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Seeman's pioneer idea has led to the foundation of DNA nanostructures, resulting in a remarkable advancement in DNA nanotechnology. Over the last few decades, remarkable advances in drug delivery techniques have resulted in the self-assembly of DNA for encapsulating candidate drug molecules. The nuclear targeting capability of DNA nanostructures is lies within their high spatial addressability and tremendous potential for active targeting. However, effective programming and assembling those DNA molecules remains a challenge, making the path to DNA nanostructures for real-world applications difficult. Because of their small size, most nanostructures are self-capable of infiltrating into the tumor cellular environment. Furthermore, to enable controlled and site-specific delivery of encapsulated drug molecules, DNA nanostructures are functionalized with special moieties that allow them to bind specific targets and release cargo only at targeted sites rather than non-specific sites, resulting in the prevention/limitation of cellular toxicity. In light of this, the current review seeks to shed light on the versatility of the DNA molecule as a targeting and encapsulating moiety for active drugs in order to achieve controlled and specific drug release with spatial and temporal precision. Furthermore, this review focused on the challenges associated with the construction of DNA nanostructures as well as the most recent advances in the functionalization of DNA nanostructures using various materials for controlled and targeted delivery of medications for cancer therapy. [ABSTRACT FROM AUTHOR]

Seeman's pioneer idea has led to the foundation of DNA nanostructures, resulting in a remarkable advancement in DNA nanotechnology. Over the last few decades, remarkable advances in drug delivery techniques have resulted in the self-assembly of DNA for encapsulating candidate drug molecules. The nuclear targeting capability of DNA nanostructures is lies within their high spatial addressability and tremendous potential for active targeting. However, effective programming and assembling those DNA molecules remains a challenge, making the path to DNA nanostructures for real-world applications difficult. Because of their small size, most nanostructures are self-capable of infiltrating into the tumor cellular environment. Furthermore, to enable controlled and site-specific delivery of encapsulated drug molecules, DNA nanostructures are functionalized with special moieties that allow them to bind specific targets and release cargo only at targeted sites rather than non-specific sites, resulting in the prevention/limitation of cellular toxicity. In light of this, the current review seeks to shed light on the versatility of the DNA molecule as a targeting and encapsulating moiety for active drugs in order to achieve controlled and specific drug release with spatial and temporal precision. Furthermore, this review focused on the challenges associated with the construction of DNA nanostructures as well as the most recent advances in the functionalization of DNA nanostructures using various materials for controlled and targeted delivery of medications for cancer therapy. [ABSTRACT FROM AUTHOR]

Glaucoma is a leading cause of irreversible blindness worldwide. Reducing intraocular pressure is currently the only effective treatment. Elevated intraocular pressure is associated with increased resistance of the outflow pathway, mainly the trabecular meshwork (TM). Despite great progress in the field, the development of novel and effective treatment for glaucoma is still challenging. In this study, we reported that human induced pluripotent stem cells (iPSCs) can be cultured as colonies and monolayer cells expressing OCT4, alkaline phosphatase, SSEA4 and SSEA1. After induction to neural crest cells (NCCs) positive to NGFR and HNK1, the iPSCs can differentiate into TM cells. The induced iPSC-TM cells expressed TM cell marker CHI3L1, were responsive to dexamethasone treatment with increased expression of myocilin, ANGPTL7, and formed CLANs, comparable to primary TM cells. To the best of our knowledge, this is the first study that induces iPSCs to TM cells through a middle neural crest stage, which ensures a stable NCC pool and ensures the high output of the same TM cells. This system can be used to develop personalized treatments using patient-derived iPSCs, explore high throughput screening of new drugs focusing on TM response for controlling intraocular pressure, and investigate stem cell-based therapy for TM regeneration. Image 1 • A novel two-step induction approach from iPSCs to neural crest then to TM cells. • Neural crest cells can be stored that ensures same lot and large number of TM cells. • Differentiated TM cells expressed TM markers and lost iPSC and neural crest markers. • Differentiated TM cells responded to dexamethasone with increased glaucoma genes. • A model for cell transplantation, drug discovery and disease modelling in glaucoma. [ABSTRACT FROM AUTHOR]

Curcumin, derived from turmeric, has a strong anticancer potential known for millennia. The development of this phytochemical as a medicine has been hampered by several significant deficiencies, including its poor water solubility and low bioavailability. This review article discusses possibilities to overcome these bottlenecks by focusing on this natural polyphenol's nanoformulation. Moreover, preparation of curcumin conjugates containing folates as ligands for folic acid receptors can add a new important dimension in this field, allowing specific targeting of cancer cells, considering the significantly higher expression of these receptors in malignant tissues compared to normal cells. It is highly expected that simultaneous improvement of different aspects of curcumin in fighting against such a complex and multifaceted disease like cancer. Therefore, we can better comprehend cancer biology by developing a mechanistic understanding of curcumin, which will also inspire the scientific community to develop new pharmacological models, and exploration of emerging directions to revitalize application of natural products in cancer therapy. [Display omitted] • Numerous malignant tumours have been reported to have highly expressed folate receptors. • Use of curcumin-incorporated nano-formulations to target malignant cells with high specificity using folate receptors. • Role of folate receptors in early diagnosis of cancer. • Safety aspects of curcumin nano-formulations [ABSTRACT FROM AUTHOR]

Abstract We investigate whether the λ -tensor product of operator spaces which includes the operator space projective, Haagerup and Schur tensor products, and the λ -tensor product of operator systems commute with inductive limits, in the sense that if (X n , ϕ n) is an inductive system of operator spaces (or operator systems) with an inductive limit X , and if Y is any operator space (or operator system), then whether (X n ⨂ λ Y , ϕ n ⊗ id) becomes an inductive system, and if so, whether the inductive limit of this system is same as X ⨂ λ Y , where ⨂ λ denotes the λ -tensor product of operator spaces (or operator systems). We also discuss about the bidual of such an inductive limit and obtain embeddings lim → (X n ⁎ ⁎ ⨂ λ Y ⁎ ⁎) ⊆ (lim → X n ⨂ λ Y) ⁎ ⁎ under certain restrictions. [ABSTRACT FROM AUTHOR]

Abstract In this paper, RF noise modeling of Black Phosphorus Junctionless Trench (BP-JL-T) MOSFET has been investigated in strong inversion region. The simulated and modeled results are simultaneously compared with Conventional Trench (CT) MOSFET at THz frequency range. By using analytical expressions from RF equivalent schematic, few RF figure-of-merits (FOMs) have been evaluated. It is found that RF noise parameters such as noise resistance (R n), minimum noise figure (NF min), optimum source susceptance (B opt) and conductance (G opt) are reduced to more than 200%. Modeled results reveal that BP-JL-T-MOSFET minimizes RF noise thus, providing the detailed insight to RF engineers for microwave applications/RFIC design. Highlights • RF noise modeling of BP-JL-T-MOSFET has been investigated in strong inversion region. • By using analytical expressions from RF equivalent schematic, RF FOMs have been evaluated. • RF noise parameters such as R n , NF min , B opt and G opt are reduced more that 200%. • Modeled results reveal that BP-JL-T-MOSFET minimizes RF noise. • It providing the detailed insight to RF engineers for microwave applications/RFIC design. [ABSTRACT FROM AUTHOR]

In this work, a comprehensive analog and RF performance of a novel Black Phosphorus-Junctionless-Recessed Channel (BP-JL-RC) MOSFET has been explored at 45 nm technology node (Gate length = 20 nm). The integration of black phosphorus with junctionless recessed channel MOSFET, leads to higher drain current of about 0.3 mA and excellent switching ratio (of the order of 10 11 ) due to reduced off-current which leads to improvement in sub-threshold slope (SS) (67mV/dec). Further, RF performance metrics have also been studied with an aim to analyze high-frequency performance. The following FOMs have been evaluated: cut-off frequency ( f T ), maximum oscillator frequency ( f MAX ), stern stability factor, various power gains and parasitic capacitances at THz frequency range. Thus, in addition to the high packing density offered by RC MOSFET, the proposed design finds numerous application at THz frequency making it a promising candidate at wafer scale integration level. [ABSTRACT FROM AUTHOR]

This paper discusses the impact of trench depth (Negative Junction Depth (NJD)) and gate length (L G ) shrinking on analog and linearity performance of Transparent Gate Recessed Channel (TGRC) MOSFET with an aim to achieve a reliable and high performance transistor. It is found that device enhances the I ON by 38% and thereby improves the analog performance in terms of transconductance, device efficiency, output resistance, and gain. Moreover, linearity figure of merits are also enhanced at lower gate bias in TGRC MOSFET in comparison to conventional and Conventional Recessed Channel (CRC) MOSFET due to reduced harmonic distortions (g m3 ). Thus, the improved analog and linearity performance at 5 nm NJD and 20 nm L G of TGRC-MOSFET makes it suitable for low power linear RF amplifiers as a nano-scaled device. Thus, these results would serve as a worthy design tool for low power and high performance CMOS circuits. [ABSTRACT FROM AUTHOR]

