthalmus. MATERIALS AND METHODS: To studying different gene expressions, an experiment was conducted to mitigate the multiple stressors using dietary Zn-NPs at 0, 2, 4, and 6 mg kg-1 diets. In the present investigation, the gene expressions studies were performed for growth hormone regulator 1 (GHR1), growth hormone regulator ß (GHRß), growth hormone (GR) in liver and gill tissue as well as myostatin (MYST) and somatostatin (SMT) in the muscle tissue. The anti-oxidative genes CAT, SOD and GPx in liver and gill tissues were also analysed. Expression studies for stress responsive heat shock protein gene (HSP70), DNA damage inducible protein, inducible nitric oxide synthase (iNOS), immune related genes such as interleukin (IL), tumour necrosis factor (TNFα), toll like receptor (TLR) and immunoglobulin were performed. At the end of the experiment the fish were infected with Aeromonas hydrophila to evaluate the immunomodulatory role of Zn-NPs. RESULTS: In the present investigation, the growth hormone regulator 1 (GHR1), growth hormone regulator ß (GHRß), growth hormone (GR) in liver and gill as well as myostatin (MYST) and somatostatin (SMT) in muscle were noticeably altered, whereas, Zn-NPs at 4 mg kg-1 diet improved gene expressions. The anti-oxidant gene viz. CAT, SOD and GPx in liver and gill tissues were upregulated by stressors such as As, NH3, NH3+T. As+T and As+NH3+T. Therefore, anti-oxidant genes were noticeably improved with dietary Zn-NPs diet. The stress protein gene (HSP70), DNA damage inducible protein, inducible nitric oxide synthase (iNOS) was significantly upregulated, whereas, Zn-NPs diet was applied to the corrected gene regulation. Similarly, immune related genes such as interleukin (IL), tumour necrosis factor (TNFα), toll like receptor (TLR) and immunoglobulin were highly affected by stressors. Dietary Zn-NPs at 4 mg kg-1 diet was improved all the immune related gene expression and mitigate arsenic, ammonia and high temperature stress in fish. CONCLUSION: The present investigation revealed that Zn-NPs at 4.0 mg kg-1 diet has enormous potential to modulates arsenic, ammonia and high temperature stress, and protect against pathogenic infections in fish.

Selenium nanoparticles and omega-3 fatty acid enhanced thermal tolerance in fish against arsenic and high temperature.

The aquatic ecosystem is prone to global climate change and pollution affecting aquatic animals, including fish. In light of the above, we experimented with delineate the role of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with selenium nanoparticles (Se-NPs) to enhance the thermal tolerance in Pangasianodon hypophthalmus reared under control or concurrent exposure to high temperature and arsenic (As + T) for 112 days. Se-NPs were synthesized using the green approach. Four experimental diets viz. EPA + DHA at 0.2, 0.4 and 0.6 % along with Se-NPs at 0.2 mg kg-1 diet were formulated and prepared. End of the experiment (112 days), the thermal tolerance viz. CTmin (critical thermal minima) CTmax (critical thermal maxima), LTmin (lethal thermal minima) and LTmax (lethal thermal maxima) were determined. Supplementation of EPA + DHA along with Se-NPs noticeably improved the thermal tolerance of the fish reared under stress (As + T) and control condition. Superoxide dismutase, glutathione-s-transferase, catalase, glutathione peroxides and LPO were enhanced by As + T, whereas EPA + DHA at 0.4 % and Se-NPs reduced the oxidative stress. Further, acetylcholine esterase was inhibited by arsenic alone and concurrent with temperature but dietary supplementation significantly enhanced the brain AChE activity. Exposure to arsenic and concurrent with a temperature significantly reduced the ATPase. Whereas supplementation of EPA + DHA at 0.4 % and Se-NPs enhanced the ATPase in liver and gill tissues. Arsenic bioaccumulation was also reduced with EPA + DHA at 0.4 % and Se-NPs. The present investigation concluded that EPA + DHA at 0.4 % and Se-NPs at 0.2 mg kg-1 diet protects the P. hypophthalmus against arsenic pollution and thermal stress.

Sustained drug delivery strategies for treatment of common substance use disorders: Promises and challenges.

Substance use disorders (SUDs) are a leading cause of death and other ill health effects in the United States and other countries in the world. Several approaches ranging from detoxification, behavioral therapy, and the use of antagonists or drugs with counter effects are currently being applied for its management. Amongst these, drug therapy is the mainstay for some drug abuse incidences, as is in place specifically for opioid abuse or alcohol dependence. The severity of the havocs observed with the SUDs has triggered constant interest in the discovery and development of novel medications as well as suitable or most appropriate methods for the delivery of these agents. The chronic need of such drugs in users warrants the need for their prolonged or sustained systemic availability. Further, the need to improve patient tolerance to medication, limit invasive drug use and overall treatment outcome are pertinent considerations for embracing sustained release designs for medications used in managing SUDs. This review aims to provide an overview on up-to-date advances made with regards to sustained delivery systems for the drugs for treatment of different types of SUDs such as opioid, alcohol, tobacco, cocaine, and cannabis use disorders. The clinical relevance, promises and the limitations of deployed sustained release approaches along with future opportunities are discussed.

Advanced metal and carbon nanostructures for medical, drug delivery and bio-imaging applications.

Nanoparticles (NPs) offer great promise for biomedical, environmental, and clinical applications due to their several unique properties as compared to their bulk counterparts. In this review article, we overview various types of metal NPs and magnetic nanoparticles (MNPs) in monolithic form as well as embedded into polymer matrices for specific drug delivery and bio-imaging fields. The second part of this review covers important carbon nanostructures that have gained tremendous attention recently in such medical applications due to their ease of fabrication, excellent biocompatibility, and biodegradability at both cellular and molecular levels for phototherapy, radio-therapeutics, gene-delivery, and biotherapeutics. Furthermore, various applications and challenges involved in the use of NPs as biomaterials are also discussed following the future perspectives of the use of NPs in biomedicine. This review aims to contribute to the applications of different NPs in medicine and healthcare that may open up new avenues to encourage wider research opportunities across various disciplines.