Melatonin is a well-known potent endogenous antioxidant pharmacological agent with significant neuroprotective actions. Here in the current study, we explored the nuclear factor erythroid 2-related ...factor 2 (Nrf2) gene-dependent antioxidant mechanism underlying the neuroprotective effects of the acute melatonin against acute ethanol-induced elevated reactive oxygen species (ROS)-mediated neuroinflammation and neurodegeneration in the developing rodent brain.
In vivo rat pups were co-treated with a single dose of acute ethanol (5 g/kg, subcutaneous (S.C.)) and a single dose of acute melatonin (20 mg/kg, intraperitoneal (I.P.)). Four hours after a single S.C. and I.P. injections, all of the rat pups were sacrificed for further biochemical (Western blotting, ROS- assay, LPO-assay, and immunohistochemical) analyses. In order to corroborate the in vivo results, we used the in vitro murine-hippocampal HT22 and microglial BV2 cells, which were subjected to knockdown with small interfering RNA (siRNA) of Nrf2 genes and exposed with melatonin (100 μM) and ethanol (100 mM) and proceed for further biochemical analyses.
Our biochemical, immunohistochemical, and immunofluorescence results demonstrate that acute melatonin significantly upregulated the master endogenous antioxidant Nrf2 and heme oxygenase-1, consequently reversing the acute ethanol-induced elevated ROS and oxidative stress in the developing rodent brain, and in the murine-hippocampal HT22 and microglial BV2 cells. In addition, acute melatonin subsequently reduced the activated MAPK-p-P38-JNK pathways and attenuated neuroinflammation by decreasing the expression of activated gliosis and downregulated the p-NF-
-B/p-IKKβ pathway and decreased the expression levels of other inflammatory markers in the developing rodent brain and BV2 cells. Of note, melatonin acted through the Nrf2-dependent mechanism to attenuate neuronal apoptosis in the postnatal rodent brain and HT22 cells. Immunohistofluorescence results also showed that melatonin prevented ethanol-induced neurodegeneration in the developing rodent brain. The in vitro results indicated that melatonin induced neuroprotection via Nrf2-dependent manner and reduced ethanol-induced neurotoxicity.
The pleiotropic and potent neuroprotective antioxidant characteristics of melatonin, together with our in vivo and in vitro findings, suppose that acute melatonin could be beneficial to prevent and combat the acute ethanol-induced neurotoxic effects, such as elevated ROS, neuroinflammation, and neurodegeneration in the developing rodent brain.
In the present investigation, ZnO NPs was fabricated using Eriobotrya japonica leaves extract. The E. Japonica leaves powder was extracted and mixed with 0.2 M zinc nitrate in 2:4 ratio and pH was ...adjusted using ammonia solution. Different techniques including UV–Visible spectroscopy (U.V-Vis), X-ray diffraction (XRD), Energy dispersive X-ray (EDX), Fourier transform infrared (FTIR) and Scanning electron microscope (SEM) techniques were employed to characterize the synthesized ZnO NPs. The peak at 375 nm was observed for ZnO NPs, while the average particle size was 13.0 nm. The elemental composition analysis revealed the NPs was highly pure having irregular platelets shape with aggregates tendency. The as-prepared ZnO NPs was analyzed for their photocatalytic, antibacterial and antioxidant properties. The ZnO NPs exhibited a promising DPPH scavenging activity and was highly active against S. aureus, P. multocida, E. coli and B. subtilis strains. The photocatalytic activity (PCA) was appraised against the removal of methylene blue (MB) dye and we found 72% degradation within 160 min of treatment. Since the synthesized NPs have shown promising bioactivity and PCA, the synthesis of these NPs using E. japonica leaves extracts is suggested for different applications.
The poultry industry in developing countries is still combating mortality and economic loss due to Salmonella contamination. Salmonella Gallinarum is a common pathogen of poultry birds, being the ...etiologic agent of fowl typhoid, which specifically infects adult birds via the oral-fecal route. Timely detection of S. Gallinarum in poultry flocks can allow early treatment intervention leading to a decrease in economic losses. Detection of S. Gallinarum is challenging, while its PCR-based detection is a promising strategy, however, due to its high genomic similarity with other commonly existing Salmonella spp., identification of S. Gallinarum from poultry samples with high specificity is still a challenge. The current study was conducted to isolate S. Gallinarum from different districts of Pakistan, assess their antibiotic susceptibility profile, and develop a method for its early detection. A total of 20 strains were isolated using buffer peptone water, selenite cysteine broth, and Xylose Lysine Tergitol-4 (XLT-4) agar supplemented with tergitol and characterized by biochemical procedures. The antibiotic sensitivity profile highlighted the highest resistance of isolates towards novobiocin and nalidixic acid, commonly used antibiotics in Pakistan Poultry production. The primers designed to amplify a unique genomic region of S. Gallinarum, showed successful detection of twenty S. Gallinarum strains, while no amplification with genomic DNA from other common Salmonella spp. The reported method can be utilized to detect S. Gallinarum from tissue samples of infected birds in a short time leading to early diagnosis and timely treatment intervention.
