Unravelling diversity, drivers, and indicators of soil microbiome of Trillium govanianum, an endangered plant species of the Himalaya.

In an era of global environmental change, conservation of threatened biodiversity and ecosystem restoration are formidable ecological challenges. The forest understory strata and the belowground soil environment including rhizospheric microbial communities, which are crucial for ecosystem functioning and overall forest biodiversity maintenance, have remained understudied. Here, we investigate the soil microbiome of Trillium govanianum - an endangered Himalayan Forest herb, to unravel the underground diversity, drivers, and potential indicators of the microbial community. We collected rhizospheric and bulk soil samples for microbiome and physicochemical analysis at three sites along an elevation gradient (2500-3300 m) in Kashmir Himalaya. Amplicon sequencing of 16 S rRNA and ITS was used to identify the bacterial and fungal soil microorganisms. We found significant differences in the structure and diversity of microbial community (bacterial and fungal) between the rhizosphere and bulk soil along the altitudinal gradient, and noticeable shifts in the nutrient level in dominant microbial phyla associated with T. govanianum. A significant difference between soil physicochemical parameters and increasing altitude suggests that microbial community structure is determined by altitude and soil type. Similarly, the microbial communities showed a significant (P < 0.05) correlation with soil physicochemical variables along the altitudinal gradient. The moisture content in bacterial and total organic carbon in fungal communities showed the most substantial impact on the physiochemical drivers. We also identify potential bacterial and fungal plant growth promoter indicator species in the soil microbiome of T. govanianum. Overall, our findings provide novel research insights that can be pivotal in designing integrated species recovery programs and long-term restoration plans for T. govanianum, with learnings for biodiversity conservation elsewhere.

Microwave assisted fluidized bed drying of bitter gourd: Modelling and optimization of process conditions based on bioactive components.

Bitter gourds were dried under varied drying conditions in a microwave assisted fluidized bed dryer, and the process was optimized using response surface methodology. Microwave power, temperature and air velocity were used as process variables for drying and the process parameters were varied between 360 and 720 W, 40-60 °C and 10-14 m/s, respectively. The responses determined for deciding the optimal criteria were vitamin C, total phenolics, IC50, total chlorophyll content, vitamin A content, rehydration ratio, hardness and total color change of the dried bitter gourd. Statistical analyses were done by using response surface methodology, which showed that independent variables affected the responses to a varied extent. The optimum drying conditions of 550.89 W microwave power, 55.87 °C temperature, and 13.52 m/s air velocity were established for microwave assisted fluidized bed drying to obtain highest desirability for the dried bitter gourd. At optimum conditions, validation experiment was done to ensure the suitability of models. Temperature and drying time plays an important role in the deterioration of bioactive components. Faster and shorter heating led to the greater retention of bioactive components. Taking the aforesaid results into consideration, our study recommended MAFBD as a promising technique with minimum changes in quality attributes of bitter gourd.

Peptide conformational imprints enhanced the catalytic activity of papain for esterification.

Peptide conformational imprints (PCIs) offer a promising perspective to directly generate binding sites for preserving enzymes with high catalytic activity and stability. In this study, we synthesized a new chiral cross-linker cost-effectively for controlling the matrix morphology of PCIs on magnetic particles (PCIMPs) to stabilize their recognition capability. Meanwhile, based on the flank part of the sequences on papain (PAP), three epitope peptides were selected and synthesized. Molecularly imprinted polymers (MIPs) were then fabricated in the presence of the epitope peptide using our new cross-linker on magnetic particles (MPs) to generate PCIMPs. PCIMPs were formed with helical cavities that complement the PAP structure to adsorb specifically at the targeted position of PAP. PCIMPs65-79 were found to have the best binding parameters to the PAP with K d = 0.087 µM and B max = 4.56 µM. Upon esterification of N-Boc-His-OH, proton nuclear magnetic resonance (1H-NMR) was used to monitor the yield of the reaction and evaluate the activity of PAP/PCIMPs. The kinetic parameters of PAP/PCIMPs65-79 were calculated as V max = 3.0 µM s-1, K m = 5 × 10-2 M, k cat = 1.1 × 10-1 s-1, and k cat/K m = 2.2 M-1 s-1. In addition, PAP is bound tightly to PCIMPs to sustain its activity after four consecutive cycles.

