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The structural stability, spin-polarized electronic and transport properties of edge-hydrogenated zigzag boron nitride nanoribbons (ZBNNRs) are investigated using density functional theory (DFT) combined with a non-equilibrium Green’s function (NEGF) approach. The considered structures are observed to be energetically stable in the magnetic ground state. The calculated spin-dependent transport properties indicate that a selective-edge hydrogenated ZBNNR device shows bipolar spin filter characteristics. Interestingly, high spin giant magnetoresistance (GMR) and a rectification ratio (RR) are observed of the order of 1015 and 1010, respectively. The observed GMR and rectification behavior in edge-hydrogenated ZBNNRs have potential applications for designing future spintronic nanodevices.

Neurodegenerative disorders occur when nerve cells in the brain or peripheral nervous system partial or complete fail in their functions and sometimes even die due to some injuries or aging. Neurodegenerative disorders such as Alzheimer's Disease (AD) and Parkinson's Disease (PD), have been majorly resulted due to degeneration of neurons and neuroinflammation progressively. There are many similarities that correlates both AD and PD on a cellular and sub-cellular level. Therefore, a hope for therapeutic advancement for simultaneous upgradation in both the diseases are directly depending on the discovery of common mechanism at molecular and cellular level. Recent and past evidences from scientific literature supporting the efficacy of plants flavonoids in treatment and protection of both AD and PD. Further, dietary flavones, specially Heptamethoxyflavone, Kaempferitrin, Vitexin and Amentoflavone gains recently much more attention for producing many health beneficiary effects including neuroprotection. Despite of these evidence a detailed updated overview of neuroprotective effects against both AD and PD by Heptamethoxyflavone, Kaempferitrin, Vitexin and Amentoflavone are still missing. In this context several published studies were assessed by using various online electronic search engines/databases to meet the objective from 1981 to 2021 (Approx. 224). Therefore, present review was designed to deliver the detailed description on these flavones including therapeutic benefits in AD, PD and other CNS complications with critical analysis on underlying mechanisms.

The aim of the present study is to evaluate the neuroprotective effect of methanol extract of Garcinia morella Desr leaves in monosodium glutamate (MSG) induced neurotoxicity in rats. The MSG 2 g/kg, i.p. was used to induce the neurotoxicity. The rats were administrated with methanol extract of Garcinia morella Desr leaves (MEGM) 200 and 400 mg/kg, p.o. and Dextromethorphan 30 mg/kg, p.o. after 1 h injection of MSG. The animals were evaluated for its behavioural factors such as muscle grip and locomotor activity. At the end of the study, the antioxidant enzymes levels, neurotransmitter levels, TNFα, ß-amyloid and mineral levels were estimated in brain homogenate. The MEGM treated group shows significant improvement of behavioural and locomotor activity and muscle strength against MSG induced neurotoxicity. The glutathione, SOD, catalase and total protein levels were significantly increased in MEGM treated group. However, significant reduction within the level of varied neurotransmitters like AChE, Dopamine, TNFα, ß-amyloid were observed on treatment with MEGM extract. Further, MEGM also significantly decrease the MSG induced toxicity through declined levels of Ca+2 and Na+ with increased levels of K+. In conclusion, the present study suggests that the MEGM has significant neuroprotective activity against MSG induced neurotoxic rats.

Activation of invariant natural killer T (iNKT) cells by α-galactosylceramides (α-GalCers) stimulates strong immune responses and potent anti-tumor immunity. Numerous modifications of the glycolipid structure have been assessed to derive activating ligands for these T cells with altered and potentially advantageous properties in the induction of immune responses. Here, we synthesized variants of the prototypical α-GalCer, KRN7000, with amide-linked phenyl alkane substitutions on the C4″-position of the galactose ring. We show that these variants have weak iNKT cell stimulating activity in mouse models but substantially greater activity for human iNKT cells. The most active of the C4″-amides in our study showed strong anti-tumor effects in a partially humanized mouse model for iNKT cell responses. In silico analysis suggested that the tether length and degree of flexibility of the amide substituent affected the recognition by iNKT cell antigen receptors of the C4″-amide substituted glycolipids in complex with their antigen presenting molecule CD1d. Our findings establish the use of stable C4″-amide linked additions to the sugar moiety for further exploration of the immunological effects of structural modifications of iNKT cell activating glycolipids and highlight the critical need for more accurate animal models to assess these compounds for immunotherapeutic potential in humans.

The most popular method for production of metallic uranium is by magnesiothermic reduction of UF4. Efficient production of good quality uranium metal chunk in the reaction vessel requires multiple parameter constraints. To theoretically optimize these process parameters, many basic properties, i.e. particle size, heat dissipation, packing density, heating rate, kinetic parameters of reaction, etc., are required. There was lack of information on kinetic parameters of this reaction; therefore, kinetic triplets of UF4 and magnesium metal reaction were determined by non-isothermal DTA method, at 5–20 K min−1 heating rates. The analysis of data was done by model-less methods and model-fitting methods. It was found that the reaction takes place through two parallel competitive mechanisms, bulk diffusion and first-order nucleation and growth of reaction sites, and the corresponding kinetic parameters, frequency factors and activation energies, were 440 min−1, 43.9 kJ mol−1, 420 min−1 and 49.03 kJ mol−1, respectively.

