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The transportation sector is the largest consumer of fossil fuels; making it a major producer of greenhouse gases. Due to declining fossil fuel reserves and increasingly stringent vehicle emission regulations globally, it is essential to shift to alternative energy sources. Economic and eco-friendly fuel-efficient hybrid, electric, and fuel cell vehicles are regarded as one of the best alternative solutions to cope with the government policies and to reduce the rise in global temperature caused by the automotive sector. Technological advancements in fuel cells, batteries, and chargers have further supported the development of electric vehicles. The major challenges of range and charging time in electric vehicles can be countered by range extension technology and developing all-electric hybrid vehicles. In this review, a comprehensive study of different type of vehicles and their architectures are presented. Insights on energy storage devices and converters of electric vehicles currently in use were also provided. Furthermore, various fuel cell advancements and the technical challenges faced during the commercialization of fuel cell vehicles were highlighted., (© 2021 The Chemical Society of Japan & Wiley-VCH GmbH.)

The recalcitrant spread of the COVID-19 pandemic produced by the novel coronavirus SARS-CoV-2 is one of the most destructive occurrences in history. Despite the availability of several effective vaccinations and their widespread use, this line of immunization often faces questions about its long-term efficacy. Since coronaviruses rapidly change, and multiple SARS-CoV-2 variants have emerged around the world. Therefore, finding a new target-based medication became a priority to prevent and control COVID-19 infections. The main protease (Mpro) is a salient enzyme in coronaviruses that plays a vital role in viral replication, making it a fascinating therapeutic target for SARS-CoV-2. We screened 0.2 million natural products against the Mpro of SARS-CoV-2 using the Universal Natural Product Database (UNPD). As well, we studied the role of ionic liquids (ILs) on the structural stabilization of Mpro. Cholinium-based ILs are biocompatible and used for a variety of biomedical applications. Molecular docking was employed for the initial screening of natural products and ILs against Mpro. To predict the drug-likeness features of lead compounds, we calculated the ADMET properties. We performed MD simulations for the selected complexes based on the docking outcomes. Using MM/PBSA approaches, we conclude that compounds NP-Hit2 (-25.6 kcal mol -1 ) and NP-Hit3 (-25.3 kcal mol -1 ) show stronger binding affinity with Mpro. The hotspot residues of Thr25, Leu27, His41, Met49, Cys145, Met165, and Gln189 strongly interacted with the natural compounds. Furthermore, naproxenate, ketoprofenate, and geranate, cholinium-based ILs strongly interact with Mpro and these ILs have antimicrobial properties. Our findings will aid in the development of effective Mpro inhibitors., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We use first principle approaches to study the adsorption and catalytic activation mechanism of CO 2 on ionic liquids (ILs, [C n MIm] + [Cl] - (n = 0-6)) attached to a Au(111) surface. The adsorption of CO 2 at this liquid-solid model interface occurs via either (i) parallel π-stacking mode or (ii) CO 2 oxygen lone pair (lp)···π interaction. These CO 2 physisorption modes, which depend on the CO 2 landing angle at this interface, are identified as an efficient way to activate CO 2 and its further conversion into value-added products. For illustration, we discuss the conversion of CO 2 into formic acid where the ILs@Au(111) decorated interface allows reduction of the activation energy for the CO 2  + H 2 → HCOOH reaction. In sum, our electrode/electrolyte based interface model provides valuable information to design novel heterogeneous catalysts for CO 2 conversion. Indeed, our work establishes that a suitable interface material is enough to activate CO 2 ., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Mast cells are immune cells of myeloid lineage, characterized by the presence of cytoplasmic granules. These cells play a significant role in multiple pathologies, such as urticaria and type 1 hypersensitivity reactions. Mast cells in tissue sections can be demonstrated with metachromatic stains, such as toluidine blue. Metachromatic staining of mast cells is influenced by the type of mast cell, pH of the staining solution and fixative employed. The objective of this study is to identify a simple, consistent, and reproducible toluidine blue staining method to quantify the mast cells in whole slide skin images using automated image analysis. Skin sections from naive mice and atopic dermatitis mice were stained with toluidine blue methods by Churukian-Schenk and Luna. Luna's toluidine blue staining method without the eosin counterstaining provided optimal staining of mast cells with a greater contrast to the background. The Churukian-Schenk toluidine blue method resulted in slight background staining which confounded the accurate detection and quantification of mast cells in mouse skin sections using an automated image analysis algorithm. Using the Luna toluidine blue stain, a 5-fold increase in the total number of mast cells was observed in atopic dermatitis skin samples as compared to naive mice. In summary, a simple, conventional, and reproducible toluidine blue method was identified to quantify the mast cells in mouse skin sections using an automated image analysis algorithm.