Species richness, abundance, distributional pattern and trait composition of butterfly assemblage change along an altitudinal gradient in the Gulmarg region of Jammu & Kashmir, India.

Despite enormous diversity, abundance, and role in ecosystem processes, little is known about how butterflies differ across altitudinal gradients. For this, butterfly communities were investigated along an altitudinal gradient of 2700-3200 m a.s.l, along the Gulmarg region of Jammu & Kashmir, India. We aimed to determine how the altitudinal gradient and environmental factors affect the butterfly diversity and abundance. Our findings indicate that species richness and diversity are mainly affected by the synergism between climate and vegetation. Alpha diversity indices showed that butterfly communities were more diverse at lower elevations and declined significantly with increase in elevation. Overall, butterfly abundance and diversity is stronger at lower elevations and gradually keep dropping towards higher elevations because floristic diversity decreased on which butterflies rely for survival and propagation. A total of 2023 individuals of butterflies were recorded belonging to 40 species, represented by 27 genera and 05 families. Six survey sites (S I- S VI) were assessed for butterfly diversity from 2018 to 2020 in the Gulmarg region of Jammu & Kashmir. Across the survey, Nymphalidae was the most dominant family represented by 16 genera and 23 species, while Papilionidae and Hesperiidae were least dominant represented by 01 genera and 01 species each. Among the six collection sites selected, Site I was most dominant, represented by 16 genera and 21 species, while Site VI was least dominant, represented by 04 genera and 04 species.

Performance of graphene-zinc oxide nanocomposite coated-glassy carbon electrode in the sensitive determination of para-nitrophenol.

Graphene: zinc oxide nanocomposite (GN:ZnO NC) platform was tried for the sensitive determination of para-nitrophenol (p-NP) through the electrochemical method. ZnO nanoparticles (NPs) were synthesized by the modified wet-chemical method where in potassium hydroxide and zinc nitrate were used as precursors and starch as a stabilizing agent. A green and facile approach was applied to synthesize GN:ZnO NC in which glucose was employed as a reductant to reduce graphene-oxide to graphene in the presence of ZnO NPs. The synthesized NC was characterized using scanning and high-resolution transmission electron microscopy, energy dispersive x-ray analysis, X-ray diffraction and Raman spectroscopic techniques to examine the crystal phase, crystallinity, morphology, chemical composition and phase structure. GN:ZnO NC layer deposited over the glassy carbon electrode (GCE) was initially probed for its electrochemical performance using the standard 1 mM K3[Fe(CN)6] model complex. GN:ZnO NC modified GCE was monitored based on p-NP concentration. An enhanced current response was observed in 0.1 M phosphate buffer of pH 6.8 for the determination of p-NP in a linear working range of 0.09 × 10-6 to 21.80 × 10-6 M with a lower detection limit of 8.8 × 10-9 M employing square wave adsorptive stripping voltammetric technique at a deposition-potential and deposition-time of - 1.0 V and 300 s, respectively. This electrochemical sensor displayed very high specificity for p-NP with no observed interference from some other possible interfering substances such as 2, 4-di-NP, ortho-NP, and meta-NP. The developed strategy was useful for sensitive detection of p-NP quantity in canals/rivers and ground H2O samples with good recoveries.

The modulation of PI3K/Akt pathway by 3ß hydroxylup-12-en-28-oic acid isolated from Thymus linearis induces cell death in HCT-116 cells.