The thin-layer chromatographic (TLC) analysis of extracts/compounds has several applications in the field of food, cosmetics, phytochemistry, and pharmaceutical industry. Mangiferin is a bioactive and natural antioxidant polyphenolic xanthone obtained from different dietary plants and recently gaining remarkable attention due to its high pharmacological significance evident in current scientific validations. This review contains various TLC methods reported so far for the qualitative and quantitative assessments of mangiferin after collating selected research papers from online scientific databases as PubMed, Web of Science, and Scopus. In particular, confirmation of mangiferin from dietary plant, herbal formulations, and biological and bioautographic samples through TLC are discussed in detail and comparison is also established in terms of selectivity, sensitivity, and validity. Ultimately, critical evaluation was done with the aim to deliver useful suggestions for the selection of suitable mobile phase, sample preparation, and detection methods for the analysis of mangiferin.

Mycobacterium tuberculosis, responsible for Tuberculosis (TB), remains the leading cause of mortality among infectious diseases worldwide from a single infectious agent, with an estimated 1.7 million deaths in 2016. Biotin is an essential cofactor in M. tuberculosis that is required for lipid biosynthesis and gluconeogenesis. M. tuberculosis relies on de novo biotin biosynthesis to obtain this vital cofactor since it cannot scavenge sufficient biotin from a mammalian host. The biotin biosynthetic pathway in M. tuberculosis has been well studied and rigorously genetically validated providing a solid foundation for medicinal chemistry efforts. This review examines the mechanism and structure of the enzymes involved in biotin biosynthesis and ligation, summarizes the reported genetic validation studies of the pathway, and then analyzes the most promising inhibitors and natural products obtained from structure-based drug design and phenotypic screening.

With the free and full access to images from Sentinel-2 satellite, the interest to use this data for quantitative retrieval of vegetation parameters is ever-increasing. LAI and chlorophyll are two key variables which are desired for studying productivity, nutrient and stress status of vegetation. Studies carried out on croplands using simulated Sentinel-2 MSI and parametric approach have identified vegetation indices (VIs) with high sensitivity to LAI and chlorophyll. To test how Sentinel-2 red-edge based VIs perform for retrieval of LAI and Chlorophyll of tropical mixed forest canopies, this study has been performed. The field measurements of LAI and chlorophyll content were recorded in a total of 28 ESUs (Elementary Sampling Units) in Bhakra range in the Tarai Central Forest Division, Uttarakhand (India). The in-situ measurements were statistically correlated with Sentinel-2VIs and strength of correlation was validated using Predicted Residual Error Sum of Squares (PRESS) statistic. Field LAI corrected for foliage clumpiness effect improved correlation of VIs with LAI. Among all VIs tested, Normalized Difference Index (NDI) offered highest positive correlation (R2 = 0.79, p

Electromagnetic safeguards are key factors for electronic devices. Lightweight and highly flexible polymer composite films with high electrical conductivity are considered to be efficient electromagnetic interference (EMI) shielding materials. Polymer composites offer alternative to metal-based composites which have poor flexibility, corrodibility, and are difficult to process. Here, highly flexible polyvinyl alcohol/poly (3, 4-ethylenedioxythiophene):polystyrene sulfonate/multiwalled carbon nanotube (PVA/PEDOT:PSS/MWCNT) free-standing composite films were fabricated by a solution mixing process followed by a simple solvent casting technique. PVA/PEDOT:PSS/MWCNT composite films of thickness around 20 microns showed high EMI shielding effectiveness (SE) in the X-band over the frequency range of 8–12 GHz. Incorporation of MWCNT into the polymer matrix considerably increased the mechanical strength of the PVA/PEDOT:PSS/MWCNT composite free-standing film. This investigation revealed that PVA/PEDOT:PSS/MWCNT composite film with 0.5 wt.% of MWCNT showed excellent absorption-dominated EMI SE of 60 dB over the frequency range of 8–12 GHz with extensive tensile strength. Our study opens a facile way to design flexible, lightweight and free-standing films as EMI shielding for next-generation flexible electronic devices.

The synthesis, absolute stereochemical configuration, complete biological characterization, mechanism of action and resistance, and pharmacokinetic properties of (S)-(−)-acidomycin are described. Acidomycin possesses promising antitubercular activity against a series of contemporary drug susceptible and drug-resistant M. tuberculosis strains (MICs = 0.096–6.2 μM), but is inactive against non-tuberculosis mycobacteria, gram-positive and gram-negative pathogens (MICs > 1000 μM). Complementation studies with biotin biosynthetic pathway intermediates and subsequent biochemical studies confirmed acidomycin inhibits biotin synthesis with a K(i) of approximately 1 μM through the competitive inhibition of biotin synthase (BioB) and also stimulates unproductive cleavage of S-adenosylmethionine (SAM) to generate the toxic metabolite 5′-deoxyadenosine. Cell studies demonstrate acidomycin selectively accumulates in M. tuberculosis providing a mechanistic basis for the observed antibacterial activity. The development of spontaneous resistance by M. tuberculosis to acidomycin was difficult and only low-level resistance to acidomycin was observed by overexpression of BioB. Collectively, the results provide a foundation to advance acidomycin and highlight BioB as a promising target.