Insulin is a principal hormone that is involved in the regulation of glucose levels in the blood. Oral insulin formulation is a recent development in drug delivery systems. Biocompatible choline-based ionic liquids (ILs) show promising antibacterial activity and are useful for oral and transdermal drug delivery applications. Choline and geranate (CAGE) ILs enhance the stability and oral efficacy of insulin delivery. The molecular mechanism behind insulin formulation in the oral form is at issue. In the present work, the molecular-level understanding of CAGE ILs in insulin is scrutinized by employing atomistic molecular dynamics (MD) simulations. To identify the stability of insulin in an IL medium, we have studied a series of concentration (mole fraction 0.05-1.00) of CAGE ILs with an insulin dimer. It can be well evidenced from the experimental reports that in an aqueous medium, there is a refashioning of CAGE nanostructures at 0.50 mole fraction. It is found from our calculations that the first solvation shell of insulin is readily occupied by choline and geranate ions in the presence of water. Moreover, the geranate ions strongly interacted with the water molecules and thereby, eliminating the intermolecular hydrogen bonding (H-bonding) interactions towards the insulin at 0.30-0.50 mole fraction of CAGE ILs. The most desirable 0.30-0.50 mole fraction of CAGE invigorates water-mediated H-bonding interactions with geranate ions, which also enhances the electrostatic behavior around the vicinity of the insulin dimer. These important findings can help in the development of oral insulin drug delivery and related applications.

Bone is the common extra-hepatic site for cancer metastasis. Hepatic cancer is associated with a higher incidence of pathological fracture. However, this important regulatory mechanism remains unexplored. Thus, exosome-mediated cell-cell communication between hepatocellular cancer and bone might be key to osteolytic bone destruction. Huh-7 exosomes were characterized for size and exosome marker expressions (CD63, Alix). Exosome mediated osteoclast differentiation in the RAW 264.7 cells was monitored from day 1 to 6 and multinucleated osteoclast formation and bone resorption activity were analyzed. The osteoclastogenic factor expressions in the exosomes and osteoclast differentiation markers such as tumor necrosis factor receptor 6 (TRAF6), nuclear factor κB (NF-κB), nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), and cathepsin K (CTSK) were analyzed using western blot. Exosomes released by liver cancer cells (Huh-7) promoted osteoclast differentiation in RAW 264.7 cells. Analysis of osteoclastogenic factors in the exosomes showed that exosomes were specifically enriched with tumor necrosis factor α (TNF-α). Huh-7 exosomes promoted osteoclast differentiation by significantly increasing the number of TRAP-positive multi nucleated osteoclasts and resorption pits. Importantly, exosomes upregulated osteoclast markers TRAF6, NF-κB, and CTSK expressions. Further, neutralizing exosomal TNF-α reverted exosome-mediated osteoclast differentiation in RAW 264.7 cells. Collectively, our findings show that cellular communication of exosomal TNF-α from hepatocellular cancer cells (Huh-7) regulates osteoclast differentiation through NF-κB/CTSK/TRAP expressions. Thus, exosomal TNF-α might act as an important therapeutic target to prevent hepatocellular cancer mediated pathological bone disease., (© 2021 Wiley Periodicals LLC.)

Introduction: Medical education in India is experiencing a paradigm shift from traditional curriculum to competency-based medical education (CBME). It de-emphasizes time-based training and promises greater accountability, flexibility, and learner centeredness. Faculty development is integral in the context of CBME. Considering faculty perceptions toward the new CBME and addressing the difficulties will play a vital role in successful implementation., Materials and Methods: A cross-sectional study was carried out among 297 teaching faculty in 91 medical colleges across 20 states all over India between February and July 2020. A structured validated questionnaire on CBME was used to collect the responses through Google forms and was exported and analyzed in Microsoft Excel., Results: More than 80% opined that Faculty members in departments are not adequate for successful CBME implementation. Reflective learning, early clinical exposure, and elective posting were accepted by 60.2%, 70.4%, and 45.5% of the faculty, respectively. Around 81.8% welcomed horizontal integration, whereas only 54.2% favored vertical integration during the Phase I MBBS., Conclusion: Few reforms such as curtailing the duration of foundation course, sensitization of all medical teachers through faculty development programs, better synchronized vertical integration, increasing the strength of faculty in each department, and adequate infrastructure for skills laboratory can be undertaken as per faculty suggestions., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Education and Health Promotion.)