The presence of intricate carbon skeletons in natural compounds enhances their bioactivity spectrum with unique modes of action at several targets in various dreadful diseases like cancer. The present study was designed to purify the molecules from Thymus linearis and elucidate their antiproliferative activity. The compounds were isolated from the active methanolic extract of Thymus linearis through column chromatography and characterized by various spectroscopic techniques. Antiproliferative activity of isolated compounds was evaluated using MTT assay on cancer and normal cell lines. Mechanism of cell death was elucidated using flow cytometric, microscopic, and Western blot analysis. Four compounds, Sitosterol, Chrysin, 3ß-hydroxylup-12-en-28-oic acid (3BH), and ß-Sitosterol glycoside, were isolated. Among these, 3BH was most potent antiproliferative agent across all cell lines under study, HCT-116 being the most affected one. 3BH was demonstrated to downregulate PI3Ksubunits (p110α and p85α), downstream pAktSer473 and prompted G1 phase cell cycle arrest. The cell cycle CDK inhibitor p27 and p21 were upregulated with simultaneous downregulation of cyclin D1 and cyclin E in HCT-116 cells. This was accompanied by apoptosis, as depicted by decrease in Bcl-2/Bax ratio, with increase in active caspases-3 and caspase-9, cleavage of PARP-1, the generation of reactive oxygen species (ROS), and the loss of mitochondrial membrane potential. The findings established that 3BH induced cell death in HCT-116 cells by modulating PI3K/Akt signaling axis, impeding cell cycle, and instigating apoptosis.

Potential Efficacy of Chitosan-Poly (Lactide-Co-Glycolide)-Encapsulated Trivalent Immersion Vaccine in Olive Flounder (Paralichthys olivaceus) Against Viral Hemorrhagic Septicemia Virus, Streptococcus parauberis Serotype I, and Miamiensis avidus (Scuticociliate).

Olive flounder (Paralichthys olivaceus) is the most valuable aquaculture species in Korea, corresponding to ~60% of its total production. However, infectious diseases often break out among farmed flounders, causing high mortality and substantial economic losses. Although some deleterious pathogens, such as Vibrio spp. and Streptococcus iniae, have been eradicated or contained over the years through vaccination and proper health management, the current disease status of Korean flounder shows that the viral hemorrhagic septicemia virus (VHSV), Streptococcus parauberis, and Miamiensis avidus are causing serious disease problem in recent years. Furthermore, these three pathogens have differing optimal temperature and can attack young fingerlings and mature fish throughout the year-round culture cycle. In this context, we developed a chitosan-poly(lactide-co-glycolide) (PLGA)-encapsulated trivalent vaccine containing formalin-killed VHSV, S. parauberis serotype-I, and M. avidus and administered it to olive flounder fingerlings by immersion route using a prime-boost strategy. At 35 days post-initial vaccination, three separate challenge experiments were conducted via intraperitoneal injection with the three targeted pathogens at their respective optimal temperature. The relative percentages of survival were 66.63%, 53.3%, and 66.75% in the group immunized against VHSV, S. parauberis serotype-I, and M. avidus, respectively, compared to the non-vaccinated challenge (NVC) control group. The immunized fish also demonstrated significantly (p < 0.05) higher specific antibody titers in serum and higher transcript levels of Ig genes in the mucosal and systemic tissues than those of NVC control fish. Furthermore, the study showed significant (p < 0.05) upregulation of various immune genes in the vaccinated fish, suggesting induction of strong protective immune response, ultimately leading to improved survival against the three pathogens. Thus, the formulated mucosal vaccine can be an effective prophylactic measure against VHS, streptococcosis, and scuticociliatosis diseases in olive flounder.

Postvaccination SARS-COV-2 among Health Care Workers in New Jersey: A Genomic Epidemiological Study.