•Salmonella Gallinarum is host specific, etiologic agent of fowl typhoid.•Fowl typhoid results in a massive loss of poultry flocks due to high mortality.•Primer sets designed against a unique region of S. Gallinarum make quick and accurate detection of bacteria even directly from infected tissue samples.
Total 23 algal species belonging to 14 genera were reported from different sites of district Lahore. They were collected from freshwater of some areas of Lahore city during October 2017 to March ...2018. All were taxonomically investigated up to specie level using light microscopy (LM). Following species were identified: Achanthes hungarica (Grunow) Grunow in Cleve et Grunow 1880, Achnanthes minutissima (Kützing) Cleve, Anabaena affinis Lemmermann, Aphanothece endophytica G.M. Smith, Aphanothece nidulans P. Richter, Calothrix fusca (Kützing) Bornet & Flahault, Chroococcus limenticus var. distans G.M. Smith, Chroococcus minor (Kützing) Lemmermann, Cyclotella operculata (C.A. Agardh) Brebisson, Cymbella ehrengbergii Kützing, Cymbella turgida, Lyngbya arboricola Bruhlet Bruh, Lyngbya tylorii Drouet & Strickland, Navicula confervacea (Kützing) Grun. var. confervacea, Navicula knsnesis Meister, Oedogonium behemicum Hirn, Oscillatoria amoena (Kützing) Gomont, Oscillatoria amphibia C. Agardh ex Gomont, Oscillatoria subbrevis Schmidle, Pinuularia interrupta W. Smith, Spirulina subsala (Oersted) ex Gomont, Ulothrix aequalis Kützing, Ulothrix tenuissima Kützing.
The research was planned to study:
the diversity of algal species of various selected areas of Lahore
light microscopy was used to determine the morphological and anatomical characters
It was concluded that species varies as altitude varies and their anatomical changes also been observed using LM.
Chronic neuroinflammation is responsible for multiple neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Lipopolysaccharide (LPS) is an essential ...component of the gram-negative bacterial cell wall and acts as a potent stimulator of neuroinflammation that mediates neurodegeneration. Quercetin is a natural flavonoid that is abundantly found in fruits and vegetables and has been shown to possess multiple forms of desirable biological activity including anti-inflammatory and antioxidant properties. This study aimed to evaluate the neuroprotective effect of quercetin against the detrimental effects of LPS, such as neuroinflammation-mediated neurodegeneration and synaptic/memory dysfunction, in adult mice. LPS 0.25 mg/kg/day, intraperitoneally (I.P.) injections for 1 week-induced glial activation causes the secretion of cytokines/chemokines and other inflammatory mediators, which further activate the mitochondrial apoptotic pathway and neuronal degeneration. Compared to LPS alone, quercetin (30 mg/kg/day, I.P.) for 2 weeks (1 week prior to the LPS and 1 week cotreated with LPS) significantly reduced activated gliosis and various inflammatory markers and prevented neuroinflammation in the cortex and hippocampus of adult mice. Furthermore, quercetin rescued the mitochondrial apoptotic pathway and neuronal degeneration by regulating Bax/Bcl2, and decreasing activated cytochrome c, caspase-3 activity and cleaving PARP-1 in the cortical and hippocampal regions of the mouse brain. The quercetin treatment significantly reversed the LPS-induced synaptic loss in the cortex and hippocampus of the adult mouse brain and improved the memory performance of the LPS-treated mice. In summary, our results demonstrate that natural flavonoids such as quercetin can be beneficial against LPS-induced neurotoxicity in adult mice.
•JKP2 is a first isolated phage against Klebsiella K-17 capsular serotype.•It produced bulls eye shaped clear lytic plaques due to tail associated depolymerase.•JKP2 remained stable at tested pH (5 ...to 10) and temperatures (37 to 60 °C).•JKP2 showed K. pneumoniae biofilm reduction potential.•Based on whole genome sequence analysis it belong to unclassified Drulisvirus within the Autographiviridae family.
