Investigating the potential of monocyclic B9N9 and C18 rings for the electrochemical sensing, and adsorption of carbazole-based anti-cancer drug derivatives: DFT-based first-principle study.

CONTEXT: For the first time, the use of monocyclic rings C18 and B9N9 as sensors for the sensing of carbazole-based anti-cancer drugs, such as tetrahydrocarbazole (THC), mukonal (MKN), murrayanine (MRY), and ellipticine (EPT), is described using DFT simulations and computational characterization. The geometries, electronic properties, stability studies, sensitivity, and adsorption capabilities of C18 and B9N9 counterparts towards the selected compounds confirm that the analytes interact through active cavities of the C18 and B9N9 rings of the complexes. METHODS: Based on the interaction energies, the sensitivity of surfaces towards EPT, MKN, MRY, and THC analytes is observed. The interaction energy of EPT@B9N9, MKN@B9N9, MRY@B9N9, and THC@B9N9 complexes are observed - 20.40, - 19.49, - 20.07, and - 18.27 kcal/mol respectively which is more exothermic than EPT@C18, MKN@C18, MRY@C18, and THC@C18 complexes are - 16.37, - 13.97, - 13.96, and - 11.39 kcal/mol respectively. According to findings from the quantum theory of atoms in molecules (QTAIM) and the reduced density gradient (RDG), dispersion forces play a significant role in maintaining the stability of these complexes. The electronic properties including FMOs, density of states (DOS), natural bond orbitals (NBO), charge transfer, and absorption studies are carried out. In comparison of B9N9 and C18, the analyte recovery time for C18 is much shorter (9.91 × 10-11 for THC@C18) than that for B9N9 shorter recovery time value of 3.75 × 10-9 for EPT@B9N9. These results suggest that our reported sensors B9N9 and C18 make it faster to detect adsorbed molecules at room temperature. The sensor response is more prominent in B9N9 due to its fine energy gap and high adsorption energy. Consequently, it is possible to think of these monocyclic systems as a potential material for sensor applications.

A decay-modeled compressed sensing reconstruction approach for non-Cartesian hyperpolarized 129Xe MRI.

PURPOSE: Hyperpolarized 129Xe MRI benefits from non-Cartesian acquisitions that sample k-space efficiently and rapidly. However, their reconstructions are complex and burdened by decay processes unique to hyperpolarized gas. Currently used gridded reconstructions are prone to artifacts caused by magnetization decay and are ill-suited for undersampling. We present a compressed sensing (CS) reconstruction approach that incorporates magnetization decay in the forward model, thereby producing images with increased sharpness and contrast, even in undersampled data. METHODS: Radio-frequency, T1, and T 2 * $$ {\mathrm{T}}_2^{\ast } $$ decay processes were incorporated into the forward model and solved using iterative methods including CS. The decay-modeled reconstruction was validated in simulations and then tested in 2D/3D-spiral ventilation and 3D-radial gas-exchange MRI. Quantitative metrics including apparent-SNR and sharpness were compared between gridded, CS, and twofold undersampled CS reconstructions. Observations were validated in gas-exchange data collected from 15 healthy and 25 post-hematopoietic-stem-cell-transplant participants. RESULTS: CS reconstructions in simulations yielded images with threefold increases in accuracy. CS increased sharpness and contrast for ventilation in vivo imaging and showed greater accuracy for undersampled acquisitions. CS improved gas-exchange imaging, particularly in the dissolved-phase where apparent-SNR improved, and structure was made discernable. Finally, CS showed repeatability in important global gas-exchange metrics including median dissolved-gas signal ratio and median angle between real/imaginary components. CONCLUSION: A non-Cartesian CS reconstruction approach that incorporates hyperpolarized 129Xe decay processes is presented. This approach enables improved image sharpness, contrast, and overall image quality in addition to up-to threefold undersampling. This contribution benefits all hyperpolarized gas MRI through improved accuracy and decreased scan durations.

Deciphering the electrochemical sensing capability of novel Ga12As12 nanocluster towards chemical warfare phosgene gas: insights from DFT.