Emergence of SARS-CoV-2 with high transmission and immune evasion potential, the so-called variants of concern (VOC), is a major concern. We describe the early genomic epidemiology of SARS-CoV-2 recovered from vaccinated health care professionals (HCP). Our postvaccination COVID-19 symptoms-based surveillance program among HCPs in a 17-hospital network identified all vaccinated HCPs who tested positive for COVID-19 after routine screening or after self-reporting. From 1 January 2021 to 30 April 2021, 23,687 HCPs received either mRNA-1273 or BNT162b2 mRNA vaccine. All available postvaccination SARS-CoV-2 samples and a random collection from nonvaccinated patients during the similar time frame were subjected to VOC screening and whole-genome sequencing (WGS). Sixty-two percent (23,697/37,500) of HCPs received at least one vaccine dose, with 60% (22,458) fully vaccinated. We detected 138 (0.58%, 138/23,697) COVID-19 cases, 105 among partially vaccinated and 33 (0.15%, 33/22,458) among fully vaccinated. Five partially vaccinated required hospitalization, four with supplemental oxygen. VOC screening from 16 fully vaccinated HCPs identified 6 (38%) harboring N501Y and 1 (6%) with E484K polymorphisms; percentage of concurrent nonvaccinated samples was 37% (523/1,404) and 20% (284/1,394), respectively. There was an upward trend from January to April for E484K/Q (3% to 26%) and N501Y (1% to 49%). WGS analysis from vaccinated and nonvaccinated individuals indicated highly congruent phylogenies. We did not detect an increased frequency of any receptor-binding domain (RBD)/N-terminal domain (NTD) polymorphism between groups (P > 0.05). Our results support robust protection by vaccination, particularly among recipients of both doses. Despite VOCs accounting for over 40% of SARS-CoV-2 from fully vaccinated individuals, the genomic diversity appears to proportionally represent VOCs among nonvaccinated populations. IMPORTANCE A number of highly effective vaccines have been developed and deployed to combat the COVID-19 pandemic. The emergence and epidemiological dominance of SARS-CoV-2 mutants with high transmission potential and immune evasion properties, the so-called variants of concern (VOC), continue to be a major concern. Whether these VOCs alter the efficacy of the administered vaccines is of great concern and a critical question to study. We describe the initial genomic epidemiology of SARS-CoV-2 recovered from partial/fully vaccinated health care professionals and probe specifically for VOC enrichment. Our findings support the high level of protection provided by full vaccination despite a steep increase in the prevalence of polymorphisms associated with increased transmission potential (N501Y) and immune evasion (E484K) in the nonvaccinated population. Thus, we do not find evidence of VOC enrichment among vaccinated groups. Overall, the genomic diversity of SARS-CoV-2 recovered postvaccination appears to proportionally represent the observed viral diversity within the community.

Molecular Docking and Simulation Studies of Antidiabetic Agents Devised from Hypoglycemic Polypeptide-P of Momordica charantia.

Diabetes mellitus termed as metabolic disorder is a collection of interlinked diseases and mainly body's inability to manage glucose level which leads to cardiovascular diseases, renal failure, neurological disorders, and many others. The drugs contemporarily used for diabetes have many inevitable side effects, and many of them have become less responsive to this multifactorial disorder. Momordica charantia commonly known as bitter gourd has many bioactive compounds with antidiabetic properties. The current study was designed to use computational methods to discover the best antidiabetic peptides devised from hypoglycemic polypeptide-P of M. charantia. The binding affinity and interaction patterns of peptides were evaluated against four receptor proteins (i.e., as agonists of insulin receptor and inhibitors of sodium-glucose cotransporter 1, dipeptidyl peptidase-IV, and glucose transporter 2) using molecular docking approach. A total of thirty-seven peptides were docked against these receptors. Out of which, top five peptides against each receptor were shortlisted based on their S-scores and binding affinities. Finally, the eight best ligands (i.e., LIVA, TSEP, EKAI, LKHA, EALF, VAEK, DFGAS, and EPGGGG) were selected as these ligands strictly followed Lipinski's rule of five and exhibited good ADMET profiling. One peptide EPGGGG showed activity towards insulin and SGLT1 receptor proteins. The top complex for both these targets was subjected to 50 ns of molecular dynamics simulations and MM-GBSA binding energy test that concluded both complexes as highly stable, and the intermolecular interactions were dominated by van der Waals and electrostatic energies. Overall, the selected ligands strongly fulfilled the drug-like evaluation criterion and proved to have good antidiabetic properties.

In vivo hepatoprotective and in vitro antimicrobial potential of Ceasalpinia bonduc (Linn): Pharmacological correlation with identified phytochemicals.