First-principle calculations have been performed to study the sensing of CO gas in various considered configurations. The adsorption of CO on zigzag BN nanoribbon (ZBNNR) and zigzag AlN nanoribbon (ZAlNNR) was modelled in five different possibilities. The effect of CO adsorption is to reduce the band gap in both types (BN/AlN) of the nanoribbons. Interestingly, a finite magnetic moment (0.96 μ B for ZBNNR and 0.69 μ B for ZAlNNR) has been obtained which depends upon the adsorption configuration of CO. Half-metallicity was also observed upon selective CO adsorption on ZAlNNR irrespective of the ribbon width. Present findings suggest that CO gas molecules could be detected through adsorption on BN/AlN nanoribbons via changes in electronic and/or magnetic properties.

Background: Shankhpushpi is an Ayurvedic drug, widely used for its actions on the central nervous system, especially to improve intellect and boost memory. Four botanicals viz. Canscora decussata Schult. (CD), Clitorea ternatea Linn. (CT), Convolvulus pluricaulis Choisy. (CP) and Evolvulus alsinoides Linn. (EA) are considered as sources of Shankhpushpi by Indian practitioners on the basis of their morphological descriptions given in ancient texts. Objective: The present study was undertaken to evaluate the neuropharmacological effect of four herbs commonly identified as source of Shankhpushpi. Materials and methods: Methanol extracts of all four varieties were tested and evaluated in vitro and in vivo for their neuropharmacological effects. Experiments such as protection against β-amyloid induced neurotoxicity on brain cell line (Neuro 2A), antioxidant potential, AchE (acetylcholinesterase enzyme) inhibition, and 5-LOX (lipoxygenase) enzyme inhibition were conducted for in vitro evaluation. For in vivo evaluation, scopolamine (0.3 mg/kg i.p.) induced memory retrieval using pole climbing apparatus and Morris water maze were performed in rat models. Results: It was found that protective effects of EA and CD against β-amyloid induced neurotoxicity in Neuro 2A cells were significantly higher than CT and CP. EA proved to be superior than other varieties on the basis of antioxidant activity, AchE inhibitory and LOX inhibitory activities. The preventive activity of EA on scopolamine induced memory retrieval in pole climbing and Morris water maze task in rats was found to be higher than that of CD, CT and CP. Conclusion: EA has remarkable neuropharmacological effect as compared to other three varieties of Shankhpushpi. This effect may be attributed due to the presence of steroids (stigmasterol and betulinic acid), coumarins (scopoletin) and flavonoids (β-carotene and chlorogenic acid). Hence it can be used as a promising lead in development and management of neuronal disorders including Alzheimer's disease. Keywords: Neuroprotection, Lipoxygenase, Enzyme inhibition, Memory, Shankhpushpi

In this paper polyaniline-Graphene pellets are used for the implementation of a conducting polymer antenna which radiates at 6.8 GHz.The conducting polymer polyaniline is synthesized by oxidative polymerization and rapid mixing process. The conductivity enhancement is done by secondary doping and the incorporation of exfoliated graphene as filler in the polyaniline host matrix. As a result of the filler incorporation, conductivity is enhanced to 5000 S/m and it is pelletized and used as radiating elements of the antenna.FR4 with permittivity 4.4 and loss tangent of 0.001 is used as substrate. The antenna is designed to operate in 6.8GHz and it works with a bandwidth of 450 MHz.The proposed antenna shows a gain of -2.2 dBi for a thickness of 1.92mm.

Aceclofenac (ACE), a cyclooxygenase-2 inhibitor, is the derivative of the diclofenac group that has been in use for the symptomatic treatment of systemic inflammatory autoimmune disease, rheumatoid arthritis (RA). Partial solubility, high lipophilic nature, and stability challenge its use in developing topical formulations. Hence, we developed and characterized nanostructured lipid carrier (NLC)–based ACE (ACE-NLC) hydrogel for an efficient transdermal delivery. NLC microemulsion was prepared using different lipids by various methods and was characterized with respect to particle size, zeta potential, surface morphology, and drug encapsulation efficiency. The optimized NLC formulation was incorporated into Carbopol® 940 gel, and this arrangement was characterized and compared with the existing marketed gel (Mkt-gel) formulation to assess in vitro drug release, rheology, texture profile, in vivo skin retention and permeation, and stability. Furthermore, prepared and characterized ACE-loaded NLC formulation was evaluated for skin integrity and fitted in a dermatokinetic model. The results of this study confirmed the spherical shape; smooth morphology and nanometric size attested by Zetasizer and scanning and transmission electron microcopy; and stability of the ACE-NLC formulation. The ACE-NLC-gel formulation showed good rheological and texture characteristics, and better skin distribution in the epidermis and dermis. Moreover, ACE-NLC permeated deeper in the skin layers and kept the skin integrity intact. Overall, NLC-based gel formulation of ACE might be a promising nanoscale lipid carrier for topical application when compared with the conventional Mkt-gel formulation.