The applications of 3D inorganic nanomaterials in environmental and agriculture monitoring have been exploited continuously; however, the utilization of semiconductor nanoclusters, especially for detecting warfare agents, has not been fully investigated yet. To fill this gap, the molecular modelling of novel inorganic semiconductor nanocluster Ga12As12 as a sensor for phosgene gas (highly toxic for living things and the environment) is accomplished employing benchmark DFT and TD-DFT investigations. Computational tools have been applied to explore different adsorption sites and the potential sensing capability of the Ga12As12 nanoclusters. The calculated adsorption energy (-21.34 ± 2.7 kcal mol-1) for ten selected complexes, namely, Pgn-Cl@4m-ring (MS1), Pgn-Cl@6m-ring (MS2), Pgn-Cl@XY66 (MS3), Pgn-O@4m-ring (MS4), Pgn-O@XY66 (MS5), Pgn-O@XY64 (MS6), Pgn-O@Y (MS7), Pgn-planar@Y (MS8), Pgn-planar@X (MS9), and Pgn-planar@4m-ring (MS10), manifest the remarkable and excessive adsorption response of the studied nanoclusters. The explored molecular electronic properties, such as interaction distance (3.05 ± 0.5 Å), energy gap (∼2.17 eV), softness (∼0.46 eV), hardness (1.10 ± 0.01 eV), electrophilicity index (10.27 ± 0.45 eV), electrical conductivity (∼1.98 × 109), and recovery time (∼3 × 10-12 s-1) values, ascertain the elevated reactivity and an imperishable sensitivity of the Ga12As12 nanocluster, particularly for its complex MS8. QTAIM analysis exhibits the presence of a strong electrostatic bond (positive ∇2ρ(r) values), electron delocalization (ELF < 0.5), and a strong chemical bond (because of high all-electron density values). In addition, NBO analysis explores the lone pair electron delocalization of phosgene to the nanocluster stabilized by intermolecular charge transfer (ICT) and different kinds of non-covalent interactions. Also, the green region existence expressed by NCI analysis (between the nanocluster and adsorbate) stipulate the energetic and dominant interactions. Furthermore, the UV-Vis, thermodynamic analysis, and density of state (DOS) demonstrate the maximum absorbance (562.11 nm) and least excitation energy (2.21 eV) by the complex MS8, the spontaneity of the interaction process, and the significant changes in HOMO and LUMO energies, respectively. Thus, the Ga12As12 nanocluster has proven to be a promising influential sensing material to monitor phosgene gas in the real world, and this study will emphasize the informative knowledge for experimental researchers to use Ga12As12 as a sensor for the warfare agent (phosgene).

Cobalt Iron Oxide (CoFe2O4) Nanoparticles Induced Toxicity in Rabbits.

The market for nanoparticles has grown significantly over the past few decades due to a number of unique qualities, including antibacterial capabilities. It is still unclear how nanoparticle toxicity works. In order to ascertain the toxicity of synthetic cobalt iron oxide (CoFe2O4) nanoparticles (CIONPs) in rabbits, this study was carried out. Sixteen rabbits in total were purchased from the neighborhood market and divided into two groups (A and B), each of which contained eight rabbits. The CIONPs were synthesized by the co-precipitation method. Crystallinity and phase identification were confirmed by X-ray diffraction (XRD). The average size of the nanoparticles (13.2 nm) was calculated by Scherrer formula (Dhkl = 0.9 λ/ß cos θ) and confirmed by TEM images. The saturation magnetization, 50.1 emug-1, was measured by vibrating sample magnetometer (VSM). CIONPs were investigated as contrast agents (CA) for magnetic resonance images (MRI). The relaxivity (r = 1/T) of the MRI was also investigated at a field strength of 0.35 T (Tesla), and the ratio r2/r1 for the CIONPs contrast agent was 6.63. The CIONPs were administrated intravenously into the rabbits through the ear vein. Blood was collected at days 5 and 10 post-exposure for hematological and serum biochemistry analyses. The intensities of the signal experienced by CA with CIONPs were 1427 for the liver and 1702 for the spleen. The treated group showed significantly lower hematological parameters, but significantly higher total white blood cell counts and neutrophils. The results of the serum biochemistry analyses showed significantly higher and lower quantities of different serum biochemical parameters in the treated rabbits at day 10 of the trial. At the microscopic level, different histological ailments were observed in the visceral organs of treated rabbits, including the liver, kidneys, spleen, heart, and brain. In conclusion, the results revealed that cobalt iron oxide (CoFe2O4) nanoparticles induced toxicity via alterations in multiple tissues of rabbits.

Elevated expression of immune and DNA repair genes in mated queens and kings of the Reticulitermes chinensis termites.