The in vivo hepatoprotective potential of methanolic extract of Ceasalpinia bonduc (CBLM) has been explored against carbon tetrachloride (CCl4) induced acute liver injury in rats. Treatment of plant extract on CCl4 intoxicated liver significantly reduced the hepatoxicity, along with serum enzymes GPT and GOT. To explore the chemical constituents from CBLM extract, it was fractionated into non-polar to moderately polar fractions (CBLM-H, CBLM-HEt, CBLM-Et, CBLM-EtM, CBLM-M) and subjected to GC/GC-MS analysis. Altogether twenty seven (~71%) phytochemicals were identified from different fractions by using Electronic Mass Spectral Library GC-MS (NIST 20). Out of which twenty one are first time reported from Ceasalpinia bonduc, fourteen from genus Caesalpinia and ten from family Fabaceae. The identified phytochemicals 2-ethyl-2-hydroxy-1,3-dimethylcyclopentanecarboxylic acid, ethyl ester (21) and 1,3,5-triazine-2,4-diamine,6-hydroxy-N,N-dicyclohexyl (23) are first time identified as plant metabolites. To explore the antimicrobial potential four strains of Gram-positive and eight strains of Gram-negative bacteria were used along with pure cultures of five saprophytic fungus (molds) and two strains of yeast were utilized. CBLM-H and CBLM-HEt were exhibited praiseworthy antimicrobial potential. CBLM-H showed complete growth inhibition of P. mirabilis and V. cholerae at the concentration of 0.1g/mL while CBLM-HEt at 0.05g/mL halted the growth of S. aureus.

Enhancement of euryhaline Asterarcys quadricellulare biomass production for improving biogas generation through anaerobic co-digestion with carbon rich substrate.

The microalga was isolated from Muktsar, the southwestern zone of Indian Punjab and identified as Asterarcys quadricellulare BGLR5 (MF661929) by 18S rRNA sequence analysis. The optimization of various cultural factors by the Plackett-Burman and central composite (CCD) designs helped in discerning the significant cultural factors for the increased production of biomass and other functional components (chlorophyll, carbohydrate, lipid and protein). The optimal cultural conditions as per the model were pH 9.9, 81 µmol m-2 s-1 light intensity, 22 °C temperature, growth period of 25 days, NaNO3 12 mM, 15 mM NH4Cl, and 7 mM K2HPO4. In comparison to the basal condition biomass (0.886 g L-1), a 0.42-fold increase in biomass yield was attained. Further, the highest yield of biogas (P: 361.81 mL g-1 VS) with enhanced biogas production rate (R m: 8.19 mL g-1 day-1) was achieved in co-digesting paddy straw with Asterarcys quadricellulare biomass in 1:1 ratio compared to their digestion individually. Further, the co-digestion resulted in the positive synergistic effect which increased the observed biogas yield compared to the estimated yield by 11-58% depending upon the amount of algal biomass and paddy straw used. Hence, the present study signifies that the biomass of Asterarcys quadricellulare BGLR5 can be utilized as a co-substrate with paddy straw to enhance the biogas yield. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02792-x.

Biofabricated platinum nanoparticles: therapeutic evaluation as a potential nanodrug against breast cancer cells and drug-resistant bacteria.

Use of plant extracts for the synthesis of various metal nanoparticles has gained much importance recently because it is a simple, less hazardous, conservative and cost-effective method. In this research work, platinum nanoparticles were synthesized by treating platinum ions with the leaf extract of Psidium guajava and their structural properties were studied using various characterization techniques. The formation of platinum nanoparticles was confirmed by the disappearance of the absorbance peak at 261 nm in UV-visible spectra. The results of gas chromatography-mass spectrometry (GC-MS) and Fourier transform infrared spectroscopy (FT-IR) analysis showed functional moieties responsible for bio-reduction of metal ions and stabilization of platinum nanoparticles. The use of dynamic light scattering (DLS) imaging techniques confirmed the formation of stable monodispersed platinum nanoparticles showing a zeta potential of -23.4 mV. The morphological examination using high resolution transmission electron microscopy (HR-TEM) and Scanning electron microscopy (SEM) confirmed the formation of spherical platinum nanoparticles with an average diameter of 113.2 nm. X-ray powder diffraction (XRD) techniques showed the crystalline nature of biosynthesized platinum nanoparticles with a face-centered cubic structure. The results of energy-dispersive X-ray spectroscopy (EDAX) showed 100% platinum content by weight confirming the purity of the sample. The cytotoxic effect of biosynthesized platinum nanoparticles assessed in a breast cancer (MCF-7) cell-line by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, revealed an IC50 of 167.2 µg ml-1. The results of a wound healing assay showed that treatment with platinum nanoparticles induced an anti-migratory effect on MCF-7 cells. In the cell cycle phase distribution, treatment with platinum nanoparticles inhibited cell proliferation as determined by flow cytometry with PI staining. Significant cell cycle arrest was detected at the G0/G1 phase with a notable decrease in the distribution of cells in the S and G2/M phases. The anti-bacterial activity of bio-synthesized platinum nanoparticles was evaluated against four pathogenic bacteria i.e. B. cereus (Gram positive), P. aeruginosa (Gram negative), K. pneumonia (Gram negative) and E. coli (Gram negative). The biosynthesized platinum nanoparticles were found to show dose-dependent inhibition against pathogenic bacteria with a significant effect on Gram-negative bacteria compared to Gram-positive bacteria. This synergistic blend of green and simplistic synthesis coupled with anti-proliferative and anti-bacterial properties makes these biogenic nanoparticles suitable in nanomedicine.