In recent years, erythropoietin (EPO) has emerged as a useful neuroprotective and neurotrophic molecule that produces antidepressant and cognitive-enhancing effects in psychiatric disorders. However, EPO robustly induces erythropoiesis and elevates red blood cell counts. Chronic administration is therefore likely to increase blood viscosity and produce adverse effects in non-anemic populations. Carbamoylated erythropoietin (CEPO), a chemically engineered modification of EPO, is non-erythropoietic but retains the neurotrophic and neurotrophic activity of EPO. Blood profile analysis after EPO and CEPO administration showed that CEPO has no effect on red blood cell or platelet counts. We conducted an unbiased, quantitative, mass spectrometry-based proteomics study to comparatively investigate EPO and CEPO-induced protein profiles in neuronal phenotype PC12 cells. Bioinformatics enrichment analysis of the protein expression profiles revealed the upregulation of protein functions related to memory formation such as synaptic plasticity, long term potentiation (LTP), neurotransmitter transport, synaptic vesicle priming, and dendritic spine development. The regulated proteins, with roles in LTP and synaptic plasticity, include calcium/calmodulin-dependent protein kinase type 1 (Camk1), Synaptosomal-Associated Protein, 25 kDa (SNAP-25), Sectretogranin-1 (Chgb), Cortactin (Cttn), Elongation initiation factor 3a (Eif3a) and 60S acidic ribosomal protein P2 (Rplp2). We examined the expression of a subset of regulated proteins, Cortactin, Grb2 and Pleiotrophin, by immunofluorescence analysis in the rat brain. Grb2 was increased in the dentate gyrus by EPO and CEPO. Cortactin was induced by CEPO in the molecular layer, and pleiotrophin was increased in the vasculature by EPO. The results of our study shed light on potential mechanisms whereby EPO and CEPO produce cognitive-enhancing effects in clinical and preclinical studies.

Rhamnolipids (RLs) are surface-active compounds and belong to the class of glycolipid biosurfactants, mainly produced from Pseudomonas aeruginosa. Due to their non-toxicity, high biodegradability, low surface tension and minimum inhibitory concentration values, they have gained attention in various sectors like food, healthcare, pharmaceutical and petrochemicals. The ecofriendly biological properties of rhamnolipids make them potent materials to be used in therapeutic applications. RLs are also known to induce apoptosis and thus, able to inhibit proliferation of cancer cells. RLs can also act as immunomodulators to regulate the humoral and cellular immune systems. Regarding their antimicrobial property, they lower the surface hydrophobicity, destruct the cytoplasmic membrane and lower the critical micelle concentration to kill the bacterial cells either alone or in combination with nisin possibly due to their role in modulating outer membrane protein. RLs are also involved in the synthesis of nanoparticles for in vivo drug delivery. In relation to economic benefits, the post-harvest decay of food can be decreased by RLs because they prevent the mycelium growth, spore germination of fungi and inhibit the emergence of biofilm formation on food. The present review focuses on the potential uses of RLs in cosmetic, pharmaceutical, food and health-care industries as the potent therapeutic agents.

A wideband non-resonant absorber is proposed, and its radar cross section (RCS) reduction is investigated. A discussion on the functional materials available is followed by the design of an absorber on a Plexiglas substrate with polyaniline-graphene nanocomposite as layered square inclusions with thicknesses and conductivities scaled to golden ratio. The measured dielectric properties of polyaniline-graphene nanocomposites are used in the fullwave simulation. The design parameters have been identified and optimized using CST Microwave Studio. As designed structure is fabricated and the reflection is measured. The objective of the work is to demonstrate the use of non-metallic conducting polymer composites devoid of metals for radar absorbing material (RAM) structural designs. The structure is an all-polymer and electrically thin design with a potential to be 3D printed to suit the target object.

Cancer cells hijack autophagy pathway to evade anti-cancer therapeutics. Many molecular signaling pathways associated with drug-resistance converge on autophagy induction. Honokiol (HNK), a natural phenolic compound purified from Magnolia grandiflora, has recently been shown to impede breast tumorigenesis and, in the present study, we investigated whether breast cancer cells evoke autophagy to modulate therapeutic efficacy and functional networks of HNK. Indeed, breast cancer cells exhibit increased autophagosomes-accumulation, MAP1LC3B-II/LC3B-II-conversion, expression of ATG proteins as well as elevated fusion of autophagosomes and lysosomes upon HNK treatment. Breast cancer cells treated with HNK demonstrate significant growth inhibition and apoptotic induction, and these biological processes are blunted by macroautophagy/autophagy. Consequently, inhibiting autophagosome formation, abrogating autophagosome-lysosome fusion or genetic-knockout of BECN1 and ATG7 effectively increase HNK-mediated apoptotic induction and growth inhibition. Next, we explored the functional impact of tumor suppressor STK11 in autophagy induction in HNK-treated cells. STK11-silencing abrogates LC3B-II-conversion, and blocks autophagosome/lysosome fusion and lysosomal activity as illustrated by LC3B-Rab7 co-staining and DQ-BSA assay. Our results exemplify the cytoprotective nature of autophagy invoked in HNK-treated breast cancer cells and put forth the notion that a combined strategy of autophagy inhibition with HNK would be more effective. Indeed, HNK and chloroquine (CQ) show synergistic inhibition of breast cancer cells and HNK-CQ combination treatment effectively inhibits breast tumorigenesis and metastatic progression. Tumor-dissociated cells from HNK-CQ treated tumors exhibit abrogated invasion and migration potential. Together, these results implicate that breast cancer cells undergo cytoprotective autophagy to circumvent HNK and a combined treatment with HNK and CQ can be a promising therapeutic strategy for breast cancer.