Infections due to Acinetobacter baumannii (A. baumannii) are rapidly increasing worldwide and consequently therapeutic options for treatment are limited. The emergence of multi drug resistant (MDR) strains has rendered available antibiotics ineffective, necessitating the urgent discovery of new drugs and drug targets. The vitamin B6 biosynthetic pathway has been considered as a potential antibacterial drug target but it is as yet uncharacterized for A. baumannii. In the current work, we have carried out in silico and biochemical characterization of Erythrose-4-phosphate dehydrogenase (E4PDH) (EC 1.2.1.72). This enzyme catalyzes the first step in the deoxyxylulose-5-phosphate (DXP) dependent Vitamin B6 biosynthetic pathway i.e. the conversion of d -erythrose-4-phosphate (E4P) to 4-Phosphoerythronate. E4PDH also possesses an additional activity whereby it can catalyze the conversion of Glyceraldehyde-3-phosphate (G3P) to 1,3 bisphosphoglycerate (1,3BPG). Our studies have revealed that this enzyme exhibits an alternate moonlighting function as a cell surface receptor for the human iron transport proteins transferrin (Tf) and lactoferrin (Lf). The present work reports the internalization of Tf and consequent iron acquisition as an alternate strategy for iron acquisition. Given its essential role in two crucial pathways i.e. metabolism and iron acquisition, A. baumannii E4PDH may play a vital role in bacterial pathogenesis. • The study identifies the presence of the DXP-dependent pathway Vitamin B6 synthesis in A.baumannii. • Cloning and characterization of E4PDH was carried out using biochemical and in silico methods. • E4PDH demonstrated dual substrate specificity, alongwith variable sensitivity to inhibitors H202 and Ethyl bromo pyruvate (EBP). • Significant differences were observed in the catalytic activity of the enzyme as compared to the E.coli homolog-. • E4PDH was found was identified as a cell surface receptor for human iron transport proteins-Transferrin and Lactoferrin revealing the biochemical and moonlighting function of E4PDH. [ABSTRACT FROM AUTHOR]

Understanding the physics of charge carrier transport at graphene/p-GaN interface is critical for achieving efficient device functionality. Currently, the graphene/p-GaN interface is being explored as light emitting diodes, however this interface can be probed as a potential photovoltaic cell. We report the intimate interfacing of mechanically exfoliated graphene (EG), conducting polymer (PEDOT:PSS) and composite of reduced graphene oxide (rGO) and PEDOT:PSS with a wide band gap p-GaN layer. To explore their potential in energy harvesting, three heterojunction devices such as: (i) EG/p-GaN/sapphire, (ii) PEDOT:PSS/p-GaN/sapphire and (iii) PEDOT:PSS(rGO)/p-GaN/sapphire are designed and their photovoltaic characteristics are examined. It is interesting to observe that the EG/p-GaN/sapphire solar cell exhibits high open-circuit voltage of 0.545 V with low ideality factor and reverse saturation current. However, improved short circuit current density (13.7 mA/cm 2 ) is noticed for PEDOT:PSS/p-GaN/sapphire solar cell because of enhanced conductivity accompanied by high transmittance for PEDOT:PSS. Further, the low series resistance for PEDOT:PSS(rGO)/p-GaN/sapphire is observed suggesting that the PEDOT:PSS and rGO composite is well dispersed and exhibits low interfacial resistances with p-GaN. The present investigation leverages the potential of graphene, conducting polymer and their composites as dual capability of (a) transparent and current spreading electrode and (b) an active top layer to make an intimate contact with wide bandgap p-type GaN for possible prospect towards high performance diodes, switches and solar cells. [ABSTRACT FROM AUTHOR]

In this work, power gain assessment and intrinsic delay of Transparent Gate Recessed Channel (TGRC) MOSFET have been observed for RF applications and the results so obtained have been compared with Conventional Recessed Channel (CRC) MOSFET. Simulation results show that TGRC architecture has significantly improved the power gains in terms of maximum available power gain (Gma), maximum transducer power gain (G MT ), maximum stable power gain (Gms) and appreciable reduction in intrinsic delay as compared to CRC-MOSFET owing to indium tin oxide (ITO) in recessed channel as a conducting gate material and thus providing its efficacy for low power switching applications. Further, effect of gate length scaling has also been observed on TGRC MOSFET and it has been found that the cut-off frequency ( f T ) and maximum oscillator frequency ( f MAX ) enhances by 66% and 36% respectively as channel length scales down to 20 nm. Further, the effect of negative junction depth, oxide thickness and substrate doping have also been investigated for TGRC-MOSFET. This TCAD assessment has been done at frequencies of several THz which fortify its use for high frequency RF/wireless applications. [ABSTRACT FROM AUTHOR]

Lysophosphatidic acid (LPA) is a lipid mediator that modulates a wide variety of cellular functions. Elevated LPA signaling has been reported in patients with colorectal cancer or inflammatory bowel diseases, and the tumorigenic role of LPA has been demonstrated in experimental models of colon cancer. However, emerging evidence indicates the importance of LPA signaling in epithelial wound healing and regulation of intestinal electrolyte transport. Here, we briefly review current knowledge of the biological roles of LPA signaling in the intestinal tract. [ABSTRACT FROM AUTHOR]

Forward osmosis (FO) is the futuristic membrane desalination technology as it transcends the disadvantages of other pressure-driven techniques. But, there still remain critical challenges like fabrication of highly permeable membrane with ideal structures maintaining high rejection rates that need to be addressed for implementation as a practical technology. In this work, novel thin-film composite (TFC) membranes were fabricated by means of incorporating manganese oxide (MnO 2) incited graphene quantum dots (GQDs) nanocomposite into a cellulose acetate (CA) suspension followed by phase inversion (PI) for enhanced FO performance. The surface morphology and chemical structure of fabricated membranes were studied using various characterization techniques like XRD, FT-IR, SEM-EDS, Mapping, AFM, and TGA. The structural parameters, water flux, reverse salt flux and salt rejection was estimated on the basis of data obtained from four varying initial draw solution concentrations. At high nanocomposites stacking, the hydrophilicity of the casting blend increase, and subsequently, the PI exchange rate additionally increases, which brings about noticeable difference in the surface morphology. The membrane with 0.5 wt% nanocomposite exhibited superior FO separation performance with osmotic water flux of 18.89, 34.49, 41.76 and 42.34 in L.m−2.h−1 with variable concentrations of NaCl salt solution (0.25M, 0.5M, 1M, and 2M), respectively. Also, the porosity of the membrane was increased to 47.23% with 96.87% salt rejection. The results indicate that the hydrophilicity of the nanocomposite drives them to the interface among CA and water during PI process leading to solid hydrogen bonding to achieve high water permeability. [Display omitted] • FO membranes with GQDs-MnO 2 nanocomposite are prepared targeting improved separation performance. • Solid H-bonding among nanocomposite and CA is upheld by expanded consistency of the casting solution. • Hydrophilicity of the nanocomposite drives them to the interface among CA and water. • The prepared membranes show brilliant pure water flux, reverse salt flux and high salt rejection. [ABSTRACT FROM AUTHOR]

Abstract: Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, which is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Dalton's lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications. [Copyright &y& Elsevier]

Abstract: Gluten strength is an important characteristic, determining the end product quality of durum wheat semolina. To identify the genetic basis of gluten strength in North Dakota durum cultivars, a doubled haploid population was developed from the cross of a weak gluten cultivar ‘Rugby’ and a strong gluten cultivar ‘Maier’. A framework linkage map consisting of 228 markers was constructed and used with phenotypic data on gluten strength (measured by sedimentation volume) to conduct single- and two-locus QTL analyses. Only one consistent QTL (QGs.ndsu-1B) contributing up to 90% of the phenotypic or 93% of the genotypic variation was detected on 1BS. No QTL × QTL or QTL × environment interactions were observed. The QGs.ndsu-1B was flanked by two DArT markers which were converted to STS markers and used along with SSR and EST-SSRs to develop a map of 1BS. QTL analysis delineated QGs.ndsu-1B in a 7.3 cM region flanked by an STS marker (STS-wPt2395) and a SSR marker (wmc85). The adapted background of this material and availability of PCR-based markers closely associated with this locus represent invaluable resources for marker-assisted introgression of gluten strength into other durum wheat varieties. A single QTL segregating in this population also makes it an ideal target for map-based cloning. [Copyright &y& Elsevier]