Surface functionalization: an efficient alternative for promoting the catalytic activity of closed shell gold clusters.

Surface functionalization through adsorption of ligands or non-metal atoms is considered to be an interesting and viable approach for tuning the physicochemical properties of gold clusters. Highly stable and magic numbered electronic configurations of thiolate protected gold clusters such as Au25(SR)18, Au38(SR)24etc. with intriguing properties are the direct manifestation of the rich chemistry of the Au-S interface. The present investigation discerns the CO oxidation activity of structurally well characterized sulphur functionalized gold cluster anions AumS4-, m = 6-10. To establish an in-depth understanding, their activities are analyzed and compared with the corresponding pristine gold clusters. It is seen that sulphur functionalization irrespective of a closed or open shell nature leads to a significant decrease in the O2 adsorption energies on the anionic gold clusters. However, in sharp contrast to O2 adsorption, surface functionalization gives rise to multifarious catalytic behavior in AumS4- clusters with catalytic activity ranging from low (for Au6S4-, Au8S4-) to moderate (for Au9S4-, Au10S4-) to very high (for Au7S4-) for CO oxidation. It is interesting to note that the closed shell Au7S4- and Au9S4- clusters with poor O2 adsorption show remarkably low activation barriers and enhanced catalytic activity as compared to the open shell AumS4- clusters with an odd number of electrons. In particular, in the case of Au7S4- the lowest activation energy barriers of 0.01 and 0.21 eV are obtained, making the CO oxidation reaction facile. Moreover, ab initio molecular dynamics are performed to confirm the enhanced catalytic behaviour of Au7S4- and its dynamical stability during the desorption of CO2 molecule from its surface.

Investigation of electronic, magnetic, elastic, mechanical, thermodynamic, and thermoelectronic properties of Mn2PtV Heusler alloy: ab initio study.

In this paper, we report electronic, magnetic, mechanical thermodynamic, and thermoelectric properties of Mn2PtV using density functional theory. Generalized gradient approximation (GGA) and GGA + U, where U is Hubbard correlation, have been set forth to examine the material for various properties. The material was found to have cubic Fm-3m (225) as the stable ground state. The investigated electronic results within GGA and GGA + U both present metallic nature for the compound. The calculated magnetic moment of 4.87 µB was found for the compound. From mechanical investigation, the material was found to be highly elastic anisotropic, hard, and ductile. The thermodynamic parameters like bulk modulus (B), specific heat at constant volume (Cv), Grüneisen parameter (γ), and Debye temperature (θD) have been predicted with temperature and pressure variation, using quasi-harmonic Debye model. From thermoelectric investigation, the calculated value of Seebeck coefficient was found negative in the entire temperature for both spins, suggesting electrons as charge carriers. The total electronic thermal conductivity was found to have increasing nature with temperature. Power factor (PF), which decides the thermoelectric potential of a material, was found to have a pleasant value under high temperature. The calculated value of PF was found to be 0.75 × 1012 WK-2 m-1 s-1 at 1000 K; hence, the material can find its possible application in waste heat management.

Cutoff Values of Acoustic Radiation Force Impulse Two-Location Measurements in Different Etiologies of Liver Fibrosis.