Klebsiella pneumoniae is an opportunistic pathogen responsible for nearly one-third of all Gram-negative infections. Increasing antibiotic resistance has pushed scientists to look for alternative therapeutics. Bacteriophages have emerged as one of the promising alternatives. In the current study, the Klebsiella phage JKP2 was isolated from a sewage sample and characterized against the K-17 serotype of K. pneumoniae. It produced bulls-eye-shaped clear plaques and has a latent period of 45 min with a burst size of 70 pfu/cell. It remained stable at tested pH (5 to 10) and temperatures (37 to 60 °C). Its optimum temperature for long-term storage is 4 °C and -80 °C. The JKP2 showed its infectivity against the K. pneumoniae K-17 serotype only. It controlled planktonic cells of K. pneumoniae 12 h post-incubation. At MOI-1, it efficiently eliminated 98% of 24 and 96% of 48-hour-old biofilm and 86% and 82% of mature biofilm of day 3 and 4, respectively. The JKP2 has an icosahedral capsid of 54 ± 0.5 nm with a short, non-contractile tail, measuring 12 ± 0.2 nm. It possesses a double-stranded DNA genome of 43.2 kbp with 54.1% GC content and encodes 54 proteins, including 29 with known functions and 25 with unknown functions. JKP2 was classified as Drulisvirus within the Autographiviridae family. It uses a T7-like direct terminal repeat strategy for genome packaging. JKP2 can be applied safely for therapeutic purposes as it does not encode an integrase or repressor genes, antibiotic resistance genes, bacterial virulence factors, and mycotoxins.
In this work, a series of eight different bipolar molecules were designed and calculated using density functional theory (DFT) and time‐dependent functional theory (TD‐DFT) for organic light emitting ...diodes (OLEDs) as efficient luminescent and charge transfer materials. The eight donor‐π‐donor type small molecules (D1‐D8) were composed of triphenylamine (TPA) donor (D) unit connected to 1,8‐naphthalimides (NI) acceptor (A) unit though different π‐conjugated or R‐groups (as π‐spacer). The effect of substitutions made in π‐spacer was investigated on optical, electronic, and stability properties. This calculation analysis showed that different substitutions in π‐spacer resulted smaller Eg (range from 1.63 to 2.00 eV), broader absorption with the lowest excitation energy covering both visible and near infrared regions of solar spectrum, especially D3, D4, D5, and D6 molecules. The analyses of local densities of states, frontier molecular orbitals, and natural population analysis of orbitals revealed that studied molecules exhibited π‐π* electronic transitions of absorption in singlet excited states, but D5 and D6 also show intramolecular charge transfer (ICT) characteristics. The study of chemical indices, molecular electrostatic potential (MEP) surfaces, and charge transfer properties turned out that D4, D5, and D6 are expected to show good potential for luminescent and hole transport materials in the favor of OLEDs.
Schematic chemical structures and stimulated absorption spectra of investigated D1 to D8 donor molecules.
Context and motivation: Cyber-Physical Systems (CPSs) are gaining priority over other systems. The heterogeneity of these systems increases the importance of security. Both the developer and the ...requirement analyst must consider details of not only the software, but also the hardware perspective, including sensor and network security. Several models for secure software engineering processes have been proposed, but they are limited to software; therefore, to support the processes of security requirements, we need a security requirements framework for CPSs. Question/Problem: Do existing security requirements frameworks fulfil the needs of CPS security requirements? The answer is no; existing security requirements frameworks fail to accommodate security concerns outside of software boundaries. Little or even no attention has been given to sensor, hardware, network, and third party elements during security requirements engineering in different existing frameworks. Principal Ideas/results: We have proposed, applied, and assessed an incremental security requirements evolution approach, which configures the heterogeneous nature of components and their threats in order to generate a secure system. Contribution: The most significant contribution of this paper is to propose a security requirements engineering framework for CPSs that overcomes the issue of security requirements elicitation for heterogeneous CPS components. The proposed framework supports the elicitation of security requirements while considering sensor, receiver protocol, network channel issues, along with software aspects. Furthermore, the proposed CPS framework has been evaluated through a case study, and the results are shown in this paper. The results would provide great support in this research direction.