Abstract: The gene for malaria parasite cysteine protease falcipain-2B has been isolated from the Plasmodium falciparum genomic DNA. Falcipain-2B gene is located adjacent to the falcipain-2A gene on chromosome 11, and the two enzymes show extensive sequence identity at the amino acid level. Using reverse transcribed polymerase chain reaction (RT-PCR), the transcript of falcipain-2B was detected at the trophozoite stage of P. falciparum in human erythrocytes. Recombinant falcipain-2B protein expressed in bacteria exhibits protease activity as established by the cleavage of fluorescent peptide substrate as well as in-gel gelatin zymography. Importantly, the recombinant falcipain-2B cleaved host ankyrin but not protein 4.1 as assessed by the erythrocyte inside-out-vesicle assay in vitro. Notwithstanding its predicted hemoglobinase function, the P. falciparum falcipain-2B may contribute and orchestrate selective proteolytic events during the exit of malaria parasite from human red blood cells. [Copyright &y& Elsevier]

Abstract: Emp, originally detected in erythroblastic islands, is expressed in numerous cell types and tissues suggesting a functionality not limited to hematopoiesis. To study the function of Emp in non-hematopoietic cells, an epitope-tagged recombinant human Emp was expressed in HEK cells. Preliminary studies revealed that Emp partitioned into both the nuclear and Triton X-100-insoluble cytoskeletal fractions in approximately a 4:1 ratio. In this study, we report investigations of Emp in the nucleus. Sequential extractions of interphase nuclei showed that recombinant Emp was present predominantly in the nuclear matrix. Immunofluorescence microscopy showed that Emp was present in typical nuclear speckles enriched with the spliceosome assembly factor SC35 and partially co-localized with actin staining. Coimmunoprecipitation and GST-pull-down assays confirmed the apparent close association of Emp with nuclear actin. During mitosis, Emp was detected at the mitotic spindle/spindle poles, as well as in the contractile ring during cytokinesis. These results suggest that Emp undergoes dynamic rearrangements within the nuclear architecture that are correlated with cell division. [Copyright &y& Elsevier]

Malaria is a life-threatening disease of global concern. The role of nitric oxide in the clearance of malarial parasites is still under debate. Several reports suggest a possible role for nitric oxide in the protection during initial stages of malarial infection. In the present study, we demonstrate that the nitric oxide in combination with low concentrations of chloroquine controls the parasitaemia in vitro. Activated peritoneal macrophages co-cultured with lipopolysaccharide + interferon-γ or extracts from Tenospora cordifolia as an immunomodulator promoted nitric oxide production by macrophages. The high concentration of nitric oxide in combination with sub-optimal chloroquine suppressed the parasitaemia in the chloroquine resistant malarial infection. Further, the nitric oxide synthase inhibitor, NG-mono-methyl-l-arginine, downregulated nitric oxide production by peritoneal macrophages and the resulting levels of parasitaemia were higher, similar to those of untreated controls. These findings support the proposition that nitric oxide has a crucial role in the control of parasitaemia at the initial periods of blood stage malarial infection. [Copyright &y& Elsevier]

[Display omitted] To meet the requirements in air quality monitors for the public and industrial safety, sensors are required that can selectively detect the concentration of gaseous pollutants down to the parts per million (ppm) and ppb (parts per billion) levels. Herein, we report a remarkable NH 3 sensor using Ni-doped CeO 2 octahedral nanostructure which efficiently detects NH 3 as low as 45 ppb at room temperature. The Ni-doped CeO 2 sensor exhibits the maximum response of 42 towards 225 ppm NH 3 , which is ten-fold higher than pure CeO 2. The improved sensing performance is caused by the enhancement of oxygen vacancy, bandgap narrowing, and redox property of CeO 2 caused by Ni doping. Density functional theory confirms that O vacancy with Ni at Ce site (V O Ni Ce) augments the sensing capabilities. The Bader charge analysis predicts the amount of charge transfer (0.04 e) between the Ni-CeO 2 surface and the NH 3 molecule. As well, the high negative adsorption energy (≈750 meV) and lowest distance (1.40 Å) of the NH 3 molecule from the sensor surface lowers the detection limit. The present work enlightens the fabrication of sensing elements through defect engineering for ultra-trace detection of NH 3 to be useful further in the field of sensor applications. [ABSTRACT FROM AUTHOR]

• DFT for hydration of lithium ions were performed. • Lithium ion is bonded to water molecules (0–4). • The stability of the systems were studied at room temperature. • The impact of temperature was studied on the stability of each system. This work presents the results of the DFT for hydration of lithium ions in present of syringic acid and chloride ion. Herein, lithium ion is bonded to different number of water molecules (0–4) in presence of syringic acid in aqueous system. The stability of the different systems were studied at room temperature (298 K) using the thermodynamic parameters like change in Gibbs energy (Δ G), change in enthalpy (Δ H), change in energy (Δ E), energy of the system (E). Feasibility for the formation of hydrated lithium ion in presence of above moieties is studied using the DFT. Further, the impact of temperature was studied on the stability of each system i.e. at 308 and 318 K. To understand the many bodies interaction, polarization in each system is studied. Authors find that tetrahedral hydrated lithium ion with syringic acid (SA) and chloride ion has the maximum stability based on the enthalpy and Gibbs energy. Even, on changing the temperature i.e. at 308 and 318 K, tetrahedral hydrated lithium ion with SA and chloride ion is most stable. The outcome of the present work highlights the relation between the structures that used explain the intermolecular interaction between the hydration of the lithium ion and syringic acid along with chloride ion as well stability of the hydration of lithium ion. The obtained results may be valuable in determination of lithium ion on interaction with small molecules in aqueous solution. Further, TD-DFT of the stable system was studied. [ABSTRACT FROM AUTHOR]

Campylobacterjejuni causes acute diarrhea as a leading cause of morbidity and mortality in children especially in the developing countries of Asia and Africa. C.jejuni has been identified as a member of the priority pathogens category due to the sudden emergence of multidrug-resistant isolates. Therefore, it is important to develop a protective vaccine against this pathogen. In the present study, the Reverse vaccinology approach was used to identify vaccine targets from the proteome of diarrheagenic C. jejuni strain NCTC11168 for the development of chimeric vaccine candidates against C. jejuni. Pathogen proteins that have adhesin like properties and role in virulence but not present in the human host were selected for the design of a multi-epitope vaccine. MHC class I & II and B-cell epitopes present in the selected vaccine target proteins were screened using different immunoinformatics tools. The commonly predicted epitopes from their corresponding different servers were selected and further shortlisted based on their immunogenicity, antigenicity, and toxicity analysis. Shortlisted peptides were joined by GPGPG linkers to design a multi-epitope vaccine construct. Immune-modulating adjuvant monophosphoryl lipid sequence was added with the vaccine construct's N terminal using EAAAK linkers to enhance the immunogenicity. The designed vaccine construct was evaluated by antigenicity, allergenicity, solubility, and physicochemical analysis using various bioinformatics tools. A three-dimensional model of vaccine construct was modeled by the Phyre2 server and refinement by the GalaxyRefine tool. Constructed model quality was validated by the ProSA-web error-detection tool and the Ramachandran plot. After that vaccine model was docked with TLR-4 protein and complex stability confirmed by molecular dynamics simulation studies. Finally, In-silico cloning of vaccine constructs into a vector was performed to ensuring its effective expression in the microbial system. • References added in manuscript was done. • Genes and proteins nomenclature (Cjxxxx) added in the all tables and text was done. • Conservancy analysis of epitopes was done. • C. jejuni was used in place of Campylobacter jejuni after its first use in text was done. [ABSTRACT FROM AUTHOR]

In recent days, the agricultural research community is focusing on the development of different varieties of aerobic rice, as it consumes less water for its growth. In general, the yield of a crop is considered as a critical performance metric to evaluate different varieties of rice. The count of filled grains in panicles provides a measure for the yield of a crop. The evaluation of yield is a laborious, tedious process and requires human intervention. Hence, this study aims to automate the process for differentiating filled and unfilled grains of rice across different genotypes/varieties and also to help agricultural scientists in the rapid evaluation of different varieties. More precisely, this paper proposes two novel methods that involve RGB and thermal images: (a) Discrimination based on RGB Images (DRI) (b) Discrimination based on Thermal Images (DTI). The study of proposed methods on 15 rice-panicles of different genotypes indicates that DRI method, which involves colour of grains, is found to be challenging to discriminate between filled and unfilled grains. Whereas, DTI method, which makes use of thermal images in differentiating filled and unfilled grains, is found to be profoundly convenient. The performance analysis demonstrates that the proposed DTI method, with averaged absolute errors (AAEs) in discriminating filled grains (2.66 %) and unfilled grains (11.389 %), outperforms the proposed DRI method with an AAEs in discriminating filled grains (10.664 %) and unfilled grains (34.296 %). The present investigation resulted in the development of DTI method to discriminate against the filled and unfilled grains across genotypes, and it can be used in rice improvement programs in the future. Image 1 • RGB images were analysed to discriminate filled and unfilled grains of rice. • RMSEs of DRI method are 5.556 (filled) and 5.675 (unfilled) in discrimination. • Temperature of unfilled grains drops at a faster rate than that of filled grains. • DTI method outperformed DRI method in discriminating filled and unfilled grains. • RMSEs of DTI method are 1.844 (filled) and 1.880 (unfilled) in discrimination. [ABSTRACT FROM AUTHOR]