BACKGROUND: Acoustic radiation force impulse (ARFI) imaging is a popular modality to measure liver fibrosis. ARFI selects optimal locations for measurement under imaging guiding. However, there are concerns on study locations and observers bias. To decrease the variations, ARFI at two locations was measured with standardized protocol. This study attempted to establish its cutoff values according to Metavir fibrosis score in different etiologies. METHODS: A consecutive series of patients who received liver histology study were prospectively enrolled. All cases had hemogram, liver biochemistry, viral markers, and ARFI two-location measurements within 4 weeks of histology study. A standardized protocol was performed by single technologist. We excluded patients with alanine aminotransferase >5x upper limit normal. RESULTS: Five hundred and ten patients that included 153 seronegative for both HBsAg and anti-HCV Non-B non-C (NBNC), 33 autoimmune liver diseases (AILD), 261 chronic hepatitis B (CHB), and 63 chronic hepatitis C (CHC) were enrolled. About 83% of NBNC patients had fat cell >5%. For diagnosis of liver cirrhosis, the area under receiver operating characteristic curve of NBNC, AILD, CHB, and CHC groups was 0.937, 0.929, 0.784, and 0.937; the cutoff values for mean ARFI were 1.788, 2.095, 1.455, and 1.710 m/s, respectively. The sensitivity and specificity are both over 0.818 for patients with nonalcoholic fatty liver diseases, CHC, and AILD, but the corresponding data are only 0.727-0.756 in CHB. The Fibrosis-4 Score is as good as ARFI on fibrosis assessment in NBNC. CONCLUSION: The performance of ARFI two-location measurement is excellent in NBNC, AILD, and CHC, but is only satisfactory in CHB.

Rottlerin is a pan phosphodiesterase inhibitor and can induce neurodifferentiation in IMR-32 human neuroblastoma cells.

Phosphodiesterases are promising targets for pharmacological intervention against various diseases. There are already inhibitors of PDE3, PDE4 and PDE5 as approved drugs. However there is an unmet need to discover new chemical scaffolds as PDE inhibitors. The main drawback of most of PDE inhibitors is their non specificity; owing to their structural resemblance to cAMP or cGMP. Natural product compounds offer high structural diversity hence may provide new PDE inhibitors. We decided to screen our institutional natural product compound library of nearly 900 molecules for PDE5 inhibition and explore the selectivity against PDE1-11 and cytotoxicity of the hit molecule/s. Rottlerin was identified as a PDE5 inhibitor. It was found to inhibit other PDEs with varying specificities. Structure activity relationship data and molecular dynamics studies showed that Tyr612, Asp764, Gln817 and Phe820 in the binding pocket of PDE5 play an important role in the activity of rottlerin. As a pan PDE inhibitor, rottlerin was also found to activate the AMPK pathway and induce neurodifferentiation in IMR-32 cells, with the effect more efficient in samples co-treated with cAMP activator Forskolin. Rottlerin at higher concentrations was shown to induce autophagy, apoptosis and G2/S cell cycle arrest in IMR-32 cells.

Probing the antibacterial and anticancer potential of tryptamine based mixed ligand Schiff base Ruthenium(III) complexes.

Development of new chemotherapeutic agents to treat microbial infections and recurrent cancers is of pivotal importance. Metal based drugs particularly ruthenium complexes have the uniqueness and desired properties that make them suitable candidates for the search of potential chemotherapeutic agents. In this study, two mixed ligand Ru(III) complexes [Ru(Cl)2(SB)(Phen] (RC-1) and [Ru(Cl)2(SB)(Bipy)] (RC-2) were synthesised and characterized by elemental analysis, IR, UV-Vis, 1H, 13C NMR spectroscopic techniques and their molecular structure was confirmed by X-ray crystallography. Antibacterial activity evaluation against two Gram-positive (S. pneumonia and E. faecalis) and four Gram-negative strains (P. aurogenosa, K. pneumoniae, S. enterica, and E. coli) revealed their moderate antibacterial activity with MIC value of ≥250 µg/mL. Anticancer activity evaluation against a non-small lung cancer cell line (H1299) revealed the tremendous anticancer activity of these complexes which was further validated by DNA binding and docking results. DNA binding profile of the complexes studied by UV-Visible and fluorescence spectroscopy showed an intercalative binding mode with CT-DNA and an intrinsic binding constant in the range of 3.481-1.015× 105 M-1. Both the complexes were also found to exert weak toxicity to human erythrocytes by haemolytic assay compared to cisplatin. Potential of these complexes as anticancer agents will be further delineated by in vivo studies.

