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Delayed–release dimethyl fumarate (DMF), Tecfidera®, is approved globally for treating relapsing-remitting multiple sclerosis. The disposition of DMF was determined in humans after administration of a single oral dose of [14C]DMF, and the total recovery was estimated to be between 58.4% to 75.0%, primarily through expired air.The absorption of [14C]DMF-derived radioactivity was rapid, with Tmax at 1h postdose. Glucose was the predominant circulating metabolite, accounting for ∼60% of the total extractable radioactivity. Cysteine and N-acetylcysteine conjugates of mono- or di-methyl succinate were found to be the major urinary metabolites.In vitro studies showed that [14C]DMF was mainly metabolised to MMF, and fumarase exclusively converted fumaric acid to malic acid and did not catalyse the conversion of fumaric acid esters to malic acid. DMF was observed to bind with human serum albumin through Michael addition to the Cys-34 residue when exposed to human plasma.These findings indicate that DMF undergoes metabolism via hydrolysis, GSH conjugation, and the TCA cycle, leading to the formation of citric acid, CO2, and water. These ubiquitous and well-conserved metabolism pathways minimise the risk of drug-drug interactions and reduce variability related to pharmacogenetics and ethnicity. Delayed–release dimethyl fumarate (DMF), Tecfidera®, is approved globally for treating relapsing-remitting multiple sclerosis. The disposition of DMF was determined in humans after administration of a single oral dose of [14C]DMF, and the total recovery was estimated to be between 58.4% to 75.0%, primarily through expired air. The absorption of [14C]DMF-derived radioactivity was rapid, with Tmax at 1h postdose. Glucose was the predominant circulating metabolite, accounting for ∼60% of the total extractable radioactivity. Cysteine and N-acetylcysteine conjugates of mono- or di-methyl succinate were found to be the major urinary metabolites. In vitro studies showed that [14C]DMF was mainly metabolised to MMF, and fumarase exclusively converted fumaric acid to malic acid and did not catalyse the conversion of fumaric acid esters to malic acid. DMF was observed to bind with human serum albumin through Michael addition to the Cys-34 residue when exposed to human plasma. These findings indicate that DMF undergoes metabolism via hydrolysis, GSH conjugation, and the TCA cycle, leading to the formation of citric acid, CO2, and water. These ubiquitous and well-conserved metabolism pathways minimise the risk of drug-drug interactions and reduce variability related to pharmacogenetics and ethnicity.

The manuscript addresses a robust three-dimensional fuzzy-PID controller (Fuzzy-3D PID) to control frequency of a diverse energy source integrated hybrid power system under various loadings. In ord...

In comparison to the traditional reinforced composites, Friction stir processed composites have emerged to be more promising because of their better properties such as strength, hardness, ductility...

Frequency control is the key factor in a renewable energy-based microgrid system. The inherent dynamics and low inertia of most power generating units of microgrids lead to frequency oscillations i...

The research paper addresses a robust tilt fuzzy cascade (TDF(1+TI)) controller for frequency regulation of an islanded AC microgrid under different uncertainties. The proposed microgrid is modelle...

A safe use of herbicide in the environment can be assessed by it’s adsorption – desorption behavior in soil. In the present work laboratory studies were performed to examine adsorption-desorption b...

The present research article has proposed a robust type-2 fuzzy PID (T2-FPID) controller to obtain automatic generation control (AGC) of a diverse energy source-based multiarea power system under v...

The present manuscript highlights on the frequency regulation of an islanded AC micro-grid under different uncertainties. The advancement in battery-operated vehicles (electric vehicles) keeps envi...

The article contributes a research work on optimal designing of a Fractional Order-Multistage PD/(1 + PI) controller (FO-Multistage) for controlling the frequency of an islanded AC Microgrid under ...

In this paper, an experimental analysis on modified and conventional dual-purpose solar collector (DPSC) using water/air as working fluid. In the conventional DPSC (Type 1), flat absorber plate, co...

In the present study, thermal analysis of two heat exchangers, namely a shell and wire coil-inserted helical coil tube heat exchanger and a shell and without wire coil-inserted helical coil tube he...