PurposeThe purpose of the study is to map the funding status of COVID-19 research. The various aspects, such as funding ratio, geographical distribution of funded articles, journals publishing funded ...research and institutions that sponsor the COVID-19 research are studied. To visualize the country collaboration network and research trends/hotspots in the field of COVID-19 funded research, keyword analysis is also performed. The open-access (OA) status of the funded research on COVID-19 is also discussed.Design/methodology/approachThe leading indexing and abstracting database, i.e. Web of Science (WoS), was used to retrieve the funded articles published on the topic COVID-19. The scientometric approach, more particularly “funding acknowledgment analysis (FAA),” was used to study the research funding.FindingsA total of 5,546 publications of varied nature have been published on COVID-19, of which 1,760 are funded, thus indicating a funding ratio of 32%. China is the leading producer of funded research (760, 43.182%) on COVID-19 followed by the USA (482, 27.386%), England (179, 10.17%), Italy (119, 6.761%), Germany (107, 6.08%) and Canada (107, 6.08%). China is also in lead in terms of the funding ratio (60.94%). However, the funding ratio of the USA (31.54%) is at 11th rank behind Canada (40.68%), Germany (34.18%) and England (35.87%). The USA occupies a central position in the collaboration network having the highest score of articles with other countries (n = 489), with the USA–China collaboration ranking first (n = 123). National Natural Science Foundation of China (NSFC) is the largest source of funding for COVID-19 research, supporting 342 (19.432%) publications, followed by the United States Department of Health Human Services (DHHS) and National Institute of Health (NIH), USA with 211 (11.989%) and 200 (11.364%) publications, respectively. However, China's National Key Research and Development Program achieves the highest citation impact (80.24) for its funded publications. Journal of Medical Virology, Science of the Total Environment and EuroSurveillance are the three most prolific journals publishing 63 (3.58%), 35 (1.989%) and 32 (1.818%), respectively, of the sponsored research articles on the COVID-19. A total of 3,138 institutions produce funded articles with Huazhong University of Science Technology and Wuhan University from China at the forefront publishing 92 (5.227%) and 83 (4.716%) publications, respectively. The funded research on COVID-19 is largely available in OA mode (1,674, 95.11%) and mainly through the Green and Bronze routes. The keyword clustering reveals that the articles mainly focus on the impact, structure and clinical characteristics of the virus.Research limitations/implicationsThe study's main limitation is that the results are based on the publications indexed by WoS, which has limited coverage compared to other databases. Moreover, all the funding agencies do not require or authors miss to acknowledge funding sources in their publications, which ultimately undermines the number of funded publications. The research publications on COVID-19 are also proliferating; thus, the study's findings shall be valid for a minimum period.Practical implicationsThe funding of research on the COVID-19 is highly essential to accelerate innovative research and help countries fight against the global pandemic. The study's findings reflect the efforts made by nations and institutions to remove the financial and accessibility hurdles. It not only underscores the lead of the USA in the research on COVID-19, but also shows China as a forerunner in sponsoring the research, thus, helping to know the contribution of nations toward understanding the dynamics of pandemic and controlling it. The study will help healthcare practitioners and policymakers recognize the areas that remain the focus of sponsored research on COVID-19 and other left-out areas that need to be taken up and thus may help in policy formulation. It further highlights the impact of prolific funding agencies so that efforts may be initiated to increase the impact and thereby the returns of investment. The study can help to map the scientific structure of COVID-19 through the lens of funded research and recognize core inclinations of its development. Overall, a comprehensive analysis has been performed to present the detailed characteristics of sponsored research on emerging area of COVID-19, and it is informative, useful and one of its kind on the theme.Originality/valueThe study explores the funding support of research on COVID-19 and its other aspects, along with the mode of availability.
A well‐known process, called the advanced oxidation process, has been effectively used to study the oxidation mechanism of pharmaceutical wastes. The strong reactivity of hydroxyl radicals used in ...this process gradually oxidizes organic molecules into nontoxic products. Hence, the mechanistic details of secnidazole, 1‐(2‐hydroxypropy1)‐2‐methy1‐5‐nitroimidazole, oxidation, promoted by •OH have been studied under the M06‐2X method and 6‐311 G (d,p) level of theory, using density functional theory. Secnidazole molecule has been decomposed by oxidation of the isopropanol to an –COOH group, resulting in (2‐methyl‐5‐nitro‐imidazol‐1‐yl) acetic acid, which is further oxidized to (5‐hydroxy‐2‐methylimidazol‐1‐yl) acetic acid, by the action of •OH. Furthermore, nitro and methyl groups present as substituents to the five‐membered ring are replaced by hydroxyl groups, forming 1‐(2‐hydroxypropyl)‐2‐methyl‐1H‐imidazol‐5‐ol and 1‐(2‐hydroxypropyl)‐5‐nitro‐1H‐imidazol‐2‐ol, respectively. The optimized geometries of intermediates, transition states, and free energy surfaces have been found valuable in interpreting the details of the elimination mechanism. Fukui functional analysis has disclosed the reactivities of each site of SNZ. The systematic calculations on initial products and intermediates have shown significant exothermic properties.
The degradation reaction of SNZ with hydroxyl radical has been studied using density functional theory and PCM/M06‐2X/6‐311G(d,p) level of theory. The Fukui functional analysis has shown that the C‐3 attached to the methyl group is the most active site for hydroxyl radical attack. The elimination of methyl or nitro group and oxidation of alcohol group during degradation of secnidazole is exothermic and spontaneous reactions.