In the last two decades, incredible progress in various medical imaging modalities and sensing techniques have been made, leading to the proliferation of three-dimensional (3D) imagery. Byproduct of such great progress is the production of huge volume of medical images and this big data place a burden on automatic image processing methods for diagnostic assistance processes. Moreover, large amount of medical imaging data needs to be transmitted with no loss of information for the purpose of telemedicine, remote diagnosis etc. In this work, we consider a hybrid lossless compression technique with object-based features for three-dimensional (3D) medical images. Our approach utilizes two phases as follows: first we determine the volume of interest (VOI) for a given 3D medical imagery using selective bounding volume (SBV) method, and second the obtained VOI is encoded using a hybrid lossless algorithm using Lembel-Ziv-Welch Coding (LZW) followed by arithmetic coding (L to A). Experimental results show that our proposed 3D medical image compression method is comparable with other existing standard lossless encoding methods such as Huffman Coding, Run Length Coding, LZW, and Arithmetic Coding and obtains superior results overall., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

A subset of prostate cancer displays a poor clinical outcome. Therefore, identifying this poor prognostic subset within clinically aggressive groups (defined as a Gleason score (GS) ≧8) and developing effective treatments are essential if we are to improve prostate cancer survival. Here, we performed a bioinformatics analysis of a TCGA dataset (GS ≧8) to identify pathways upregulated in a prostate cancer cohort with short survival. When conducting bioinformatics analyses, the definition of factors such as "overexpression" and "shorter survival" is vital, as poor definition may lead to mis-estimations. To eliminate this possibility, we defined an expression cutoff value using an algorithm calculated by a Cox regression model, and the hazard ratio for each gene was set so as to identify genes whose expression levels were associated with shorter survival. Next, genes associated with shorter survival were entered into pathway analysis to identify pathways that were altered in a shorter survival cohort. We identified pathways involving upregulation of GRB2. Overexpression of GRB2 was linked to shorter survival in the TCGA dataset, a finding validated by histological examination of biopsy samples taken from the patients for diagnostic purposes. Thus, GRB2 is a novel biomarker that predicts shorter survival of patients with aggressive prostate cancer (GS ≧8).

Mitochondrial dysfunction contributes to the pathophysiology of acute kidney injury (AKI). Mitophagy selectively degrades damaged mitochondria and thereby regulates cellular homeostasis. RNA-binding proteins (RBPs) regulate RNA processing at multiple levels and thereby control cellular function. In this study, we aimed to understand the role of human antigen R (HuR) in hypoxia-induced mitophagy process in the renal tubular cells. Mitophagy marker expressions (PARKIN, p-PARKIN, PINK1, BNIP3L, BNIP3, LC3) were determined by western blot analysis. Immunofluorescence studies were performed to analyze mitophagosome, mitolysosome, co-localization of p-PARKIN/TOMM20 and BNIP3L/TOMM20. HuR-mediated regulation of PARKIN/BNIP3L expressions was determined by RNA-immunoprecipitation analysis and RNA stability experiments. Hypoxia induced mitochondrial dysfunction by increased ROS, decline in membrane potential and activated mitophagy through up-regulated PARKIN, PINK1, BNIP3 and BNIP3L expressions. HuR knockdown studies revealed that HuR regulates hypoxia-induced mitophagosome and mitolysosome formation. HuR was significantly bound to PARKIN and BNIP3L mRNA under hypoxia and thereby up-regulated their expressions through mRNA stability. Altogether, our data highlight the importance of HuR in mitophagy regulation through up-regulating PARKIN/BNIP3L expressions in renal tubular cells., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

