Graphical representation learning-based approach for automatic classification of electroencephalogram signals in depression.

Depression is a major depressive disorder characterized by persistent sadness and a sense of worthlessness, as well as a loss of interest in pleasurable activities, which leads to a variety of physical and emotional problems. It is a worldwide illness that affects millions of people and should be detected at an early stage to prevent negative effects on an individual's life. Electroencephalogram (EEG) is a non-invasive technique for detecting depression that analyses brain signals to determine the current mental state of depressed subjects. In this study, we propose a method for automatic feature extraction to detect depression by first constructing a graph from the dataset where the nodes represent the subjects in the dataset and where the edge weights obtained using the Euclidean distance reflect the relationship between them. The Node2vec algorithmic framework is then used to compute feature representations for nodes in a graph in the form of node embeddings ensuring that similar nodes in the graph remain near in the embedding. These node embeddings act as useful features which can be directly used by classification algorithms to determine whether a subject is depressed thus reducing the effort required for manual handcrafted feature extraction. To combine the features collected from the multiple channels of the EEG data, the method proposes three types of fusion methods: graph-level fusion, feature-level fusion, and decision-level fusion. The proposed method is tested on three publicly available datasets with 3, 20, and 128 channels, respectively, and compared to five state-of-the-art methods. The results show that the proposed method detects depression effectively with a peak accuracy of 0.933 in decision-level fusion, which is the highest among the state-of-the-art methods.

Tailoring a stable and recyclable nanobiocatalyst by immobilization of surfactant treated Burkholderia cepacia lipase on polyaniline nanofibers for biocatalytic application.

Polyaniline nanofibers were synthesized by the oxidative polymerization of aniline. Surfactant treated lipase from Burkholdaria cepacia was immobilized on these polyaniline nanofibers by adsorption. The activity of immobilized preparation was six times higher than that of free lipase with an enhanced dispersion in organic solvents. Five-level-four-factor central composite design was applied for the optimization of immobilization parameters (viz. reaction time, pH, stirring rate and enzyme-support ratio) which were evaluated on the basis of lipase loading and activity. The thermal stability of the lipase in the nanobioconjugate, demonstrated in terms of the half-life at 80 °C was almost sixteen-fold higher than in the free form. The reusability data revealed the utility of the nanoconjugate for seven consecutive cycles with a slow and gradual decline in the activity. However, the nanoconjugate retained almost 30% of their initial activity after seven cycles of reuse revealing its utility of in industrial applications. The nanoconjugate was used in the kinetic resolution of (RS)-1-(7-(3-chloro-2-hydroxypropoxy)benzofuran-2-yl) ethanone, racemic intermediate of an important ß-blocker (Befunolol), with a high conversion rate of 48.2%, 98% ee-value and enantioselectivity (E) of 188, which signify its importance as a nanobiocatalyst.

Tailoring a robust and recyclable nanobiocatalyst by immobilization of Pseudomonas fluorescens lipase on carbon nanofiber and its application in synthesis of enantiopure carboetomidate analogue.

Pseudomonas fluorescens lipase (PFL) was covalently immobilized on carbon nanofiber (CNF) using 1­ethyl­3­[3­dimethylaminopropyl] carbodiimide (EDC)/N­hydroxysuccinimide (NHS). Surface functionalization of carbon nanofiber augments dispersibility as well as efficiency of covalent immobilization. Crucial parameters for immobilization such as pH, enzyme-support ratio, reaction time and mixing rate were optimized using one factor at a time (OFAT) approach. The nanobiocatalyst prepared under optimized conditions demonstrated a ten-fold increase in enzyme activity and the advantage of high thermal stability (up to 85 °C) along with 10 cycles of reusability. Subsequently practical application of the nanobiocatalyst was explored in the kinetic resolution of racemic 1­phenylethanol into (S)­1­phenylethanol [C = 49.1%, eep = 99.5%, ees = 98.5% and E value = 151.4] followed by Mitsunobu reaction with a substituted pyrrole, giving an enantiopure (R)-carboetomidate analogue (yield = 83%).

Facile immobilization of Pseudomonas fluorescens lipase on polyaniline nanofibers (PANFs-PFL): A route to develop robust nanobiocatalyst.

Herein, we demonstrate the immobilization of Pseudomonas fluorescens lipase (PFL) on polyaniline nanofibers (PANFs) via physical adsorption. Polyaniline nanofibers (PANFs) were synthesized by the oxidative polymerization of aniline. The developed robust nanobiocatalyst (PANFs-PFL) exhibited eight times higher activity than free PFL. In addition, immobilization of lipase on PANFs imparted operational stability of the nanobioconjugate. The various reaction parameters for immobilization (viz. reaction time, pH, stirring rate and enzyme-support ratio) were optimized using statistical design in terms of lipase activity and loading. Furthermore, facile separation, enhanced reusability (upto 6 cycles) and thermostability (upto 75 °C) were additional advantages of the nanobioconjugate. The catalytic prowess of nanobioconjugate was examined in the kinetic resolution of (RS)-N-(4-(3-chloro-2-hydroxypropoxy)phenyl)acetamide and (RS)-1-(1-naphthyl) ethanol in comparison to free PFL. PANFs-PFL demonstrated 49.9% and 48.1% conversion for (RS)-N-(4-(3-chloro-2-hydroxypropoxy)phenyl)acetamide and (RS)-1-(1-naphthyl) ethanol, respectively which signified its importance as a nanobiocatalyst.