Studies have identified that mating induces a series of physiological changes in animals. In this period, males tending to invest more energy, immune peptides, and other substances to reduce the cost of living for females. This results in lower survival rates in later life than females. Meanwhile, both males and females shorten lifespans due to reproduction. However, the reasons why termites' queens and kings are both extremely long-lived and highly fecund are unclear. Therefore, this study aimed to examine the effects of mating on the expression of immune and DNA repair genes for lifespan extension in termite queens and kings. Here, we reported that mated queens show relatively higher expression of immune genes (phenoloxidase, denfensin, termicin, transferrin), antioxidant genes (CAT, SOD), detoxification genes (GST, CYP450) than virgin queens in the Reticulitermes chinensis. In addition, mated kings also highly expressed these genes, except for termicin, transferrin, GST, and CYP450. After mating, both queens and kings significantly upregulated the expression of DNA repair genes (MLH1, BRCA1, XRCC3, RAD54-like). Mismatch repair genes (MMR) MSH2, MSH4, MSH6 were considerably increased in mated queens, while MSH4, MSH5, MSH6 were upregulated in mated kings. Our results suggest that mating increases the expression of immune and DNA repair genes in the termite queens and kings, and thus possibly improving their survival during reproductive span due to the omnipresent pathogens.

Molecular Modeling and Synthesis of Indoline-2,3-dione-Based Benzene Sulfonamide Derivatives and Their Inhibitory Activity against α-Glucosidase and α-Amylase Enzymes.

Diabetes is also known as a critical and noisy disease. Hyperglycemia, that is, increased blood glucose level is a common effect of uncontrolled diabetes, and over a period of time can cause serious effects on health such as blood vessel damage and nervous system damage. However, many attempts have been made to find suitable and beneficial solutions to overcome diabetes. Considering this fact, we synthesized a novel series of indoline-2,3-dione-based benzene sulfonamide derivatives and evaluated them against α-glucosidase and α-amylase enzymes. Out of the synthesized sixteen compounds (1-16), only three compounds showed better results; the IC50 value was in the range of 12.70 ± 0.20 to 0.90 ± 0.10 µM for α-glucosidase against acarbose 11.50 ± 0.30 µM and 14.90 ± 0.20 to 1.10 ± 0.10 µM for α-amylase against acarbose 12.20 ± 0.30 µM. Among the series, only three compounds showed better inhibitory potential such as analogues 11 (0.90 ± 0.10 µM for α-glucosidase and 1.10 ± 0.10 µM for α-amylase), 1 (1.10 ± 0.10 µM for α-glucosidase and 1.30 ± 0.10 µM for α-amylase), and 6 (1.20 ± 0.10 µM for α-glucosidase and 1.60 ± 0.10 µM for α-amylase). Molecular modeling was performed to determine the binding affinity of active interacting residues against these enzymes, and it was found that benzenesulfonohydrazide derivatives can be indexed as suitable inhibitors for diabetes mellitus.

Nuclear and Morphological Alterations in Erythrocytes, Antioxidant Enzymes, and Genetic Disparities Induced by Brackish Water in Mrigal Carp (Cirrhinus mrigala).

Salinization of aquatic ecosystem, abrupt climate change, and anthropogenic activities cause adverse impact on agricultural land/soil as well as the aquaculture industry. This experimental study was designed to evaluate different biomarkers of oxidative stress, antioxidant enzymes, and genotoxic potential of diverse salinities of brackish water on freshwater fish. A total of 84 fresh water mrigal carp (Cirrhinus mrigala) were randomly segregated and maintained in four groups (T0, T1, T2, and T3) in a glass aquarium under similar laboratory conditions at various salinity levels (0, 3, 5, and 7 parts per thousand) to determine the pathological influence of brackish water. All the fish in groups T1, T2, and T3 were exposed to various salinity levels of brackish water for a period of 90 days while the fish of group T0 served as the control group. The experimental fish reared in different groups T1, T2, and T3 displayed various physical and behavioral ailments. The results revealed significantly augmented quantity of different oxidative stress indicators including reactive oxygen species (ROS) and thiobarbituric acid reactive substance (TBARS) in different visceral tissues (kidneys, liver, and gills) of exposed fish. Different antioxidant enzymes such as reduced glutathione (GSH), peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) along with total proteins were remarkably reduced in the kidneys, gills, and liver tissues. Results showed significantly increased values of different nuclear abnormalities (erythrocyte with micronucleus, erythrocyte with condensed nucleus, and erythrocyte with lobed nucleus) and morphological changes (pear shaped erythrocyte, spindle-shaped erythrocytes, and spherocyte) in red blood cells of experimental fish. The results on genotoxic effects exhibited significantly increased DNA damage in isolated cells of liver, kidneys, and gills of exposed fish. The findings of our experimental research suggested that brackish water causes adverse toxicological impacts on different visceral tissues of fresh water fish at higher salinity level through disruption and disorder of physiological and biochemical markers.