Adipose-Derived Stem Cells (ADSCs) have an important contribution in regenerative medicine ranging from testing stem cell therapy for disease treatment in pre-clinical models to clinical trials. For immediate use of stem cells for therapy, there is a requirement of the high dose of stem cells at different time points which can be met by cryopreservation. In this study, we evaluated the characteristics of long-term cryopreserved ADSCs and their regenerative potential after an average of twelve-year cryopreservation. Revived ADSCs were examined for cell viability and proliferation by trypan blue, Calcein/Hoechst and MTT assay. Expression of stem cell markers was examined by flow cytometry, immunostaining and qPCR. Colony forming efficiency and spheroid formation ability were also assessed. Multilineage differentiation potential was evaluated by induction into osteocytes, adipocytes, neural cells, corneal keratocytes and trabecular meshwork (TM) cells. Post-thaw, ADSCs maintained expression of stem cell markers CD90, CD73, CD105, CD166, NOTCH1, STRO-1, ABCG2, OCT4, KLF4. ADSCs retained colony and spheroid forming potential. These cells were able to differentiate into osteocytes, confirmed by Alizarin Red S staining and elevated expression of osteocalcin and osteopontin; into adipocytes by Oil Red O staining and elevated expression of PPARγ2. ADSCs could differentiate into neural cells, stained positive to β-III tubulin, neurofilament, GFAP as well as elevated expression of nestin and neurofilament mRNAs. ADSCs could also give rise to corneal keratocytes expressing keratocan, keratan sulfate, ALDH and collagen V, and to TM cells expressing CHI3L1 and AQP1. Differentiated TM cells responded to dexamethasone treatment with increased Myocilin expression, which could be used as in vitro glaucoma model for further studies. Conditioned medium from ADSCs was found to impart a regenerative effect on primary TM cells. In conclusion, ADSCs maintained their stemness and multipotency after long-term cryopreservation with variability between different donors. This study can have great repercussions in regenerative medicine and pave the way for future clinical trials using cryopreserved ADSCs. Image 1 • ADSCs were cryopreserved for ~12 years and regenerative potential was observed. • Post thaw, ADSCs maintained stemness as well as cell viability. • Cryo-ADSCs were able to differentiate into multiple lineage cell types. • Cryo-ADSCs gave rise to corneal keratocytes and trabecular meshwork cells. • ADSC conditioned media induced trabecular meshwork cell regeneration. [ABSTRACT FROM AUTHOR]

Graphical abstract The illustration depicts the favorable interaction initiated by introduction of a potential therapeutic bioorganic luminophore from the class of Azapodophyllotoxin into the sudlow site I of human serum albumin and its ability to regulate the innate rotamers of Trp-214 residue in Human Serum Albumin. Highlights • Adaptation of therapeutic luminophore Azapodophyllotoxin into sudlow site I of HSA. • Electrostatic & hydrophobic interaction are major factors into adapting HPFQ. • Minor perturbation occurs in secondary structure of malleable sudlow site I of HSA. • Molecular docking assists to establish the close proximity of HPFQ to Trp-214. • Exploration of FRET mechanism between HPFQ and Trp-214 of HSA. • HPFQ regulates the emissive population of three rotamers of Trp-214 in HSA. Abstract Human serum albumin is perceived to be the most abundant protein in human blood plasma and functions as a major carrier of different enzymes and drugs inside human body. The present article puts in an effort to demonstrate the attitude adopted by human serum albumin towards a potential therapeutic luminophore 4-(2-Hydroxyethyl)-10-phenyl-3,4,6,7,8,10-hexahydro-1H-cyclopenta[ g ]furo[3,4-b]quinoline-1-one (HPFQ). HPFQ is a prodigy from azapodophyllotoxin class of compounds, which have been synthesized from the perspective of improved bioactivity than its prologue podophyllotoxins. While, HPFQ has proved to be highly bioactive against most cancer cell lines with best GI 50 values of <0.1 µM for a major number of cell lines; it also showed terrific fluorescent properties throughout the polarity scale, worthy of a promising imaging agent. The binding mechanism of HPFQ with HSA has been established by combining in vitro spectroscopic techniques, in silico molecular docking and induced fit docking (IFD). The competitive site-binding studies demonstrated that the otherwise anion-receptor sudlow site I of HSA nurtures neutral HPFQ with prudent affinity (Binding constant, K b = 0.74 × 105 M−1). The time-resolve fluorescence studies reveal an appreciable reduction in HSA average radiative lifetime against an increase in HPFQ concentration and provided evidence for Forster's resonance energy transfer (FRET) being responsible for the dominant quenching mechanism, escorted by minor structural deformations in the backbone of protein structure. HPFQ institutes itself near Trp-214 within protein matrix, and subsequently the "hydrophobic amino acids" dominated cybotactic environment of Trp-214 experiences a reduction in the micropolarity. The allosteric modulation triggered by the stronger association of HPFQ with HSA leads towards minor deformation in secondary structure of protein. Sudlow site I of HSA proficiently embraces a favourable conformation like malleable dough to furnish space for arriving bioactive HPFQ molecule. HPFQ is also believed to administer the conformational regulation in HSA domain by affecting inter-conversion of HSA rotamers, which may prove to be an enlightening area to decode the preferable interaction between them. The juxtaposed spectroscopic research described herein is expected to embolden design of azapodophyllotoxin based anti-proliferative clinical agents for efficient in vivo bio-distribution employing HSA-centred drug delivery and administration systems. [ABSTRACT FROM AUTHOR]

Adjuvant enhancing mucosal immune response is preferred in controlling many pathogens at the portal of entry. Earlier, we reported that a toll-like-receptor 7 (TLR7) agonist, resiquimod (R-848), stimulated the systemic immunity when adjuvanted with the inactivated Newcastle disease virus vaccine in the chicken. Here, we report the effect of R-848 when adjuvanted with live or inactivated avian infectious bronchitis virus (IBV) vaccines with special emphasis on mucosal immunity. Specific pathogen free (SPF) chicks (n = 60) were equally divided into six groups at two weeks of age and immunized with either inactivated or live IBV vaccine adjuvanted with or without R-848. Groups that received either PBS or R-848 served as control. A booster was given on 14 days post-immunization (dpi). R-848 enhanced the antigen specific humoral and cellular immune responses when co-administered with the vaccines as evidenced by an increase in the antibody titre in ELISA and stimulation index in lymphocyte transformation test (LTT) till 35 dpi and increased proportion of CD4 + and CD8 + T cells on 21 dpi in the flow cytometry. Interestingly, it potentiated the IgA responses in the tear and intestinal secretions when used with both live and inactivated IBV vaccines. The combination of IBV vaccine with R-848 significantly up-regulated the transforming growth factor beta 4 (TGFβ4) transcripts in the peripheral blood mononuclear cells (PBMCs) than that of the respective vaccine per se . An enhanced secretory IgA response is likely due to the up-regulation of TGFβ4, which is responsible for class switching to IgA. In conclusion, co-administration of R-848 with inactivated or live IBV vaccine enhanced the systemic as well as mucosal immune responses in the chicken. [ABSTRACT FROM AUTHOR]