This study focused on characterizing the potential mechanism of valvular toxicity caused by TGFβ receptor inhibitors (TGFβRis) using rat valvular interstitial cells (VICs) to evaluate early biological responses to TGFβR inhibition. Three TGFβRis that achieved similar exposures in the rat were assessed. Two dual TGFβRI/-RII inhibitors caused valvulopathy, whereas a selective TGFβRI inhibitor did not, leading to a hypothesis that TGFβ receptor selectivity may influence the potency of valvular toxicity. The dual valvular toxic inhibitors had the most profound effect on altering VIC phenotype including altered morphology, migration, and extracellular matrix production. Reduction of TGFβ expression demonstrated that combined TGFβ2/β3 inhibition by small interfering RNA or neutralizing antibodies caused similar alterations as TGFβRis. Inhibition of TGFβ3 transcription was only associated with the dual TGFβRis, suggesting that TGFβRII inhibition impacts TGFβ3 transcriptional regulation, and that the potency of valvular toxicity may relate to alteration of TGFβ2/β3-mediated processes involved in maintaining proper balance of VIC phenotypes in the heart valve., Competing Interests: All authors are employees of BMS and may own shares of company stocks, but there are no conflicts of interest in regard to the disclosure of data associated with this study., (© 2021 The Author(s).)

Purpose: Periodontitis is an inflammatory disease that results in loss of connective tissue and bone support. Evidence shows a possible relationship between periodontitis and age-related macular degeneration (AMD)., Methods: This population-based cohort study was conducted using data from the National Health Insurance Research Database in Taiwan, with a 13-year follow-up, to investigate the risk of AMD in patients with periodontitis. The periodontitis cohort included patients with newly diagnosed periodontitis between 2000 and 2012. The nonperiodontitis cohort was frequency-matched with the periodontitis cohort by age and sex, with a sample size of 41,661 in each cohort., Results: Patients with periodontitis had an increased risk of developing AMD compared with individuals without periodontitis (5.95 vs. 3.41 per 1,000 person-years, adjusted hazard ratio = 1.58 [95% confidence interval, 1.46-1.70]). The risk of developing AMD remained significant after stratification by age (adjusted hazard ratio = 1.48 [1.34-1.64] for age <65 years and 1.76 [1.57-1.97] for age ≥65 years), sex (adjusted hazard ratio = 1.40 [1.26-1.55] for women and 1.82 [1.63-2.04] for men), and presence of comorbidity (adjusted hazard ratio = 1.52 [1.40-1.66] for with comorbidity and 1.92 [1.63-2.26] for without comorbidity). In addition, patients with periodontitis showed an increased incidence for both nonexudative type AMD (5.43 vs. 3.13 per 1,000 person-years) and exudative type AMD (0.52 vs. 0.28 per 1,000 person-years)., Conclusion: People with periodontitis could be at a greater risk of developing AMD than those without periodontitis. However, we need more evidence to support this association.

Background: Acute kidney injury (AKI) affects a large proportion of the critically ill and is associated with worse patient outcomes. Early identification of AKI can lead to earlier initiation of supportive therapy and better management. In this study, we evaluate the impact of computerized AKI decision support tool integrated with the critical care clinical information system (CCIS) on patient outcomes. Specifically, we hypothesize that integration of AKI guidelines into CCIS will decrease the proportion of patients with Stage 1 AKI deteriorating into higher stages of AKI., Methods: The study was conducted in two intensive care units (ICUs) at University Hospitals Bristol, UK, in a before (control) and after (intervention) format. The intervention consisted of the AKIN guidelines and AKI care bundle which included guidance for medication usage, AKI advisory and dashboard with AKI score. Clinical data and patient outcomes were collected from all patients admitted to the units. AKI stage was calculated using the Acute Kidney Injury Network (AKIN) guidelines. Maximum AKI stage per admission, change in AKI stage and other metrics were calculated for the cohort. Adherence to eGFR-based enoxaparin dosing guidelines was evaluated as a proxy for clinician awareness of AKI., Results: Each phase of the study lasted a year, and a total of 5044 admissions were included for analysis with equal numbers of patients for the control and intervention stages. The proportion of patients worsening from Stage 1 AKI decreased from 42% (control) to 33.5% (intervention), p = 0.002. The proportion of incorrect enoxaparin doses decreased from 1.72% (control) to 0.6% (intervention), p < 0.001. The prevalence of any AKI decreased from 43.1% (control) to 37.5% (intervention), p < 0.05., Conclusions: This observational study demonstrated a significant reduction in AKI progression from Stage 1 and a reduction in overall development of AKI. In addition, a reduction in incorrect enoxaparin dosing was also observed, indicating increased clinical awareness. This study demonstrates that AKI guidelines coupled with a newly designed AKI care bundle integrated into CCIS can impact patient outcomes positively.