Peroxiredoxins (Prxs) are antioxidant proteins that are involved in cellular defence against reactive oxygen species and reactive nitrogen species. Humans have six peroxiredoxins, hPrxI-VI, out of which hPrxI and hPrxII belongs to the typical 2-Cys class sharing 90% conservation in their amino acid sequence including catalytic residues required to carry out their peroxidase and chaperone activities. Despite the high conservation between hPrxI and hPrxII, hPrxI behaves differently from hPrxII in its peroxidase and chaperone activity. We recently showed in yeast that in the absence of Tsa1 and Tsa2 (orthologs of hPrx) hPrxI protects the cells against different stressors whereas hPrxII does not. To understand this difference, we expressed catalytic mutants of hPrxI in yeast cells lacking the orthologs of hPrxI/II. We found that the catalytic mutants lacking peroxidase function including hPrxIC52S, hPrxIC173S, hPrxIT49A, hPrxIP45A and hPrxIR128A were not able to grow on media with nitrosative stressor (sodium nitroprusside) and unable to withstand heat stress, but surprisingly they were able to grow on an oxidative stressor (H2O2). Interestingly, we found that hPrxI increases the expression of antioxidant genes, GPX1 and SOD1, and this is also seen in the case of a catalytic mutant, indicating hPrxI can indirectly reduce oxidative stress independently of its own peroxidase function and thus suggesting a novel role of hPrxI in altering the expression of other antioxidant genes. Furthermore, hPrxIC83T was resistant to hyperoxidation and formation of stable high molecular weight oligomers, which is suggestive of impaired chaperone activity. Our results suggest that the catalytic residues of hPrxI are essential to counter the nitrosative stress whereas Cys83 in hPrxI plays a critical role in hyperoxidation of hPrxI., Graphical abstract Image 1

First-principle investigations under the flagship of density functional theory have been performed to analyze the prospects of antimonene nanoribbons (SbNR) for carbon mono-oxide (CO) and nitric oxide (NO) sensing applications. We have explored various adsorption configurations of gas molecules on the edges of bare and silicon-doped SbNR with zigzag and armchair edge states. Based on adsorption energy ( $$E_{\text{ads}}$$ ) calculations, it is revealed that CO and NO molecules tend to physisorbed on SbNRs substrate. However, upon the introduction of silicon impurity, gas molecules prefer to chemisorb on SbNRs. The electronic properties’ calculations based on band structures and density of states (DOS) profile predict substantial modification in the band structures of the SbNRs after CO and NO adsorption. Charge transfer analysis indicates that gas molecules act as an acceptor on undoped SbNRs whereas act as a donor on a substitutionally doped substrate. To explore deep into the interaction between the gas molecule and SbNRs’ substrate, charge difference density and projected DOS have been plotted and examined. Furthermore, to determine the feasibility, I–V characteristics have been calculated using a standard two-probe model. It is evident from I–V characteristics that gas adsorption has a prominent impact on the current-carrying capability of SbNR. Finally, the recovery time is calculated to analyze the desorption performance of CO/NO adsorbed on bare and Si-doped SbNRs, henceforth projecting the potential of SbNRs for CO and NO sensor applications.

The present study was designed to develop pH-sensitive lipid polymer hybrid nanoparticles (pHS-LPHNPs) for specific cytosolic-delivery of docetaxel (DTX). The pHS-LPHNPs-DTX formulation was prepared by self-assembled nano-precipitation technique and characterized for zeta potential, particle size, entrapment efficiency, polydispersity index (PDI), and in vitro drug release. In vitro cytotoxicity of pHS-LPHNPs-DTX was assessed on breast cancer cells (MDA-MB-231 and MCF-7) and compared with DTX-loaded conventional LPHNPs and bare DTX. In vitro cellular uptake in MDA-MB-231 cell lines showed better uptake of pHS-LPHNPs. Further, a significant reduction in the IC50 of pHS-LPHNPs-DTX against both breast cancer cells was observed. Flow cytometry results showed greater apoptosis in case of pHS-LPHNPs-DTX treated MDA-MB-231 cells. Breast cancer was experimentally induced in BALB/c female mice, and the in vivo efficacy of the developed pHS-LPHNPs formulation was assessed with respect to the pharmacokinetics, biodistribution in the vital organs (liver, kidney, heart, lungs, and spleen), percentage tumor burden, and survival of breast cancer-bearing animals. In vivo studies showed improved pharmacokinetic and target-specificity with minimum DTX circulation in the deep-seated organs in the case of pHS-LPHNPs-DTX compared to the LPHNPs-DTX and free DTX. Mice treated with pHS-LPHNPs-DTX exhibited a significantly lesser tumor burden than other treatment groups. Also, reduced distribution of DTX in the serum was evident for pHS-LPHNPs-DTX treated mice compared to the LPHNPs-DTX and free DTX. In essence, pHS-LPHNPs mediated delivery of DTX presents a viable platform for developing therapeutic-interventions against breast-cancer.

Although the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/ CRISPR associated protein 9 (Cas9) technique has dramatically lowered the cost and increased the speed of generating genetically engineered mice, success depends on using guide RNAs and donor DNAs which direct efficient knock-out (KO) or knock-in (KI). By Sanger sequencing DNA from blastocysts previously injected with the same CRISPR components intended to produce the engineered mice, one can test the effectiveness of different guide RNAs and donor DNAs. We describe in detail here a simple, rapid (three days), inexpensive protocol, for amplifying DNA from blastocysts to determine the results of CRISPR point mutation KIs. Using it, we show that (1) the rate of KI seen in blastocysts is similar to that seen in mice for a given guide RNA/donor DNA pair, (2) a donor complementary to the variable portion of a guide integrated in a more all-or-none fashion, (3) donor DNAs can be used simultaneously to integrate two different mutations into the same locus, and (4) by placing silent mutations about every 6 to 10 bp between the Cas9 cut site and the desired mutation(s), the desired mutation(s) can be incorporated into genomic DNA over 30 bp away from the cut at the same high efficiency as close to the cut.