Abstract: The present investigation was undertaken to study if curcumin, which is recognized for its potential as an antineoplastic and immunopotentiating agent, can also influence the process of myelopoiesis in a tumor-bearing host. Administration of curcumin to tumor-bearing host augmented count of bone marrow cell (BMC) accompanied by an up-regulated BMC survival and a declined induction of apoptosis. Curcumin administration modulated expression of cell survival regulatory molecules: Bcl2, p53, caspase-activated DNase (CAD) and p53-upregulated modulator of apoptosis (PUMA) along with enhanced expression of genes of receptors for M-CSF and GM-CSF in BMC. The BMC harvested from curcumin-administered hosts showed an up-regulated colony forming ability with predominant differentiation into bone marrow-derived macrophages (BMDM), responsive for activation to tumoricidal state. The number of F4/80 positive bone marrow resident macrophages (BMM), showing an augmented expression of M-CSF, was also augmented in the bone marrow of curcumin-administered host. In vitro reconstitution experiments indicated that only BMM of curcumin-administered hosts, but not in vitro curcumin-exposed BMM, augmented BMC survival. It suggests that curcumin-dependent modulation of BMM is of indirect nature. Such prosurvival action of curcumin is associated with altered TH1/TH2 cytokine balance in serum. Augmented level of serum-borne IFN-γ was found to mediate modulation of BMM to produce enhanced amount of monokines (IL-1, IL-6, TNF-α), which are suggested to augment the BMC survival. Taken together the present investigation indicates that curcumin can potentiate myelopoiesis in a tumor-bearing host, which may have implications in its therapeutic utility. [Copyright &y& Elsevier]

Abstract: Erythroblast macrophage protein (Emp) mediates the attachment of erythroid cells to macrophages and is required for normal differentiation of both cell lineages. In erythroid cells, Emp is believed to be involved in nuclear extrusion, however, its role in macrophage differentiation is unknown. Information on the changes in the expression level and subcellular distribution of Emp in differentiating macrophages is essential for understanding the function of Emp. Macrophages of varying maturity were examined by immunofluorescence microscopy and biochemical methods. Our data show that Emp is expressed in all stages of maturation, but its localization pattern changes dramatically during maturation: in immature macrophages, a substantial fraction of Emp is associated with the nuclear matrix, whereas in more mature cells, Emp is expressed largely at cell surface. Pulse-chase experiments show that nascent Emp migrates intracellularly from the cytoplasm to the plasma membrane more efficiently in mature macrophages than in immature cells. Incubation of erythroid cells with macrophages in culture shows that erythroid cells attach to mature macrophages but not to immature macrophage precursors. Together, our data show that the temporal and spatial expression of Emp correlates with its role in erythroblastic island formation and suggest that Emp may be involved in multiple cellular functions. [Copyright &y& Elsevier]

The current study intended to optimize the concentration of Oxyrase in the semen dilutor and to evaluate its effect on freezability of spermatozoa of Sahiwal bulls. Supplementation of Oxyrase at 0.125 IU/mL concentration significantly reduced dissolved oxygen (DO) in the dilutor to 4 ppm in 16–18 min at 35 °C. For supplementation studies, a total of 24 ejaculates were categorized into poor and good ejaculates categories (n = 12 each) based on their initial progressive motility. Each ejaculate was further divided into two aliquotes. The first aliquote was diluted with tris-egg yolk extender without Oxyrase (control group) whereas, in the treatment group, Oxyrase was supplemented at the concentration of 0.125 IU/mL of extender. The parameters evaluated include cholesterol and plasma membrane phospholipids (PMP) at fresh, while IPM, acrosomal and plasma membrane integrity, cholesterol, PMP and oxidative stress parameters like lipid peroxidation (LPO), total antioxidant capacity (TAC) and reactive oxygen species (ROS) were evaluated at pre-freeze and post-thaw stages. The IPM and acrosomal intactness were higher (p < 0.05) in treatment group at post-thaw stage in good ejaculates. Oxyrase supplementation resulted in lower (p < 0.05) cholesterol leakage in both categories and lower (p < 0.05) LPO in good ejaculates at post-thaw stage. No statistical difference in ROS was observed between control and treatment groups at all stages whereas, level of TAC was higher (p < 0.05) in the treatment group compared to control group at post-thaw stage of both categories. Therefore, Oxyrase as an oxygen scavenging agent could preserve the post-thaw quality of Sahiwal bull spermatozoa. [ABSTRACT FROM AUTHOR]

The aim of this study was to understand the role of anaerobic regulator FNR (Fumarate Nitrate Reduction) in Salmonella Typhimurium through proteomic approach. We did label free quantitative proteomic analysis of Salmonella Typhimurium PM45 wild type and the fnr null mutant cultured under anaerobic conditions. The data revealed 153 significantly differentially expressed proteins (DEPs) in the mutant out of 1798 total proteins identified. Out of 153 DEPs, 94 proteins were up-regulated (repressed by FNR) and 59 proteins were down-regulated (activated by FNR) in the mutant. The network analysis indicated up-regulation of TCA cycle, electron transport chain and ethanolamine metabolism and down regulation of pyruvate metabolism and glycerol and glycerophospholipid metabolism. Our study showed that FNR represses ethanolamine utilization. The different metabolic pathways such as pyruvate metabolism, glycerol metabolism and glycerophospholipid metabolism were activated by FNR. Further, FNR positively regulated the DNA binding protein Fis, one of the global regulators of virulence in Salmonella Typhimurium. Thus, our finding highlights the pivotal role of FNR in regulating bacterial metabolism and virulence during anaerobiosis for systemic infection of the host. • Here we compared proteome of S. Typhimurium WT and Δ fnr mutant during anaerobiosis. • Our study provided the first report of repression of ethanolamine utilization by FNR. • First time, we found that FNR activated pyruvate metabolism, Glycerol metabolism. • FNR activated GlpQ, a key enzyme of Glycerophospholipid metabolism. • FNR positively regulated Fis, a global regulator of virulence in S. Typhimurium. [ABSTRACT FROM AUTHOR]

The molecular mechanism of the underlying genes involved in the process of fruit ripening in Capsicum (family Solanaceae) is not clearly known. In the present study, we identified orthologs of 32 fruit development/ripening genes of tomato in Capsicum , and validated their expression in fruit development stages in C. annuum , C. frutescens , and C. chinense. In silico expression analysis using transcriptome data identified a total of 12 out of 32 genes showing differential expression during different stages of fruit development in Capsicum. Real time expression identified gene LOC107847473 (ortholog of MADS-RIN) had substantially higher expression (>500 folds) in breaker and mature fruits, which suggested the non-climacteric ripening behaviour of Capsicum. However, differential expression of Ehtylene receptor 2-like (LOC107873245) gene during fruit maturity supported the climacteric behaviour of only C. frutescens (hot pepper). Furthermore, development of 49 gene based simple sequence repeat (SSR) markers would help in selection of identified genes in Capsicum breeding. • We identified orthologs of 32 fruit development/ripening genes of tomato in Capsicum • In silico expression analysis using transcriptome data identified a total of 12 genes differentially expressed during different stages of fruit development in Capsicum. • Real time expression identified gene LOC107847473 (ortholog of MADS-RIN) had substantially higher expression (>500 folds) in breaker and mature fruits. • 49 gene based simple sequence repeat (SSR) markers were also developed. [ABSTRACT FROM AUTHOR]

Protein translocating Cag type IV secretion system of Helicobacter pylori is a diverse multi-protein complex. Here, we have characterized one of its key subunit CagW to identify its interacting partners. Our results demonstrate for the first time that this VirB6 homologue interacts with the substrate of the secretion system CagA. CagW forms multimer and its absence affects cellular levels of pilus forming components, CagL, CagI and CagH. Our results support the notion that the protein is essential for the transport of CagA across the bacterial membrane barrier and would aid in improving our understanding of structural and functional aspects of the inner membrane part of Cag-T4SS channel complex for the passage of substrate CagA. • CagW, a VirB6 homologue interacts with Cag-T4SS substrate CagA. • CagW forms multimer. • Cellular levels of pilus components CagL, CagI and CagH are cagW dependent. [ABSTRACT FROM AUTHOR]

Abstract Rational designing of metal-free carbon nitride based photocatalysts can lead to an excellent optical response and a higher photocatalytic activity driven by visible and solar light. This combines green photocatalytic technology with greener materials prepared by facile approaches for environmental remediation. Herein we report utilization of star photocatalyst g-C 3 N 4 (CN) to form highly efficient hetero-assemblies along with acidified g-C 3 N 4 (ACN), polyaniline (PANI), reduced graphene oxide (RGO) and biochar. By use of these organic semiconductors we synthesize g-C 3 N 4 /ACN/RGO@Biochar (GARB), g-C 3 N 4 /PANI/RGO@Biochar (GPRB) and ACN/PANI/RGO@Biochar (APRB) nano-assemblies with different optical response and band edge positions for a better charge flow and reduced recombination of carriers. These synthesized catalysts were used for visible light powered degradation of 2,4-Dichlorophenoxy acetic acid (2,4-D) and ibuprofen (IBN). APRB performs the best and degrades 99.7% and 98.4% of 2,4-D and IBN (20 mg L−1) under Xe lamp exposure in 50 min and retention of high activity in natural sunlight. Optical analysis, photoelectrochemical response and radical quenching studies show both hydroxyl and superoxide radical anions as major reactive species and a Z-scheme photocatalytic mechanism. RGO acts as an electron mediator and protects higher positioned bands of PANI and ACN in APRB for a remarkable photocatalytic activity for a metal free material. The degradation pathway was analyzed by LC-MS analysis and 42% and 40% total organic carbon was removed in 2 h for 2,4-D and IBN degradation respectively. The toxicity of degraded products was analyzed by analyzing viability of human peripheral blood cells with retaining of 99.1% cells. Graphical abstract Image 1 Highlights • Metal free organic semiconductors based nano-assemblies as photocatalysts. • Utilizing g-C 3 N 4 , acidified C 3 N 4 , PANI for designing efficient photocatalyst. • Z-scheme mechanism-high spectral response and charge separation. • Excellent photo-degradation of Ibuprofen and 2,4-D under artificial and solar light. • Complete mineralization and no toxicity on human PBL cells. [ABSTRACT FROM AUTHOR]