Phosphazene Cyclomatrix Network-Based Polymer: Chemistry, Synthesis, and Applications.

Polyphosphazenes are an inorganic molecular hybrid family with multifunctional properties due to their wide range of organic substitutes. This review intends to propose the basics of the synthetic chemistry of polyphosphazene, describing for researchers outside the field the basic knowledge required to design and prepare polyphosphazenes with desired properties. A special emphasis is placed on recent advances in chemical synthesis, which allow not only the synthesis of polyphosphazenes with controlled molecular weights and polydispersities but also the synthesis of novel branched designs and block copolymers. We also investigated the synthesis of polyphosphazenes using various functional materials. This review aims to assist researchers in synthesizing their specific polyphosphazene material with unique property combinations, with the hope of stimulating further research and even more innovative applications for these highly interesting multifaceted materials.

Deciphering the Role of Alkali Metals (Li, Na, K) Doping for Triggering Nonlinear Optical (NLO) Properties of T-Graphene Quantum Dots: Toward the Development of Giant NLO Response Materials.

Nanoscale nonlinear optical (NLO) materials have received huge attention of the scientists in current decades because of their enormous applications in optics, electronics, and telecommunication. Different studies have been conducted to tune the nonlinear optical response of the nanomaterials. However, the role of alkali metal (Li, Na, K) doping on triggering the nonlinear optical response of nanomaterials by converting their centrosymmetric configuration into noncentrosymmetric configuration is rarely studied. Therefore, to find a novel of way of making NLO materials, we have employed density functional theory (DFT) calculations, which helped us to explore the effect of alkali metal (Li, Na, K) doping on the nonlinear optical response of tetragonal graphene quantum dots (TGQDs). Ten new complexes of alkali metal doped TGQDs are designed theoretically. The binding energy calculations revealed the stability of alkali metal doped TGQDs. The NLO responses of newly designed complexes are evaluated by their polarizability, first hyperpolarizability (ßo), and frequency dependent hyperpolarizabilities. The Li@r8a exhibited the highest first hyperpolarizability (ßo) value of 5.19 × 105 au. All these complexes exhibited complete transparency in the UV region. The exceptionally high values of ßo of M@TGQDs are accredited to the generation of diffuse excess electrons, as indicated by NBO analysis and PDOS. NCI analysis is accomplished to examine the nature of bonding interactions among alkali metal atoms and TGQDs. Our results suggest alkali metal doped TGQD complexes as potential candidates for nanoscale NLO materials with sufficient stability and enhanced NLO response. This study will open new doors for making giant NLO response materials for modern hi-tech applications.

Histopathological Investigations and Molecular Confirmation Reveal Mycobacterium bovis in One-Horned Rhinoceros (Rhinoceros unicorns).

Mycobacterium bovis causes tuberculosis in dairy and wild animals. Presence of tuberculosis in animals poses a threat not only to their herd mates but also for public. No reports are available about the clinical, pathological, and molecular investigation of naturally occurring tuberculosis (TB) due to M. bovis in one-horned rhinoceros. One-horned female rhinoceros (Rhinoceros unicorns) at the age of 41 years died in a public park in Pakistan. Postmortem and other investigations were carried out to know the cause of death. The present study describes necropsy, histopathology, and molecular-based confirmation of TB in a captive female rhinoceros that died of this infection. Clinically, the rhinoceros showed nonspecific clinical signs including anorexia, lethargy, dyspnoea, coughing, and sudden death. At necropsy, the trachea exhibited mild congestion and contained catarrhal exudate at the bronchial bifurcation. Macroscopic examination revealed characteristic tubercles on all parenchymatous organs. The lungs showed consolidation, grey hepatization, and contained granulomatous lesions packed with cheesy exudate. Histopathological examination showed severe pneumonic changes in the form of granulomatous inflammation consisting of lymphocytes, multinucleated giant cells, caseous materials, and mineralized foci surrounded by a fibrous capsule. PCR amplicon of 500 bp confirmed the presence of M. bovis in multiple hepatic and pulmonary tissue samples, as well as in uterine exudates. It was concluded that the presence of tuberculosis in rhinoceros may pose potential transmission risk to other animals and the application of practical tools to determine TB status in the rhinoceros is crucial.