Autophagy, an important cellular homeostatic mechanism regulates cell survival under stress and protects against acute kidney injury. However, the role of long noncoding RNA (lncRNA) in autophagy regulation in renal tubular cells (HK-2) is unclear. The study was aimed to understand the importance of lncRNA in hypoxia-induced autophagy in HK-2 cells. LncRNA eosinophil granule ontogeny transcript (EGOT) was identified as autophagy-associated lncRNA under hypoxia. The lncRNA EGOT expression was significantly downregulated in renal tubular cells during hypoxia-induced autophagy. Gain- and loss-of-EGOT functional studies revealed that EGOT overexpression reduced autophagy by downregulation of ATG7, ATG16L1, LC3II expressions and LC 3 puncta while EGOT knockdown reversed the suppression of autophagy. Importantly, RNA-binding protein, (ELAVL1)/Hu antigen R (HuR) binds and stabilizes the EGOT expression under normoxia and ATG7/16L1 expressions under hypoxia. Furthermore, HuR mediated stabilization of ATG7/16L1 expressions under hypoxia causes a decline in EGOT levels and thereby promotes autophagy. Altogether, the study first reveals the functional interplay of lncRNA EGOT and HuR on the posttranscriptional regulation of the ATG7/16L1 expressions. Thus, the HuR/EGOT/ATG7/16L1 axis is crucial for hypoxia-induced autophagy in renal tubular cells., (© 2020 Wiley Periodicals, Inc.)

Periodontitis is a multifactorial inflammatory disease that can cause tooth loss and contribute to systemic inflammation. It is suggested that periodontitis may be associated with the development of glaucoma. Based on data from Taiwan's National Health Insurance Research Database, a retrospective cohort study was conducted to investigate the risk of developing glaucoma in patients with periodontitis. The periodontitis cohort consisted of newly diagnosed adult patients (n = 194,090, minimum age = 20 years) between 2000 and 2012. The comparison group included age-, gender-, and diagnosis date-matched people without periodontitis (n = 194,090, minimum age = 20 years). Incident glaucoma was monitored until the end of 2013. Hazard ratios (HRs) with confidence intervals (CIs) were established based on the Cox proportional hazard models. The risk of developing glaucoma was higher in patients with periodontitis than those without periodontitis (31.2 vs. 23.3 patients per 10,000 person-years, with an adjusted HR of 1.26 [95% CI 1.21-1.32]). A high risk was evident even after stratifying by age (adjusted HRs = 1.34 [1.26-1.44] for ages 20-49, 1.24 [1.13-1.36] for ages ≥ 65, and 1.20 [1.12-1.29] for ages 50-64 years), sex (adjusted HRs = 1.33 [1.24-1.41] and 1.21 [1.14-1.28] for men and women, respectively), presence of comorbidity (adjusted HRs = 1.38 [1.29-1.47] and 1.18 [1.12-1.25] for without and with comorbidity, respectively), and corticosteroid use (adjusted HRs = 1.27 [1.21-1.33] and 1.21 [1.08-1.35] for without and with corticosteroid use, respectively). Specifically, patients with periodontitis exhibited a significantly high risk of primary open-angle glaucoma (adjusted HR = 1.31 [1.21-1.32]) but not for primary closed-angle glaucoma (adjusted HR = 1.05 [0.94-1.17]). People with periodontitis are at a greater risk of glaucoma than individuals without periodontitis. Ocular health should be emphasized for such patients, and the underlying mechanisms need further investigation.