Investigation on the electronic structure, optical, elastic, mechanical, thermodynamic and thermoelectric properties of wide band gap semiconductor double perovskite Ba2InTaO6.

In the present paper, double perovskite Ba2InTaO6 was investigated in terms of its structural, electronic, optical, elastic, mechanical, thermodynamic and thermoelectric properties using density-functional theory (DFT). The generalized gradient approximation (GGA) in the scheme of Perdew, Burke and Ernzerhof (PBE) and the modified Becke-Johnson (mBJ) potential were employed for the exchange-correlation potential. The computed lattice constant was found to be in agreement with the available experimental and theoretical results. The electronic profile shows a semiconducting nature. Further analysis of the complex dielectric constant ε(ω), refractive index n(ω), reflectivity R(ω), absorption coefficient α(ω), optical conductivity (ω) and energy loss function were also reported with the incident photon energy. The elastic constants were also calculated and used to determine mechanical properties like Young's modulus (Y), the shear modulus (G), Poisson's ratio (ν) and the anisotropic factor (A). The electrical conductivity (σ/τ) and Seebeck coefficient (S) also demonstrated the semiconducting nature of the compound with electrons as the majority carriers. The value of the power factor was calculated to be 1.20 × 1012 W K-2 m-1 s-1 at 1000 K. From thermodynamic investigations, the heat capacity and Grüneisen parameter were also predicted.

Modulation of dietary folate with age confers selective hepatocellular epigenetic imprints through DNA methylation.

The present study has been designed to determine the effect of folate modulation (deficiency/supplementation) with aging on the promoter methylation of tumor suppressor and proto-oncogenes to understand the underlying mechanism of epigenetic alterations. Folate deficiency was induced for 3 and 5 months in weanling, young and adult groups, and after 3 months of folate deficiency, they were repleted with physiological folate (2 mg/kg diet) and folate oversupplementation (8 mg/kg diet) for another 2 months. The methylation facet in the present study revealed that the combined effect of folate deficiency and aging decreased the methylation index. Folate deficiency with age resulted in the up-regulation of proto-oncogenes (C-MYC and C-JUN) and cell cycle regulator gene Cyclin E as a result of promoter hypomethylation. However, in case of tumor suppressor genes (p53, p15ink4b and p16ink4a), the expression levels were found to be decreased at transcriptional level due to promoter hypermethylation. Upon repletion with physiological folate and folate oversupplementation, we found down-regulation of proto-oncogenes and up-regulation of tumor suppressor genes as a result of promoter hypermethylation and hypomethylation, respectively. Deregulation of these important genes due to folate deficiency may contribute toward the pathogenesis at cellular level.

Ethnomycological and Nutritional Analyses of Some Wild Edible Mushrooms from Western Himalayas, Azad Jammu and Kashmir (Pakistan).

Mushrooms have had a long association with humankind and have great biological and economic effects. This study aimed to record ethnomycological and nutritional analysis of some edible mushrooms from the Western Himalayas (Neelum Valley), Azad Jammu and Kashmir, Pakistan. Mushrooms from different taxonomical and ecological groups were collected and properly identified with the help of the available literature: Morchella esculenta, M. crassipes, M. elata, M. conica, Pleurotus ostreatus, Lycoperdon gemmatum, Helvella crispa, Tricholoma megnivelare, Gyrometra esculenta, Agaricus campestris, Hydnum imbricatum, and Sparassis crispa. The local communities are familiar with the morphological features, habitats, and qualities of these mushrooms. Ethnomycological data were collected through the use of a questionnaire; we found that these species have great medicinal value against different ailments. Four species (A. campestris, H. imbricatum, P. ostreatus, and S. crispa) were selected for nutritional analysis (proteins, fats, fiber, and moisture) on the basis of their frequent use in the study area. The largest amounts of protein (1.627 and 1.493 mg/mL) were found in H. imbricatum and S. crispa, respectively. The largest amount of fiber was found in P. ostreatus (14%); S. crispa contains the largest amount of fat (12.7%).