Pathological, Histological, and Molecular Based Investigations Confirm Novel Mycobacterium bovis Infection in Boselaphus tragocamelus.

Mycobacterium bovis (M. bovis) being the main cause of animal tuberculosis is a complex infectious agent and can be a cause of zoonotic tuberculosis zoonosis in public health. To date, the uncommon infection in public health due to M. bovis still is a great challenge to both veterinary and medical professions and requires a careful diagnosis and confirmation of the bacterium. Therefore, this study for the first time reports the clinical, gross, histopathological, and molecular based confirmation of M. bovis infection in wildlife animals (nilgai). Prior to death, the morbid animal showed severe pneumonic ailments like moist cough, thick nasal exudates, and dyspnoea. At necropsy, enlargement of mandibular cervical and mesenteric lymph nodes was observed. Different macroscopic lesions such as congestion and hyperaemia, creamy white and catarrhal exudates in trachea, consolidation, grey and red hepatisation of lungs, and micro- and macrogranulomatous tubercles containing caseous materials in lungs were observed. The heart of morbid animal showed congestions, myocarditis, and a copious amount of straw-colored fluid in the pericardial sac. At the microscopic level, lungs indicated granulomatous inflammatory response, presence of multinucleated giant cells, fibrosis, and punctuation of alveoli with chronic inflammatory cells. Histopathological examination of various sections of the heart of the infected animal showed chronic inflammatory response consisting of chronic inflammatory cells like monocyte, lymphocytes, and fibroblasts along with noncalcified eosinophilic materials. At the molecular level, M. bovis infection was confirmed in various tissues like the heart, lungs, cervical, and mesenteric lymph nodes in morbid animals. In conclusion, based on our results, it can be suggested that more molecular based epidemiological studies are crucial to know the exact cause of pulmonary and cervical tuberculosis in wild animals.

Enhanced Healing Activity of Manuka Honey and Nitrofurazone Composite in Full-Thickness Burn Wounds in the Rabbit Model.

Burns cause many significant changes in metabolism and inflammatory reactions, leading to poor regeneration in animals and humans. A list of medicines to treat burns is available in the market. But due to the high cost of these medicines, these are unaffordable, especially for farmers of middle-class families of Africa and Asia. Therefore, a low-cost complementary treatment has always been a topic of many researchers, and there is a dire need of time for the welfare of animals to save them. The current study was planned to scrutinize the therapeutic effects of Manuka honey and Nitrofurazone ointments on full-thickness burn wounds in the rabbit model. The healing efficacy was performed through wound contraction rate, hematological analysis, the thickness of dermis and epidermis, and collagen content percentage. Histopathology was performed after taking biopsy samples at the end of the research. Based on statistical analysis using wound healing time (days, D), the combination (MO + NT) resulted in a shorter period (27 D ± 1) than the average healing time of controlled (36 ± 2), Manuka ointment (31.33 D ± 1.52), and Nitrofurazone ointment (32 ± 1). A significant decrease in the count of red blood cell (RBC), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) in all treatments was noticed mainly in MO + NT. Furthermore, burns induced a significant difference (p < 0.05) in the white blood cells (WBCs) count levels in the MO-treated group. While the level of platelets (PLTs) was not significantly different from the healthy control group. Histopathological assessment (epithelialization, fibrosis, and angiogenesis) of skin showed burn healing to be better in MO and MO + NT groups. In conclusion, the composite of Manuka honey with Nitrofurazone led to the faster recovery than other treatments.

The occurrence of multidrug-resistant Mycobacterium tuberculosis from patients of pulmonary tuberculosis.