Summary Introduction: Shankhpushpi has been widely used in traditional Indian systems of medicine as a brain and memory boosting tonic. There are a variety of botanicals reported to be used as sources of Shankhpushpi in various parts of India. For instance, Canscora decussata Schult, Clitorea ternatea Linn., Convolvulus pluricaulis Choisy. and Evolvulus alsinoides Linn. are most commonly used as sources of Shankhpushpi by practitioners of Ayurveda in different parts of the country. Objective: When it comes to using Shankhpushpi in herbal formulations, qualitative and quantitative analysis of the correct botanicals in the formulation decides its pharmacological effectiveness. Scopoletin and mangiferin are proven bioactive markers identified in Shankhpushpi botanicals in our previous studies. Hence the study is aimed at providing a simple analytical method for the identification of the correct variety of Shankhpushpi using proven markers. Methods: In this study, a High Performance Liquid Chromatographic (HPLC) method has been developed for the estimation of scopoletin and mangiferin levels in four botanicals of Shankhpushpi and their marketed formulations. Result: A simple analytical method was developed which proved to be very crucial in estimating concentrations of mangiferin and scopoletin in various test samples. This method can be used to identify the correct botanicals of Shankhpushpi present in any Ayurvedic formulation or raw material or processed powder by evaluating the content of scopoletin or mangiferin as markers. Conclusion: The developed HPLC method is a quick and reliable method for the quantitative monitoring of mangiferin and scopoletin in herbal extracts and marketed formulations of Shankhpushpi.

This work investigates the impact of cove edges in gallium nitride nanoribbons (GaNNRs) as cove edges nanoribbons are energetically more stable and facilitates further tunability of electronic properties of nanoribbons. Here structural, electronic, and transport properties of cove edged GaNNRs with hydrogen (H) passivation are investigated. For this investigation, the framework of non-equilibrium Green function (NEGF) formalism based on density functional theory (DFT) has been deployed. The effect of cove edge at nitrogen (N), gallium (Ga), and at both the edges for its potential ultra-scaled device applications are studied. As compared to the pristine semiconducting nature of H–GaN–H, present DFT-based calculations of cove edged GaNNRs exhibit a metallic nature via selective H-passivation. A comparative study of binding energy (E b ) revealed that the C–GaN–H nanoribbon is structurally more stable irrespective of the width in all considered cove edged GaNNRs. Interestingly, the proposed two-terminal cove edged GaNNRs devices exhibit negative differential resistance (NDR) effect based on selective edge passivation with hydrogen atoms. The observed NDR behavior suggests that cove edged GaNNRs with selective H-passivated GaNNRs have immense potential applications for preparing nanoscale NDR devices.

This work investigates the structural stability, electronic and transport properties of zigzag boron nitride nanoribbons (ZBNNRs) with hydrogenation/fluorination by using density functional theory (DFT) along with non-equilibrium Green’s function (NEGF) approach. The study reveals that ZBNNRs exhibit metallic to semiconducting transition via selected edge fluorination. Interestingly, edge fluorinated ZBNNRs demonstrate high structural stability due to the higher electronegativity of fluorine. It is also revealed that negative differential resistance (NDR) has also been observed for edge fluorinated two terminal devices with enormously high peak to valley current ratio (PVCR) of the order of 1 0 11 . We have also investigated the gate controllable current–voltage (I–V) characteristics of three terminal ZBNNRs field effect transistor (FET). The selective structures exhibit excellent gate controllability which can tune the observed PVCR. Our findings indicate the potential of fluorinated ZBNNRs towards upcoming ultra fast switches, rectifiers and oscillators etc.

Withaferin A (WFA), a steroidal lactone, negatively regulates breast cancer growth however, its mechanisms of action remain largely elusive. We found that WFA blocks autophagy flux and lysosomal proteolytic activity in breast cancer cells. WFA increases accumulation of autophagosomes, LC3B-II-conversion, expression of autophagy-related proteins and autophagosome/lysosome fusion. Autolysosomes display the characteristics of acidic compartments in WFA-treated cells; however, the protein degradation activity of lysosomes is inhibited. Blockade of autophagic flux reduces the recycling of cellular fuels leading to insufficient substrates for tricarboxylic acid (TCA) cycle and impaired oxidative phosphorylation. WFA decreases expression and phosphorylation of LDHA, the key enzyme that catalyzes pyruvate-to-lactate conversion, reduces ATP levels and increases AMPK activation. AMPK-inhibition abrogates while AMPK-activation potentiates WFA's effect. WFA and 2-deoxyglucose combination elicits synergistic inhibition of breast cancer cells. Genetic-knockout of BECN1 and ATG7 fails to rescue cells from WFA-treatment; in contrast, addition of methyl pyruvate to supplement TCA cycle protects WFA-treated cells. Together, these results implicate that WFA is a potent lysosomal inhibitor; energetic impairment is required for WFA-induced apoptosis and growth-inhibition and combining WFA and 2DG is a promising therapeutic strategy for breast cancer.