The herpetofauna of Nepal have been historically understudied, and although previous studies have reported on bioinventory surveys of the Kathmandu Valley, few have surveyed widely during the peak ...

Majority of studies has been reported in literature in recent years on performance of shell and helical coil tube heat exchanger. The present work attempts to design and analyze experimentally hot ...

Solar energy is the best among all renewable energy sources owing to its low effective cost and eco-friendly character. In this study, the header and riser pipe design is studied using an a...

A series of experiments were carried out using conventional solar still, modified solar stills with stone chips (MSS1), sand stones (MSS2), and calcium oxide (MSS3) for the period of May 2016–Apr 2...

The current research presents a case study of optimal allocation of water for irrigation and power generation at Hirakud reservoir with the application of meta-heuristic algorithm. Hirakud is a mul...

Pr3+ and Ti4+ doped BiFeO3; Bi1-xPrxFe0.80Ti0.20O3 (x = 0.05, 0.10 and 0.15) ceramics were prepared by two stage solid state sintering method. The X-ray diffraction shows large structural distortio...

The present study investigates the prevailing cropping pattern, adopted by the farmers of the study area under consideration. It aims at improving the net benefits from the farming activities with ...

The current work designed to fabricate and evaluate self-nanoemulsfying oil formulations (SNEOFs) of Efavirenz (Efz) a BCS class II drug with the objective of increasing its solubility as well as i...

A study was undertaken to investigate the remedial effect of some soil amendments (farmyard manure (FYM), press mud compost (PMC), cereal straw (CS) at 5 t ha−1 and fresh cow dung slurry (FCD) @ 0.5 t ha−1) on dissipation kinetics of imidacloprid and sulfosulfuron under laboratory conditions. Incorporation of CS or FCD was found to be most effective in degrading both the pesticides at faster rates. Dissipation of both the pesticides could be well accounted by two component (1 + 1) first order kinetics. The computed values of parameters revealed that use of organic amendments increased the dissipated fraction of imidacloprid and sulfosulfuron. Incorporation of CS or FCD in soil maintained relatively higher dissipation rate constants for both faster and slower dissipation processes of pesticides in comparison to control. Hence, eco-friendly practices of CS or FCD incorporation as soil amendment in soil can play a vital role in preventing soil and water pollution.

The main motto behind the performance assessment of an irrigation system is to utilize the available water resources in an efficient and effective manner. In recent times there has been a growing c...

Vikas Kumar,1 Prakash Chandra Bhatt,2 Mahfoozur Rahman,1 Gaurav Kaithwas,3 Hani Choudhry,4,5 Fahad A Al-Abbasi,4 Firoz Anwar,4 Amita Verma6 1Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, Uttar Pradesh, India; 2Centre for Advanced Research in Pharmaceutical Sciences, Microbial and Pharmaceutical Biotechnology Laboratory, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India; 3Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (Central University), Vidya Vihar, Rai Bareli Road, Lucknow, India; 4Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; 5Cancer Metabolism and Epigenetic Unit, King Fahd Center for Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia; 6Bio-organic and Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, Uttar Pradesh, India Abstract: Umbelliferone β-D-galactopyranoside (UFG), isolated from plants, exhibits promising inhibitory action on numerous diseases. The present research was initiated to develop a suitable delivery system for UFG with an intention to enhance its therapeutic efficacy against diethyl nitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in Wistar rats. UFG-loaded polymeric nanoparticles prepared by sonication were scrutinized for average size, drug loading capacity, zeta potential, and drug release potency in animals. HCC cell lines HuH-7 and Hep G2 were used for in vitro cytotoxic investigation. Several hepatic, nonhepatic, antioxidant, and anti-inflammatory biochemical parameters were estimated to establish the anticancer potential of UFG nanoformulation. Microscopical and histopathological investigations were also undertaken to substantiate the results of our work. Umbelliferone β-D-galactopyranoside-loaded poly(d,l-lactide-co-glycolide) nanoparticles (UFG-PLGA-NP) with particle size of 187.1 nm and polydispersity index 0.16 were uniform in nature with 82.5% release of the total amount of drug after 48 h. Our study successfully established the development and characterization of UFG-PLGA-NP with noticeable effect against both in vivo and in vitro models. The anticancer potential of UFG-PLGA-NP was brought about by the management of DEN-induced reactive oxygen species generation, mitochondrial dysfunction, proinflammatory cytokines alteration, and induction of apoptosis. Positive zeta potential on the surface of UFG-PLGA-NP would have possibly offered higher hepatic accumulation of UFG, particularly in the electron-dense mitochondria organelles, and this was the take-home message from this study. Our results demonstrated that such polymer-loaded delivery systems of UFG can be a better option and can be further explored to improve the clinical outcomes against hepatic cancer. Keywords: hepatocellular carcinoma, umbelliferone β-D-galactopyranoside nanoparticles, diethyl nitrosamine, cytokines, oxidative stress&nbsp