INTRODUCTION: Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) is one of the leading causes of death in the world. The resource constraints make it difficult to diagnose and monitor the cases of MDR-TB. GeneXpert is a recognized tool used to diagnose the patients of pulmonary tuberculosis in clinical settings across the globe. METHODOLOGY: The present one-year cross-sectional study was conducted to estimate the occurrence of MDR-TB in patients with pulmonary TB. A total of 1000 patients suspected of pulmonary tuberculosis were included in this study. A random convenient sampling technique was done to collect the sputum samples (twice) from the patients. Samples were processed for the detection of Mycobacterium tuberculosis using conventional detection methods like the Ziehl Nelson staining method and fluorescent microscopy. Additionally, Cepheid GeneXpert was used for molecular detection of MDR-TB in smear-positive samples of pulmonary tuberculosis by amplifying the rifampicin resistance determining region (RRDR; rpoB gene). All the tests were performed in the biosafety level III lab of District Headquarters Hospital Nankana Sahib. RESULTS: It was observed that 103 (10.3%) individuals were diagnosed as positive for tuberculosis among 1000 patients. Among these 103 TB positive cases, there were 11 (10.7%) patients diagnosed with rifampicin resistance gene (RR-Gene) of Mycobacterium tuberculosis. CONCLUSIONS: Overall findings of the study showed that MDR-TB is prevalent in pulmonary TB patients and GeneXpert is the most sensitive technique for early diagnosis of the disease, which may be very helpful in the treatment and control of this public health menace in low and middle-income countries.

Gut-Thyroid axis: How gut microbial dysbiosis associated with euthyroid thyroid cancer.

Thyroid cancer in humans has a fast-growing prevalence, with the most common lethal endocrine malignancy for unknown reasons. The current study was aimed to perform qualitative and quantitative investigation and characterization of the gut bacterial composition of euthyroid thyroid cancer patients. The fecal samples were collected from sixteen euthyroid thyroid cancer patients and ten from healthy subjects. The PCR-DGGE was conducted by targetting the V3 region of 16S rRNA gene, as well as real-time PCR for Bacteroides vulgatus, E.coli Bifidobacterium, Clostridium leptum and Lactobacillus were carried. High-throughput sequencing of V3+V4 region of 16S rRNA gene was performed on Hiseq 2500 platform on 20 (10 healthy & 10 diseased subjects) randomly selected fecal samples. The richness indices and comparative diversity analysis showed significant gut microbial modification in euthyroid thyroid cancer than control. At phylum level, there was significant enrichment of Firmicutes, Verrucomicrobia, while a significant decrease in Bacteroidetes was detected in the experimental group. At family statistics, significant high levels of Ruminococcaceae and Verrucomicrobiaceae, while the significant lower abundance of Bacteroidaceae, Prevotellaceae, Porphyromonadaceae, and Alcaligenaceae was after observed. It also found that the significantly raised level of Escherichia-Shigella, Akkermansia [Eubacterium]_coprostanoligenes, Dorea, Subdoligranulum, and Ruminococcus_2 genera, while significantly lowered genera of the patient group were Prevotella_9, Bacteroides and Klebsiella. The species-level gut microbial composition showed a significantly raised level of Escherichia coli in euthyroid thyroid cancer. Thus, this study reveals that euthyroid thyroid cancer patients have significant gut microbial dysbiosis. Moreover, Statistics (P<0.05) of each gut microbial taxa were significantly changed in euthyroid thyroid cancer patients. Therefore, the current study may propose new approaches to understanding thyroid cancer patients' disease pathways, mechanisms, and treatment.

Hematobiochemical, Oxidative Stress, and Histopathological Mediated Toxicity Induced by Nickel Ferrite (NiFe2O4) Nanoparticles in Rabbits.

From the past few decades, attention towards the biological evaluation of nanoparticles (NPs) has increased due to the persistent and extensive application of NPs in various fields, including biomedical science, modern industry, magnetic resonance imaging, and the construction of sensors. Therefore, in the current study, magnetic nickel ferrite (NiFe2O4) nanoparticles (NFNPs) were synthesized and evaluated for their possible adverse effects in rabbits. The crystallinity of the synthesized NFNPs was confirmed using X-ray diffraction (XRD) technique. The saturation magnetization (46.7 emug-1) was measured using vibrating sample magnetometer (VSM) and 0.35-tesla magnetron by magnetic resonance imaging (MRI). The adverse effects of NFNPs on blood biochemistry and histoarchitecture of the liver, kidneys, spleen, brain, and heart of the rabbits were determined. A total of sixteen adult rabbits, healthy and free from any apparent infection, were blindly placed in two groups. The rabbits in group A served as control, while the rabbits in group B received a single dose (via ear vein) of NFNPs for ten days. The blood and visceral tissues were collected from each rabbit at days 5 and 10 of posttreatment. The results on blood and serum biochemistry profile indicated significant variation in hematological and serum biomarkers in NFNP-treated rabbits. The results showed an increased quantity of oxidative stress and depletion of antioxidant enzymes in treated rabbits. Various serum biochemical tests exhibited significantly higher concentrations of different liver function tests, kidney function tests, and cardiac biomarkers. Histopathologically, the liver showed congestion, edema, atrophy, and degeneration of hepatocytes. The kidneys exhibited hemorrhages, atrophy of renal tubule, degeneration, and necrosis of renal tubules, whereas coagulative necrosis, neutrophilic infiltration, and severe myocarditis were seen in different sections of the heart. The brain of the treated rabbits revealed necrosis of neurons, neuron atrophy, and microgliosis. In conclusion, the current study results indicated that the highest concentration of NPs induced adverse effects on multiple tissues of the rabbits.