Ion bombardment on graphene sheets can produce atomic vacancies that can trap metal atoms. In this paper, we demonstrated that these trapped metal atoms can effectively bind other molecules with heteroatoms, making them chemisorbed to the graphene. The trapped cobalt atom can bind sarin molecule through fluorine atom with dissociation energy significantly higher than the one bonded via oxygen atom. This suggests that it can displace water molecule and therefore pledge for sarin chemisorbent in atmospheric environment. Our investigations also revealed that metallic character is enhanced upon sarin adsorption unlike the bonding of water molecule with trapped metal atom in graphene lattice which causes an opening of small (0.02 eV) band gap. Present findings can have promising application towards detecting the presence of toxic sarin molecules.

Emergence of the multidrug resistant human pathogenic strains is posing a serious health challenge. Resistant strains carry mutations which help them to resist conventional drugs. Therefore, it is required to produce more effective agents that are able to degrade the resistant pathogenic bacterial strains. The antimicrobial properties of nanoparticles (NPs) by eco-friendly green synthetic methods have pulled attention everywhere owing to their exceptional properties and small particle size of 100 nm. NPs are considered to belong to a group of antimicrobial agents which have ability to go inside microbial cells and kill them. In this comprehensive review, we are discussing the green synthetic methods used for the synthesis of NPs targeting the microbes. Additionally, several characterization techniques of antimicrobial NPs are also discussed. Subsequently, various methods used for the analysis of antimicrobial activities and their mechanisms are also examined.

Xanthones are important chemical class of bioactive products that confers therapeutic benefits. Of several xanthones, mangiferin is known to be distributed widely across several fruits, vegetables and medicinal plants. Mangiferin has been shown to exert neuroprotective effects in both in-vitro and in-vivo models. Mangiferin attenuates cerebral infarction, cerebral edema, lipid peroxidation (MDA), neuronal damage, etc. Mangiferin further potentiate levels of endogenous antioxidants to confer protection against the oxidative stress inside the neurons. Mangiferin is involved in the regulation of various signaling pathways that influences the production and levels of proinflammatory cytokines in brain. Mangiferin cosunteracted the neurotoxic effect of amyloid-beta, MPTP, rotenone, 6-OHDA etc and confer protection to neurons. These evidence suggested that the mangiferin may be a potential therapeutic strategy for the treatment of various neurological disorders. The present review demonstrated the pharmacodynamics-pharmacokinetics of mangiferin and neurotherapeutic potential in several neurological disorders with underlying mechanisms.

We have investigated the electronic and structural properties of pristine Zinc-blende type InP nanowires (NWs) by using ab-initio approach. We have considered the effect of phases by taking NWs of 7 A radii in three phases viz. (100), (110), (111). It is revealed that the electronic properties of NWs are highly affected by the wire phases. NW in (100) phase is found to be semiconducting with an indirect band gap of 0.71 eV whereas it becomes semi-metallic and metallic in other two phases. Thus, the nature of nanowires is observed as a function of NW phases. Further, energetic feasibility of InP NWs strongly dependent on their growth phase. Copyright © 2016 VBRI Press.

The present study was designed to engineer surface-anchored and methotrexate loaded lipobrid nano-constructs for targeting breast cancer. Ligands (fucose, galactose and mannose) anchored lipobrid nano-constructs were used to compare and assess delivery efficiency in breast cancer cell lines as well as in DMBA induced breast cancer animal model. The developed and characterized formulations were used to comparatively assess cellular uptake, cell-viability, apoptosis, lysosomal membrane permeability, bioavailability, bio-distribution, changes in tumor volume and animal survival. Our results show greater cellular uptake, cytotoxicity at low IC50, apoptosis with altered lysosomal membrane permeability and greater rate of degradation of lysosomal membrane. We saw better bioavailability and tumor targeting efficiency with minimum secondary organ drug distribution. The significant reduction was seen in tumor burden with ligand anchored lipobrids in comparison to plain and MTX-lipobrid formulations. In conclusion, fucose anchored MTX-lipobrid formulation showed promising results, and warrants to explore the development of therapeutic interventions for breast cancer.

Receptor-like cytoplasmic kinases (RLCKs) inArabidopsisplay a central role in the integration of signaling input from various growth and immune signaling pathways. BOTRYTIS-INDUCED KINASE 1 (BIK1), belonging to the RLCK family, is an important player in defense against bacterial and fungal pathogens and in ethylene and brassinosteroid hormone signaling. In this study, the purification and crystallization of a first member of the class VI family of RLCK proteins, BIK1, are reported. BIK1 was crystallized using the microbatch-under-oil method. X-ray diffraction data were collected to 2.35 Å resolution. The crystals belonged to the monoclinic space groupC2, with two monomers per asymmetric unit.