Highlights • Soluble amyloid beta (sAβ 1-42) plays a dual role in the process of inflammation. • sAβ 1-42 activates NLRP3 inflammasome on the one hand and suppresses the secretion of TNF-α on the other hand. • sAβ 1-42 may have protective role in the brain against inflammatory damage. Abstract Deposition of amyloid-β in Alzheimer's disease is accompanied by chronic inflammation, which involves raised levels of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β. However, the role of Aβ 1 - 42 in the inflammatory process, before it gets deposited into aggregates has not been investigated thoroughly. Through this study, we are illustrating the dual role of soluble Aβ 1 - 42 (sAβ 1-42) in activating the NLRP3 inflammasome and simultaneously inhibiting TNF-α secretion. Our data suggested that the treatment of chronically induced THP-1 macrophages and N9 microglial cells with sAβ 1 - 42 can suppress the major inflammatory cytokine TNF-α without affecting the level of IL-6. However, the activation of NLRP3 inflammasome was well evidenced by secretion of IL-1β, increased expression of NLRP3 and caspase-1, implicating sAβ 1 - 42 in enhancing and suppressing one or other type of inflammation. Further investigation revealed that sAβ 1 - 42 was able to severely abrogate the expression of NF-κB, p50 and restricting the translocation of NF-κB, p65 to nucleus by inhibiting phosphorylation of IκB-α in THP-1 macrophages. These data indicate that the sAβ 1 - 42 may play a dual role during inflammatory process, wherein, it may be involved in protecting the cells from inflammatory damage due to TNF-α. This ability of sAβ 1 - 42 might be playing some role in protecting the brain cells during the process of aging and Alzheimer's disease, where, chronic inflammatory environment plays a vital role. [ABSTRACT FROM AUTHOR]

Cyanobacteria, also known as blue green algae are one of the important ubiquitous oxygen evolving photosynthetic prokaryotes and ultimate source of nitrogen for paddy fields since decades. In past two decades, indiscriminated use of pesticides led to biomagnification that intensively harm the structure and soil functions of soil microbes including cyanobacteria. Cyanobacterial abundance biomass, short generation, water holding capacity, mineralizing capacity and more importantly nitrogen fixing have enormous potential to abate the negative effects of pesticides. Therefore, investigation of the ecotoxicological effects of pesticides on the structure and function of the tropical paddy field associated cyanobacteria is urgent and need to estimate the fate of interaction of pesticides over nitrogen fixations and other attributes. In this regard, comprehensive survey over cyanobacterial distribution patterns and their interaction with pesticides in Indian context has been deeply reviewed. In addition, the present paper also deals the molecular docking pattern of pesticides with the nitrogen fixing proteins, which helps in revealing the functional interpretation over nitrogen fixation process. [ABSTRACT FROM AUTHOR]

Abstract Visceral leishmaniasis (VL) is a disease caused by protozoan species of the genus Leishmania and is transmitted through bites from the Phlebotomus sand fly; it is associated with considerable morbidity and mortality in many parts of world, including India. Reports on the protective role played by saliva proteins of Lutozomyia longipalpis, Phlebotomus papatasi and Phlebotomus duboscqi. are available. However, no studies have explored the salivary proteins of P. argentipes , which is the known proven vector for the transmission of VL in the Indian sub-continent. Herein we revealed the presence of two proteins of 14.2 and one protein of 13.6 kDa in Indian strain P. argentipes which is absolute identical to previously reported protein of SP15 family (PagSP01, PagSP02 and PagSP07) of P. argentipes of NIH colony, USA. In an experimental study on P. argentipes from Bihar, India, we demonstrated that a strong humoral and cellular immune response was triggered to reduce the concomitant Leishmania load in groups of immunized mice. The immunized group produced a considerable amount of IgG antibodies, and their splenocytes generated TH1 cytokines (IL-12, IFN-γ) with the support of delayed-type hypersensitivity (DTH) reactivity in such mice at the challenged site. We summarize from our data that some identical proteins to previous from SP15 family protein of 14.2 and 13.6 kDa molecular size, derived from Indian P. argentipes and reported its first time, can also be significant in resolution of VL infection after modulation of host protective T cell response in VL. [ABSTRACT FROM AUTHOR]

Evidences demonstrate that metabolic inhibitor 3-bromopyruvate (3-BP) exerts a potent antitumor action against a wide range of malignancies. However, the effect of 3-BP on progression of the tumors of thymic origin remains unexplored. Although, constituents of tumor microenvironment (TME) plays a pivotal role in regulation of tumor progression, it remains unclear if 3-BP can alter the composition of the crucial tumor growth regulatory components of the external surrounding of tumor cells. Thus, the present investigation attempts to understand the effect of 3-BP administration to a host bearing a progressively growing tumor of thymic origin on tumor growth regulatory soluble, cellular and biophysical components of tumor milieu vis-à-vis understanding its association with tumor progression, accompanying cell cycle events and mode of cell death. Further, the expression of cell survival regulatory molecules and hemodynamic characteristics of the tumor milieu were analysed to decipher mechanisms underlying the antitumor action of 3-BP. Administration of 3-BP to tumor-bearing hosts retarded tumor progression accompanied by induction of tumor cell death, cell cycle arrest, declined metabolism, inhibited mitochondrial membrane potential, elevated release of cytochrome c and altered hemodynamics. Moreover, 3-BP reconstituted the external milieu, in concurrence with deregulated glucose and pH homeostasis and increased tumor infiltration by NK cells, macrophages, and T lymphocytes. Further, 3-BP administration altered the expression of key regulatory molecules involved in glucose uptake, intracellular pH and tumor cell survival. The outcomes of this study will help in optimizing the therapeutic application of 3-BP by targeting crucial tumor growth regulatory components of tumor milieu. [ABSTRACT FROM AUTHOR]

In the present research pathology and molecular diagnosis of elephant endotheliotropic herpes virus-haemorrhagic disease (EEHV-HD) among Asian elephants was studied. Out of 76 cases, 20 were positive for EEHV infection in PANPOL and POL1 based semi-nested PCR. Out of 20 samples, 10 samples were fatal cases of EEHV-HD while 10 were of either subclinical or latent infection. Acute onset haemorrhagic disease with EEHV-HD had anorexia, facial and neck swelling, cyanotic buccal mucosa and tongue, nasal and ocular discharge, and colic. The hallmark of gross finding in all cases were severe haemorrhagic lesions in the internal organs viz. cyanosis of tongue with multifocal petechial haemorrhages, diffuse epicardial and endocardial haemorrhages, swollen liver (rounded edges) with parenchymal haemorrhages, serosal and mucosal haemorrhages in gastrointestinal tract, congested kidneys with corticomedullary haemorrhages, highly congested meninges, and brain capillaries with haemorrhages. Microscopic findings in all the cases had severe vascular changes in the visceral organs. Microthrombi was present in the vasculature of tongue, heart, lung, liver, kidney, and brain. The endothelial lining of most of the blood vessels were swollen with apoptotic changes. Amphophilic to basophilic intranuclear inclusion bodies were observed in the endothelial cells. Immunostaining using anti-EEHV DNAPOL hyperimmune sera revealed intense positive signals in the endothelium of blood vessels and their walls. Quantification of viral load in necropsy tissue samples revealed highest in the heart (7.4 × 106/μg of sample) and least in the brain (9 × 103/μg of sample). The PCR amplicons from EEHV1 specific genes (POL1(U38) and TER were subjected to partial genome sequencing which had 99.9% similarity with the EEHV1A subtype. It was concluded that Asian elephants in India are latently infected for EEHV1 and in all the fatal EEHV-HD cases, EEHV1A subtype was the causative agent with characteristic pathomorphological changes in visceral organs. • EEHV-HD occurs among captive and free-ranging Asian elephants in India. • Endotheliotropic nature of the virus leads to acute vascular changes and microthrombi formation in visceral organs. • EEHV1A is the predominant subtype circulating among Asian elephants in India. [ABSTRACT FROM AUTHOR]