Residue of thiram in food, suppresses immune system stress signals and disturbs sphingolipid metabolism in chickens.

Thiram, a well-known sulfur containing organic compound is frequently and extensively used in agriculture because of high biological activity to control different pests. In certain cases, due to long persistence in the environment pesticides and other environmental contaminants induce undesirable toxic impacts to public health and environment. To ascertain the potential mechanisms of toxicity of thiram on different immune organs of broilers, a total of 100 one-day-old chicks were obtained and randomly divided into two groups including thiram group (50 mg/kg) and untreated control group. Thymus and spleen tissues were collected at the age of 14 days from the experimental birds. At necropsy level, thymus was congested, enlarged and hyperemic while spleen had no obvious lesions. The results on mechanisms (apoptosis and autophagy) of immunotoxicity showed significantly increased expression of bax, caspase3, cytc, ATG5, beclin1 and p62 in spleen of treated mice. Results indicated significantly decreased expression of m-TOR and bcl2 to activate apoptosis and autophagy. The expressions of bax, p53 and m-TOR were up-regulated in the thymus while the expressions of ATG5 and Beclin1 were down-regulated to mediate cell apoptosis and inhibit autophagy. The results on different metabolome investigation showed that the sphingolipid metabolism in the thymus of chicks exposed to thiram was disrupted resulting in up-regulation of metabolites related to cell membrane components such as SM, galactosylceramide and lactosylceramide. The results of our experimental research suggest that thiram can interfere with the sphingolipid metabolism in thymus and angiogenesis, inhibit the proliferation of vascular endothelial cells to induce potential toxic effects in chicken.

Fabrication of Bimetallic Cu-Ag Nanoparticle-Decorated Poly(cyclotriphosphazene-co-4,4'-sulfonyldiphenol) and Its Enhanced Catalytic Activity for the Reduction of 4-Nitrophenol.

We reported a study on the preparation of bimetallic Ag-Cu nanoparticles (NPs) impregnated on PZS poly(cyclotriphosphazene-co-4,4'-sulfonyldiphenol) nanotubes via a facile and efficient reduction method. Herein, PZS nanotubes consisting of enriched hydroxyl groups are fabricated through an in situ template method, and then, fluctuating the amount ratios of Cu and Ag precursors, bimetallic NPs can be fabricated on readily prepared PZS nanotubes using NaBH4 as a reductant, which results in a series of bimetallic catalysts having tunable catalytic activity. The characterization investigations of scanning electron microscopy, X-ray diffraction, transmission electron microscopy, and Fourier transform infrared spectroscopy results show that Ag-Cu bimetallic NPs are well-dispersed, ultrasmall in size, and well-anchored on the surface of PZS nanotubes. In addition, to examine the catalytic activity and reusability of these nanocomposites, reduction of 4-nitrophenol to 4-aminophenol is utilized as a prototype reaction. The optimized Ag-Cu NPs with a copper ratio of 0.3% are well-stabilized by the organic-inorganic poly(cyclotriphosphazene-co-4,4'-sulfonyldiphenol) nanotubes. The obtained results show that bimetallic NPs have remarkably higher catalytic ability than that of their monometallic counterparts with maximum catalytic activity. These results are even better than those of noble metal-based bimetallic catalysts and pave the avenue to utilize the polyphosphazene polymer as a substrate material for highly effective bimetallic catalysts.

The potential role of dietary plant ingredients against mammary cancer: a comprehensive review.