Labeling of proteins with fluorinated amino acids and using fluorine-19 NMR greatly simplifies the NMR spectrum. Changes in the spectrum on interaction with ligands makes protein-observed fragment-based drug screening possible. NMR spectroscopy can be used to quantify the binding affinity between proteins and low-complexity molecules, termed 'fragments'; this versatile screening approach allows researchers to assess the druggability of new protein targets. Protein-observed 19F-NMR (PrOF NMR) using 19F-labeled amino acids generates relatively simple spectra that are able to provide dynamic structural information toward understanding protein folding and function. Changes in these spectra upon the addition of fragment molecules can be observed and quantified. This protocol describes the sequence-selective labeling of three proteins (the first bromodomains of Brd4 and BrdT, and the KIX domain of the CREB-binding protein) using commercially available fluorinated aromatic amino acids and fluorinated precursors as example applications of the method developed by our research group. Fragment-screening approaches are discussed, as well as Kd determination, ligand-efficiency calculations and druggability assessment, i.e., the ability to target these proteins using small-molecule ligands. Experiment times on the order of a few minutes and the simplicity of the NMR spectra obtained make this approach well-suited to the investigation of small- to medium-sized proteins, as well as the screening of multiple proteins in the same experiment.

In this paper, we have investigated a novel nanogap embedded dielectric modulated schottky tunneling source impact-ionization MOS (DM-STS-IMOS) for highly sensitive, real-time label-free electrical detection of bio-molecules. The current gating mechanism of STS-IMOS is governed by cumulative effect of both impact ionization and source induced tunneling. Both of these mechanisms are synergistically leveraged for pathogenic biomolecule sensors design scheme. Technology computer-aided design (TCAD) simulation study is deployed to provide physical insight into the working mechanism and performance estimation of the proposed sensor. DM-STS-IMOS exhibits enhanced sensitivity and as the operating voltage of DM-STS-IMOS is lower than the conventional IMOS, it has significantly enhanced reliability and higher power efficiency. The length of the nanogap is recognized as a potential parameter to optimize the device sensitivity. It demonstrates dominant dielectric modulation effects, easy recovery mechanism and higher sensitivity even at smaller channel lengths. It can also be exploited in array-based screening and in-vivo bio-species diagnostics. Fig. The proposed dielectric modulated schottky tunneling source impact-ionization MOS (DM-STS-IMOS).A novel nanogap embedded dielectric modulated schottky tunneling source impact-ionization MOS (DM-STS-IMOS) for highly sensitive, label-free electrical detection of bio-molecules.Display Omitted Investigated a novel dielectric modulated schottky tunneling source IMOS bio-sensorIt offers highly sensitive, label-free electrical detection of bio-molecules.Sensitivity can be optimized by varying the length of nanogap.TCAD study is deployed to provide physical insight of working mechanism of our device.

The antibacterial properties of twenty-eight novel ricinoleic acid glycosides synthesized by Koenigs–Knorr glycosylation are reported. Seven of them were found to show promising wide spectrum antibacterial activity against Gram positive bacteria of which two compounds, the mannopyranosyl- and the arabinofuranosyl derivatives, were proven effective against various non-clinical/clinical/NorA-overexpressed/resistant strains of Staphylococcus aureus as well as other Gram +ve bacteria such as Bacillus subtilis ATCC 6051 and Micrococcus luteus MTCC 2470. It was found that both the presence of the sugar and its structure are necessary and important for the compounds to be bioactive. The methyl ester protection of the carboxylic acid moiety of the ricinoleic acid unit was also found to be important for imparting good bioactivity to the molecule. Based on the membrane permeability and cell disintegration studies, these compounds are found to increase the bacterial cell membrane permeability, subsequently causing cell death.

We predict the possibility of spin based electronic transport in edge fluorinated armchair boron nitride nanoribbons (ABNNRs). The structural stability, electronic and magnetic properties of these edge fluorinated ABNNRs have been systematically analyzed by means of first-principles calculations within the local spin-density approximation (LSDA). Regardless of their width, ABNNRs with F-passivation at only the edge-B atoms are found to be thermodynamically stable and half-metallic in nature. The spin polarized states are found to be ∼0.4 eV more stable than that of spin compensated states. Further, upto 100% spin polarization is expected in ABNNRs with F-passivation at only the edge-B atoms as indicated by the giant splitting of spin states which is observed in the corresponding band structures, DOS and transmission spectrum. The existence of half-metallicity is attributed to the localization of electronic charge at unpassivated edge-N atoms as revealed from the analysis of Bloch states and projected density of states (PDOS). Importantly, present stability analysis suggests that the possibility of experimental realization of spin polarized transport in ABNNRs is more promising via F-passivation of ribbon edges than that of H-passivation. The observed half-metallic nature and large difference in the energies (∼0.4 eV) of spin polarized and spin compensated states projects these half-metallic ABNNRs as potential candidates for inorganic spintronic applications.

Despite the adverse effects of microbial hazards on public health, major pharmaceutical firms have left the field of anti-infective development and a dramatic reduction in the number of researcher's intricated in the quest for new specific anti-infective leads. In the non-existence of an efficient forum for antibiotics development and over usage in human beings and animals, bacteria have demoralized this potential by gradually establishing the resistance toward most of the antibiotics used. Thus, the production of novel and successful anti-infective drugs is urgently required to combat this resistance. Hydrazones and hydrazides have mounted as a key-skeleton for the development of active drugs, due to their important biological and pharmacological profiles. Hydrazones are being manufactured as medicines by various investigators to fight against the ailments with maximal effects and minimal toxicity. This paper focuses on the outline of the literature results of recent years, incorporating the work on the anti-infective profile of hydrazone analogues. This review may also act as an excellent basis for the development of new derivatives of hydrazone as potential anti-infective mediators.