Exploration of the expeditious potential of Pseudomonas fluorescens lipase in the kinetic resolution of racemic intermediates and its validation through molecular docking.

A profoundly time-efficient chemoenzymatic method for the synthesis of (S)-3-(4-chlorophenoxy)propan-1,2-diol and (S)-1-chloro-3-(2,5-dichlorophenoxy)propan-2-ol, two important pharmaceutical intermediates, was successfully developed using Pseudomonas fluorescens lipase (PFL). Kinetic resolution was successfully achieved using vinyl acetate as acylating agent, toluene/hexane as solvent, and reaction temperature of 30°C giving high enantioselectivity and conversion. Under optimized condition, PFL demonstrated 50.2% conversion, enantiomeric excess of 95.0%, enantioselectivity (E = 153) in an optimum time of 1 hour and 50.3% conversion, enantiomeric excess of 95.2%, enantioselectivity (E = 161) in an optimum time of 3 hours, for the two racemic alcohols, respectively. Docking of the R- and S-enantiomers of the intermediates demonstrated stronger H-bond interaction between the hydroxyl group of the R-enantiomer and the key binding residues of the catalytic site of the lipase, while the S-enantiomer demonstrated lesser interaction. Thus, docking study complemented the experimental outcome that PFL preferentially acylated the R form of the intermediates. The present study demonstrates a cost-effective and expeditious biocatalytic process that can be applied in the enantiopure synthesis of pharmaceutical intermediates and drugs.

Facile fabrication of a recyclable nanobiocatalyst: immobilization of Burkholderia cepacia lipase on carbon nanofibers for the kinetic resolution of a racemic atenolol intermediate.

Immobilization of surfactant treated Burkholderia cepacia lipase on the surface of carbon nanofibers was performed via two different methods: adsorption and covalent attachment. Simple adsorption of lipase on carbon nanofibers turned out to be a poor strategy, exhibiting an immobilization efficiency of 36%, while covalent coupling using 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide (EDC)/N-hydroxysuccinimide (NHS) showed better immobilization efficiency (56%). The nanobioconjugate fabricated using the latter method showed an eleven-fold increase in enzyme activity towards the hydrolysis of p-nitrophenyl palmitate and enhanced dispersion in organic solvents. At 80 °C, the half-life of lipase in the nanobioconjugate was almost 20 fold higher than that of free lipase, demonstrating its thermal stability. The as-prepared nanobioconjugate was reused for nine consecutive reaction cycles achieving 100% yield in the hydrolysis of p-nitrophenol palmitate but losing almost 50% of the initial activity after seven operational cycles. Finally, this heterogeneous nanobioconjugate was more active and enantioselective [C = 47.8, eep = 97.0 and E = 194] than free lipase [C = 35.4, eep = 97.1 and E = 88] towards the kinetic resolution of a racemic intermediate of atenolol yielding the S enantiomer, which signifies its importance as a nanobiocatalyst.

Production of Mycophenolic Acid by Penicillium brevicompactum Using Solid State Fermentation.

Solid-state fermentation using the microfungus Penicillium brevicompactum for the production of mycophenolic acid is reported in this paper. Of the initial substrates tested (whole wheat, cracked wheat, long grain Basmati rice, and short grain Parmal rice), Parmal rice proved to be the best. Under initial conditions, using steamed Parmal rice with 80% (w/w) initial moisture content, a maximum mycophenolic acid concentration of 3.4 g/kg substrate was achieved in 12 days of fermentation at 25 °C. The above substrate was supplemented with the following additional nutrients (g/L packed substrate): glucose 40.0, peptone 54.0, KH2PO4 8.0, MgSO4⋅7H2O 2.0, glycine 7.0, and methionine 1.65 (initial pH 5.0). A small amount of a specified trace element solution was also added. The final mycophenolic acid concentration was increased to nearly 4 g/kg substrate by replacing glucose with molasses. Replacing Parmal rice with rice bran as substrate further improved the mycophenolic acid production to nearly 4.5 g/kg substrate.

Production of mycophenolic acid by Penicillium brevicompactum-A comparison of two methods of optimization.

Production of mycophenolic acid (MPA) by submerged fermentation using the microfungus Penicillium brevicompactum MTCC 8010 is reported here. Screening experiments were used to identify: the suitable media composition; the optimal initial pH; and the optimal incubation temperature to maximize the production of MPA in batch cultures. The initial concentrations of the selected sources of carbon (glucose), nitrogen (peptone) and the precursors (methionine, glycine) were then optimized by: (1) one-at-a-time variation of factors; and (2) a central composite design (CCD) of experiments, in a 12-day batch culture at an initial pH of 5.0, an incubation temperature of 25 °C, and an agitation speed of 200 rpm. The medium optimized using the one-at-a-time variation yielded a peak MPA titer of 1232 ± 90 mg/L. The medium optimized by the CCD method yielded a 40% higher MPA titer of 1737 ± 55 mg/L. The latter value was nearly 9-fold greater than the titer achieved prior to optimization.