Breast cancer is known as the most devastating cancer in the global female community and is considered as one of the severe health care burdens in both developed and developing countries. In many cases, breast cancer has shown resistance to chemotherapy, radiotherapy and hormonal therapy. Keeping in view these limitations, there is an urgent need to develop safe, readily available and effective breast anticancer treatments. Therefore, the scientists are keen in the extraction of plant-based phytochemicals (organosulfur compounds, betalains, capsaicinoids, terpenes, terpenoids, polyphenols, and flavonoids) and using them as breast anticancer agents. Results of numerous epidemiological investigations have revealed the promising role of phytochemicals in the prevention and treatment of breast cancer. The diverse classes of plant bioactive metabolites regulate different metabolic and molecular processes, which can delay the proliferation of cancers. These phytochemicals possess chemo-preventive properties as they down-regulate the expression of estrogen receptor-α, inhibit the proliferation of cancer cells, and cause cell cycle arrest by inducing apoptotic conditions in tumor cells. This review article discusses the potent role of various plant-based phytochemicals as potential therapeutic agents in the treatment or prevention of breast cancer along with the proposed mechanisms of action.

Gut microbial dysbiosis and its association with esophageal cancer.

Due to its aggressive nature and low survival rate, esophageal cancer is one of the deadliest cancer. While the intestinal microbiome significantly influences human health and disease. This research aimed to investigate and characterize the relative abundance of intestinal bacterial composition in esophageal cancer patients. The fecal samples were collected from esophageal cancer patients (n = 15) and healthy volunteers (n = 10). The PCR-DGGE was carried out by focusing on the V3 region of the 16S rRNA gene, and qPCR was performed for Bacteroides vulgatus, Escherichia coli, Bifidobacterium, Clostridium leptum and Lactobacillus. High-throughput sequencing of the 16S rRNA gene targeting the V3+V4 region was performed on 20 randomly selected samples. PCR-DGGE and High-throughput diversity results showed a significant alteration of gut bacterial composition between the experimental and control groups, which indicates the gut microbial dysbiosis in esophageal cancer patients. At the phylum level, there was significant enrichment of Bacteroidetes, while a non-significant decrease of Firmicutes in the experimental group. At family statistics, a significantly higher level of Bacteroidaceae and Enterobacteriaceae, while a significantly lower abundance of Prevotellaceae and Veillonellaceae were observed. There was a significantly high prevalence of genera Bacteroides, Escherichia-Shigella, while a significantly lower abundance of Prevotella_9 and Dialister in the experimental group as compared to the control group. Furthermore, the species analysis also showed significantly raised level of Bacteroides vulgatus and Escherichia coli in the experimental group. These findings revealed a significant gut microbial dysbiosis in esophageal cancer patients. So, the current study can be used for the understanding of esophageal cancer treatment, disease pathway, mechanism, and probiotic development.

Coumaronochromone as antibacterial and carbonic anhydrase inhibitors from Aerva persica (Burm.f.) Merr.: experimental and first-principles approaches.

The Aerva plants are exceptionally rich in phytochemicals and possess therapeutics potential. Phytochemical screening shows that Aerva persica (Burm.f.) Merr. contains highest contents i.e., total phenolics, flavonoids, flavonols, tannins, alkaloids, carbohydrates, anthraquinones and glycosides. In-vitro antibacterial and enzymatic (carbonic anhydrase) inhibition studies on methanol extracts of A. persica indicated the presence of biological active constituents within chloroform soluble portions. Investigation in the pure constituents on the chloroform portions of A. persica accomplished by column chromatography, NMR and MS analysis. The bioguided isolation yields four chemical constituents of coumaronochromone family, namely aervin (1-4). These pure chemical entities (1-4) showed significant antibacterial activity in the range of 60.05-79.21 µg/ml against various bacterial strains using ampicillin and ciprofloxacin as standard drugs. The compounds 1-4 showed promising carbonic anhydrase inhibition with IC50 values of 19.01, 18.24, 18.65 and 12.92 µM, respectively, using standard inhibitor acetazolamide. First-principles calculations revealed comprehensive intramolecular charge transfer in the studied compounds 1-4. The spatial distribution of highest occupied and lowest unoccupied molecular orbitals, ionization potential, molecular electrostatic potential and Hirshfeld analysis revealed that these coumaronochromone compounds would be proficient biological active compounds. These pure constituents may be used as a new pharmacophore to treat leaukomia, epilepsy, glaucoma and cystic fibrosis.