Fucoidan is a unique bioactive and dietary polymer enriched mainly in the cell wall matrix of the brown seaweeds. This present study was intended to reveal the antigenotoxicity effect of fucoidan on 4-nitroquinolin-1-oxide (4-NQO) induced genetics damage and apoptosis in mice bone marrow cells. The 4-NQO caused genetic damages in the form of chromosome/chromatic breakage was estimated by micronuclei assay whereas apoptosis by annexin-V FITC kit and DNA damage by comet assay kit. In addition, oxidative damage in terms of plasma lipid peroxidation (LPO) and 8-OHdG was also estimated. In the experimental regime, six groups with each in five either sex of mice were used. Fucoidan constituted (50,100,200 mg/kg bwt) by orally for 5 days consequently and on 6th day, 4-NQO was administered (7.5 mg/kg bwt) by i.p. The results clearly show that negative control (H 2 O) and fucoidan alone constituted mice were not exhibited significant effect on LPO, genetic damages whereas positive control group (4-NQO 7.5 mg/kg bwt, i.p.) showed significant effect on genetic damage by showing increased level of LPO (6.25 vs 1.3 μM MDA), 8-OHdG (12 vs 4%), micronuclei about six-fold, 5-fold of comet, and 4-fold of apoptosis when compared with negative control, 11.6 ± 2.07, 5.00 ± 1.58, and 4.14 ± 0.65 respectively. Fucoidan pretreatment significantly protected the 4-NQO-induced genetic damage by 77% decreased level of micronuclei and 96% comet at dose of 200 mg/kg bwt over the positive control whereas LPO, 8-OHdG, and apoptosis were restored as equal to negative control. This study found as fucoidan possessing significant antigenotoxicity property by protecting 4-NQO-induced genetic damage in mice bone marrow cells as dose dependent manner suggest as valuable food supplements and medicine for mankind from environmental toxicants.

IRAK4 is an attractive therapeutic target for the treatment of inflammatory conditions. Structure guided optimization of a nicotinamide series of inhibitors has been expanded to explore the IRAK4 front pocket. This has resulted in the identification of compounds such as 12 with improved potency and selectivity. Additionally 12 demonstrated activity in a pharmacokinetics/pharmacodynamics (PK/PD) model. Further optimization efforts led to the identification of the highly kinome selective 21 , which demonstrated a robust PD effect and efficacy in a TLR7 driven model of murine psoriasis., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Calcium carbonate (CaCO 3 ) scale inhibition by Diethylenetriaminepentaacetic acid (DTPA) on copper and aluminium metal surfaces was studied at 60 and 100 °C. The samples were characterized using X-ray diffraction (XRD), Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The results revealed a novel pot like morphology for calcite which was resulted from the transformation of dumbbell morphology. The pot like morphology exposed the possibility of hollow structures for other polymorphs and is resulted from the breaking apart of the dumbbell structures at the middle, followed by fluffing of the separated parts., (© 2020 Published by Elsevier Ltd.)