Long-term storage of carbon dioxide (CO2) and other forms of carbon in non-atmospheric reservoirs is called carbon sequestration. Selective anthropogenic enrichment of the atmospheric carbon pool is causing dire environmental problems, thereby necessitating remediation by mitigation. Algae possess efficient carbon concentrating mechanisms and consequently high photosynthetic rates which make them suitable candidates for biosequestration of CO2. Globally, nearly half of the atmospheric oxygen is generated by algal photosynthesis despite the fact that algae account for less than 1% of photosynthetic biomass. In water bodies, algae are responsible for creating the ‘biological pump’ that transports carbon from the upper sunlit waters to the depth below. A diverse array of photoautotrophs ranging from prokaryotic cyanobacteria to eukaryotic algae such as Chlorophytes, and even protists like euglenoids, contribute to this ‘biological pump’. It operates in a variety of aquatic ecosystems ranging from sma...

Twenty surface (0–15 cm) samples of acidic soils were analyzed for water soluble (WS), exchangeable (EX), lead displaceable (Pb-disp.), acid soluble (AS), manganese (Mn) oxide occluded (MnOX), organically bound (OB), amorphous Fe oxide occluded (AFeOX), crystalline iron (Fe) oxide occluded (CFeOX) and residual (RES) fractions of Mn, and also for extractable Mn in some common soil extractants: (diethylenetriaminepentaacetic acid (DTPA) (pH 7.3), DTPA (pH 5.3), AB-DTPA (pH 7.6), Mehlich-3 (pH 2.0), Modified Olsen, 0.005 M calcium chloride (CaCl2), 1 M magnesium chloride (MgCl2) and ion exchange resins. The WS-Mn fraction showed a significant and positive correlation with Mn extractable in DTPA (pH 5.3) and AB-DTPA (pH 7.6), while both WS-Mn and EX-Mn fractions correlated significantly and positively with Mn concentration and uptake by maize plants grown in these soils. The AB-DTPA (pH 7.6) and DTPA (pH 5.3) appeared suitable to assess the availability of Mn in acidic soils.

Kinetics and adsorption-desorption behavior of a potent nitrification inhibitor, 2-amino 4-chloro 6-methyl pyrimidine (AM), was examined in Mollisol samples of different depths. Adsorption of AM was better accounted by pseudo-second order kinetics. Adsorption and desorption data of AM onto soil samples of different depths conformed to single surface Freundlich isotherm model. The values of ln K varied from −0.1515 (0–15 cm) to 1.5171 (45–60 cm) and of 1/n from 0.9961 (45–60 cm) to 1.3237 (30–45 cm). Computed values of desorption capacity (ln K’) varied from 3.4734 (0–15 cm) to 4.0674 (45–60 cm) while that of 1/n´ from 0.0017 (45–60 cm) to 0.0367 (0–15 cm). Intensity of desorption (1/n´) had significant positive correlation with soil electrical conductance and clay content. The values of desorption index (n´/n) varied from 14.60 (0–15 cm) to 472.33 (30–45 cm) indicating high degree of irreversibility of adsorbed AM and hence poor leaching from these soils.