Context An extensive body of literature indicates a relationship between insulin resistance and the up-regulation of the kynurenine pathway, i.e. the preferential conversion of tryptophan to kynurenine, with subsequent overproduction of diabetogenic downstream metabolites, such as kynurenic acid. Case description We have measured the concentration of kynurenine pathway metabolites (kynurenines) in the brain and pancreas of two young (27 and 28 yrs) insulin resistant, normoglycemic subjects (M-values 2 and 4 mg/kg/min, respectively) using quantitative C-11-alpha-methyl-tryptophan PET/CT imaging. Both subjects underwent a preventive 12-week metformin treatment regimen (500 mg daily) prior to the PET/CT study. Whereas treatment was successful in one of the subject (M-value increased from 2 to 12 mg/kg/min), response was poor in the other subjects (M-value changed from 4 to 5 mg/kg/min). Brain and pancreas concentrations of kynurenines observed in the responder were similar to that in a healthy control subject, whereas kynurenines determined in the non-responder were about 25% higher and similar to those found in a severely insulin resistant patient. Consistent with this outcome, M-values were negatively correlated with both kynurenic acid levels (R 2 = 0.68, p = 0.09) as well as with the kynurenine to tryptophan ratio (R 2 = 0.63, p = 0.11). Conclusion The data indicates that kynurenine pathway metabolites are increased in subjects with insulin resistance prior to overt manifestation of hyperglycemia. Moreover, successful metformin treatment leads to a normalization of tryptophan metabolism, most likely as a result of decreased contribution from the kynurenine metabolic pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • ROFDTS deployed successfully in Indus-2 synchrotron radiation source. • ROFDTS measures the temperature profile of a 160 m long power supply cable (current 760 A, DC) of dipole magnets. • ROFDTS can also detect the progress of unforeseen fire events anywhere in the cable. • The sensing fiber of ROFDTS could survive in the harsh environment of Indus-2. • Mapping of various dipoles is provided on the temperature profile curve. The paper presents the work on development and application of Raman optical fiber distributed temperature sensor (ROFDTS). ROFDTS has been used for monitoring the temperature profile and detecting the progress of unforeseen fire events anywhere in a 160 m long power supply cable (current 760 A, DC) of dipole magnets in the Indus-2 synchrotron radiation source (SRS). Indus-2 is a national facility and is being operated in round the clock mode. The sensing fiber could survive in the harsh environment of Indus-2 SRS that consists of bremsstrahlung radiation of 6.7 Rad/h, high magnetic field of 1.5 T and radio frequency (RF) field of 1.27 MV at 505.812 MHz. The fire detecting capability of ROFDTS was first tested on the mock test setup in the laboratory by artificially creating the four hot zones. Each hot zone has the width of 1.0 m in the sensing fiber at the spatial locations of 26 m, 48 m, 70 m and 92 m respectively. An audio-visual alarm was generated when the temperature of the hot zones exceeded the set temperature limit of 50 °C within 30 s of the start of the fire. Finally, ROFDTS system was deployed to measure the temperature profile of power supply cable during 'no operation', 'injection' of the electron beam current (109 mA with the energy of electrons @ 550 MeV) and at 'normal operation' of the electron beam current (145 mA with the energy of electrons @ 2.5 GeV) in Indus-2 SRS. The peak temperature of power cable reached from 26 °C to 44 °C from 'no operation' to during the 'normal operation' condition of the Indus-2 SRS. [ABSTRACT FROM AUTHOR]

Hydroxyurea (HU) is the key drug to treat Sickle cell anemia (SCA). However, its treatment is associated with the liability of myelosuppression. The present study aimed to investigate the potential of epicatechin as a supplementation therapy for the symptomatic management of SCA under HU therapy. A panel of experiments were performed at first to observe epicatechin's effect on sickling and hemolytic behaviour using SCA patient's blood (ex vivo). Thereafter, the effect of HU in the presence or absence of epicatechin was investigated on cytokine inhibition in rat splenocytes (ex vivo) as well as alterations in hematological parameters and kidney function tests in rats (in vivo). Then, any effect of epicatechin on pharmacokinetic modulation of HU in rats was elucidated along with the underlying mechanism using a battery of in vitro and in vivo models. Epicatechin exhibited potent action on anti-sickling, polymerization inhibition, and erythrocyte membrane stability. It did not show any inherent hemolytic activity and reduced TNF-α level during concomitant administration with HU. Based on hematological changes in rats, epicatechin treatment aided to the beneficial effect of HU and prevented the treatment-linked disadvantageous effects of HU like neutropenia. The plasma exposure of HU was significantly augmented in rats upon simultaneous oral administration of epicatechin with HU. Down-regulation of Oatp1b2 and catalase possibly contributed to the pharmacokinetic interaction of HU. Epicatechin is found to be a promising candidate and should be explored at a reduced dose level of HU towards offsetting the dose-dependent myelosuppressive effect of HU under the frame of supplementation therapy in SCA. [Display omitted] • Epicatechin have significant attributes to counteract myelosuppression. • First report of epicatechin for its anti-sickling action using SCA patient's blood. • Epicatechin augmented oral exposure of hydroxyurea by modulating Oatp1b2 and catalase. • Epicatechin have substantial potential for supplementation therapy in SCA. [ABSTRACT FROM AUTHOR]

How recoding of fnr , an anaerobic regulatory gene, affects pathogenicity related parameters of Salmonella Typhimurium (STM). The fnr gene was recoded by substituting all of it's codons with synonymous rare codons of STM. Recoding fnr gene severely reduced the ability of the recoded mutant to compete with wild strain under nutrient depletion condition. Mutants were also less motile than the wild strain and their biofilm forming ability was significantly decreased as compared to wild strain. The recoded strain showed significant reduced survival within murine macrophages (RAW264.7) and monocyte derived macrophage of poultry origin. The colonisation ability of recoded mutant in liver and spleen of mice on day 5 of post infection was significantly reduced. The recoded strain exhibited significant reduction in faecal shedding on day 1 and 5 after infection. Our study showed that recoding the anaerobic regulator fnr of STM significantly compromised its growth, decreased motility, biofilm forming ability and survival within macrophages. Further, the recoded fnr strain showed reduced colonisation ability and faecal shedding in mice. Thus, these findings highlight that recoding the global anaerobic regulator fnr of Salmonella Typhimurium attenuates its pathogenicity. • Here we recoded fnr, an anaerobic regulator, by substituting all of it's codons with synonymous rare codons of Salmonella Typhimurium. • First time we found that recoding fnr significantly compromised its growth, decreased motility, biofilm forming ability and survival within macrophages. • The recoded fnr strain also showed reduced colonisation ability and faecal shedding in mice thus making the recoded fnr mutant a potential vaccine candidate. [ABSTRACT FROM AUTHOR]

A comprehensive study on the pathogenicity and host immune response was conducted in White Pekin ducklings after experimental infection with an Indian isolate of duck enteritis virus (DEV). The virus was found to be highly pathogenic and pantropic, which rapidly multiplied in various organs, mainly in the spleen and liver showing higher viral load with severe pathological lesions and caused 100% mortality. Expression profiles of immune gene transcripts in tissues (liver, spleen, brain) revealed upregulation of proinflammatory cytokines IFN-α, IFN- β, IL-1β, IL-6 and also iNOS with stimulation of TLRs (TLR-2, 3, 21). IFN-α was robustly upregulated (p < 0.05) especially in liver, might be playing role in antiviral innate immunity. Further, massive upregulation of MHC class-I (p < 0.01), expression of Th1 cytokines (IFN-γ & IL-2) and certain Th2 cytokines (IL-4 & IL-10) suggests stimulation of cell mediated as well as humoral immunity. To our knowledge, we are reporting first time about the robust upregulation of MHC class-I in spleen, liver and brain along with expression of certain cytokines in the peripheral blood mononuclear cells (PBMCs) during experimental DEV infection. • DEV infection induced predominantly IFN-α and other proinflammatory cytokines. • Upregulation of MHC class-I and Th1 cytokines (IFN-γ, IL-2) indicated predominant cell mediated immunity. • Induction of IL-4 is suggestive of Th2 mediated immune response in duck plague. [ABSTRACT FROM AUTHOR]

[Display omitted] • Triazole linked tacrine glycoconjugates were synthesized as Acetylcholinesterase inhibitors. • In-silico hepatotoxicity was predicted via crystal structure of CYP1A2, showing no affinity for enzyme. • Compounds- A-1, A-3, A-4, A-7 showed more than 90% inhibition at 10 µM. • Kinetics and molecular docking studies revealed that A-1 is a mixed type inhibitor. • A-1/AChE complex was quite stable during molecular simulations of A-1. Tacrine is a known Acetylcholinesterase (AChE) inhibitors having hepatotoxicity as main liability associated with it. The present study aims to reduce its hepatotoxicity by synthesizing tacrine linked triazole glycoconjugates via Huisgen's [3 + 2] cycloaddition of anomeric azides and terminal acetylenes derived from tacrine. A series of triazole based glycoconjugates containing both acetylated (A-1 to A-7) and free sugar hydroxyl groups (A-8 to A-14) at the amino position of tacrine were synthesized in good yield taking aid from molecular docking studies and evaluated for their in vitro AChE inhibition activity as well as hepatotoxicity. All the hybrids were found to be non-toxic on HePG2 cell line at 200 μM (100 % cell viability) as compared to tacrine (35 % cell viability) after 24 h of incubation period. Enzyme kinetic studies carried out for one of the potent hybrids in the series A-1 (IC 50 0.4 μ M) revealed its mixed inhibition approach. Thus, compound A-1 can be used as principle template to further explore the mechanism of action of different targets involved in Alzheimer's disease (AD) which stands as an adequate chemical probe to be launched in an AD drug discovery program. [ABSTRACT FROM AUTHOR]

Abstract: Dectin-1, is a type II transmembrane receptor protein which contains a single extracellular CTLD (C-type lectin domain), stalk, transmembrane domain and an ITAM (immunoreceptor tyrosine-based activation motifs) in its cytoplasmic tail. Dectin-1 has the ability to recognize fungal β-glucans, which are carbohydrate PAMPs found predominantly in fungal cell walls. The recognition of fungal β-glucans by Dectin-1 helps in a variety of cellular responses, like host protection, such as fungal uptake and killing, and the production of inflammatory cytokines and chemokines. In this study we predicted the 3D (three dimensional) structure of Dectin-1 receptor based on homology modeling using MODELLER 9v8 software. The TMHMM server was used for the prediction of transmembrane helices. DALI, PROFUNC, Q-Site Finder, PINTS servers and PASS software used for the prediction of functional sites in the modeled Dectin-1 receptor. The docking investigation of Dectin-1 receptor with β-glucan suggests that ASP150, ASP113, GLY106, and GLU196 amino acids are the catalytic residues which form a shallow groove in the protein surface and bind to ligand β-glucan. We hope that this work will help in in-silico screening, structure-based design, and in understanding the structural basis of ligand binding to the Dectin-1 receptor. [Copyright &y& Elsevier]

NLRP3 inflammasome is involved in several chronic inflammatory diseases. The inflammatory effect of the NLRP3 inflammasome is executed through IL-1β and IL-18. Therefore, IL-1β is one of the primary targets in chronic inflammatory conditions. However, current treatment regimens are dependent on anti- IL-1β biologicals. The therapies targeting IL-1β through inhibition of NLRP3 inflammasome are thus being actively explored. We identified safranal, a small molecule responsible for the essence of saffron as a potential inhibitor of the NLRP3 inflammasome. Safranal significantly suppressed the release of IL-1β from ATP stimulated J774A.1 and bone marrow-derived macrophages (BMDMs) by regulating CASP1 and CASP8 dependent cleavage of pro-IL-1β. Safranal markedly suppressed the expression of NLRP3 and its ATPase activity. Safranal treatment enhanced the expression of NRF2, whereas, si-RNA mediated silencing of Nrf2 abrogated the anti-NLRP3 effect of safranal. Furthermore, safranal inhibited ASC oligomerization and formation of ASC specks. Safranal also displayed anti-NLRP3 activity in multiple mice models. Treatment of animals with safranal reduced the production of IL-1β in ATP elicited peritoneal inflammation, MSU induced air pouch inflammation, and MSU injected foot paw edema in mice. Thus, our data projects safranal as a potential preclinical drug candidate against NLRP3 inflammasome triggered chronic inflammation. [Display omitted] • Safranal inhibits extracellular ATP induced NLRP3 inflammasome activation in vitro. • Safranal inhibited both caspase-1 and caspase-8 to repress processing of IL-1β. • Safranal abrogates the oligomerization of ASC protein. • Safranal inhibits ATP and MSU induced NLRP3 inflammasome activation in mice. [ABSTRACT FROM AUTHOR]

• Virtual screening was employed for discovery of NLRP3 inflammsome inhibitors. • Identified new class of NLRP3 inflammsome inhibitors. • IIIM-1268 inhibited IL-1β release with IC 50 of 2.3 µM. • New inhibitors decreased the protein expression level of mature form of IL-1β. • Molecular modeling studies were performed with ER-1β and NLRP3. • ADME properties were calculated and were within the range. The structure-guided virtual screening (VS) has proved to be successful strategy in identification of new scaffolds for biological targets. The overactivity of NLRP3 inflammasome has been implicated in variety of inflammatory diseases including Alzheimer's disease. The up-regulation of estrogen-receptor β (ER-β) activity has been directly linked with inhibition of NLRP3 inflammasome activity. In the present study, we report discovery of new NLRP3 inflammasome inhibitors via ER-β crystal structure (PDB: 5TOA) guided virtual screening of 20,000 compound library. For experimental validation, top 10 ligands were selected based on structure novelty, docking score, prime MMGB/SA binding affinity and interaction pattern analysis. Amongst the tested compounds, three thiazolidin-4-ones IIIM-1268, IIIM-1269 and IIIM-1270 and benzo[ cd ]indol-2-one IIIM-1266 have shown 73, 69, 75 and 77% suppression of IL-1β release in mouse macrophages (J774A.1 cells) at 10 µM. Benzylidene-thiazolidine-2,4-diones IIIM-1268 and IIIM-1270 inhibited IL-1β release with IC 50 of 2.3 and 3.5 µM and also significantly decreased the protein expression level of mature form of IL-1β in western-blot analysis. IIIM-1266 and IIIM-1270 displayed bidentate H-bonding with Arg 346 and Glu 305 residues in the active site of ER-β; and they also strongly occupied the ADP-binding site of NLRP3 protein. The results presented herein, indicate that ER-β guided VS can be successfully used to identify new NLRP3 inflammasome inhibitors, which may have potential in the development of novel anti-Alzheimer agents. [ABSTRACT FROM AUTHOR]

• Potent inhibitors of cholinesterases. • Dual inhibition of acetylcholinesterase and butyrylcholinesterase. • Display potent induction of P-gp. • Mechanism of AChE/BChE inhibition has been established. • Molecular modeling studies were performed with both enzymes. Alkaloids have always been a great source of cholinesterase inhibitors. Numerous studies have shown that inhibiting acetylcholinesterase as well as butyrylcholinetserase is advantageous, and have better chances of success in preclinical/ clinical settings. With the objective to discover dual cholinesterase inhibitors, herein we report synthesis and biological evaluation of indoloquinoline alkaloid cryptolepine (1) and its bromo-derivative 2. Our study has shown that cryptolepine (1) and its 2-bromo-derivative 2 are dual inhibitors of acetylcholinesterase and butyrylcholinesterase, the enzymes which are involved in blocking the process of neurotransmission. Cryptolepine inhibits Electrophorus electricus acetylcholinesterase, recombinant human acetylcholinesterase and equine serum butyrylcholinesterase with IC 50 values of 267, 485 and 699 nM, respectively. The 2-bromo-derivative of cryptolepine also showed inhibition of these enzymes, with IC 50 values of 415, 868 and 770 nM, respectively. The kinetic studies revealed that cryptolepine inhibits human acetylcholinesterase in a non-competitive manner, with k i value of 0.88 µM. Additionally, these alkaloids were also tested against two other important pathological events of Alzheimer's disease viz. stopping the formation of toxic amyloid-β oligomers (via inhibition of BACE-1), and increasing the amyloid-β clearance (via P-gp induction). Cryptolepine displayed potent P-gp induction activity at 100 nM, in P-gp overexpressing adenocarcinoma LS-180 cells and excellent toxicity window in LS-180 as well as in human neuroblastoma SH-SY5Y cell line. The molecular modeling studies with AChE and BChE have shown that both alkaloids were tightly packed inside the active site gorge (site 1) via multiple π-π and cation-π interactions. Both inhibitors have shown interaction with the allosteric "peripheral anionic site" via hydrophobic interactions. The ADME properties including the BBB permeability were computed for these alkaloids, and were found within the acceptable range. [ABSTRACT FROM AUTHOR]