Novel imidazole-based TGFβR1 inhibitors were identified and optimized for potency, selectivity, and pharmacokinetic and physicochemical characteristics. Herein, we report the discovery, optimization, and evaluation of a potent, selective, and orally bioavailable TGFβR1 inhibitor, 10 (BMS-986260). This compound demonstrated functional activity in multiple TGFβ-dependent cellular assays, excellent kinome selectivity, favorable pharmacokinetic properties, and curative in vivo efficacy in combination with anti-PD-1 antibody in murine colorectal cancer (CRC) models. Since daily dosing of TGFβR1 inhibitors is known to cause class-based cardiovascular (CV) toxicities in preclinical species, a dosing holiday schedule in the anti-PD-1 combination efficacy studies was explored. An intermittent dosing regimen of 3 days on and 4 days off allowed mitigation of CV toxicities in one month dog and rat toxicology studies and also provided similar efficacy as once daily dosing., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Background and Objective: In order to reduce time complexity and to improve the computational efficiency in diagnosing process, automated brain tissue segmentation for magnetic resonance brain images is proposed in this paper., Methods: This method incorporates two processes, the first one is preprocessing and the second one is segmentation of brain tissue using Histogram based Swarm Optimization techniques. The proposed method was investigated with images obtained from twenty volumes and eighteen volumes of T1-Weighted images obtained from Internet Brain Segmentation Repository (IBSR), Alzheimer disease images from Minimum Interval Resonance Imaging in Alzheimer's Disease (MIRIAD) and T2-Weighted real-time images collected from SBC Scan Center Dindigul., Results: The proposed technique was tested with three brain image datasets. Quantitative evaluation was done with Jaccard (JC) and Dice (DC) and also it was compared with existing swarm optimization techniques and other methods like Adaptive Maximum a posteriori probability (AMAP), Biased Maximum a posteriori Probability (BMAP), Maximum a posteriori Probability (MAP), Maximum Likelihood (ML) and Tree structure K-Means (TK-Means)., Conclusion: The performance comparative analysis shows that our proposed method Histogram based Darwinian Particle Swarm Optimization (HDPSO) gives better results than other proposed techniques such as Histogram based Particle Swarm Optimization (HPSO), Histogram based Fractional Order Darwinian Particle Swarm Optimization (HFODPSO) and with existing swarm optimization techniques and other techniques like Adaptive Maximum a posteriori Probability (AMAP), Biased Maximum a posteriori Probability (BMAP), Maximum a posteriori Probability (MAP), Maximum Likelihood (ML) and Tree structure K-Means (TK-Means)., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The Keap1-Nrf2-ARE system serves as a premier defence mechanism to curb oxidative stress, which remains as one of the major causes of ageing and pathogenesis in various diseases. Nrf2 is the principal master regulator of the cellular defence system, and its activation remains the prospective therapeutic approach against chronic diseases. One of the recent strategies is to disrupt Keap1-Nrf2 protein-protein interaction (PPI) that alters the docking of Keap1 with Nrf2 by compounds occupying a position in the Keap1 blocking the interface with Nrf2. In this study, we made an attempt to identify the compounds with anticancer, antioxidant and anti-inflammatory properties to disrupt Keap1a/b-Nrf2 PPI through in silico molecular docking in zebrafish. The phylogenetic analysis of Keap1 proteins revealed the existence of orthologous Keap1-Nrf2-ARE system in lower vertebrates that includes zebrafish. The DGR domains of zebrafish Keap1a and Keap1b were modelled with Modeller 9.19 using Keap1 of Mus musculus (PDB ID:5CGJ) as template. Based on the docking calculations, top hit compounds were identified to disrupt both Keap1a and Keap1b interaction with Nrf2 which include quercetin 3,4'-diglucoside, flavin adenine dinucleotide disodium salt hydrate, salvianolic acid A, tunicamycin and esculin. The LC 50 of esculin in 3 dpf zebrafish larvae is 5 mmol/L, and the qRT-PCR results showed that esculin significantly increased the transcription of Nrf2 target genes-Gstpi, Nqo1, Hmox1a and Prdx1 in 3 dpf zebrafish larvae. These potential hits could serve as safer Nrf2 activators due to their non-covalent disruption of Keap1-Nrf2 PPI and be developed into efficacious preventive/therapeutic agents for various diseases., (© 2019 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Background: Acute kidney injury is common in critically ill patients with detrimental effects on mortality, length of stay and post-discharge outcomes. The Acute Kidney Injury Network developed guidelines based on urine output and serum creatinine to classify patients into stages of acute kidney injury., Methods: In this analysis we utilize the Acute Kidney Injury Network guidelines to evaluate the acute kidney injury stage in patients admitted to general and cardiac intensive care units over a period of 18 months. Acute kidney injury stage was calculated in real time hourly based on the guidelines and using these temporal stage scores calculated for the population; the prevalence and progression of acute kidney injury stage was compared between the two units. We hypothesized that the prevalence and progression of acute kidney injury stage between the two units may be different., Results: More cardiac intensive care unit patients had no acute kidney injury (stage <1) during their intensive care unit stay but more cardiac intensive care unit patients developed acute kidney injury (stage >1), compared to the General Intensive Care Unit. Both at intensive care unit admission and discharge, more General Intensive Care Unit patients had acute kidney injury; however, the number of cardiac intensive care unit patients with acute kidney injury was three times higher at discharge than admission. Acute kidney injury developed in a different pattern in the two intensive care units over five days of intensive care unit stay. In the General Intensive Care Unit, acute kidney injury was most prevalent on second day of intensive care unit stay and in cardiac intensive care unit acute kidney injury was most prevalent on the third day of intensive care unit stay. We observed the biggest increase in new acute kidney injury in the first day of General Intensive Care Unit and second day of the cardiac intensive care unit stay., Conclusions: The study demonstrates the different trends of acute kidney injury pattern in general and cardiac intensive care unit patient populations highlighting the earlier development of acute kidney injury on General Intensive Care Unit and more prevalence of acute kidney injury on discharge from cardiac intensive care unit.

Background/purpose: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease affecting oral health. Evidence shows possible association between T1DM and periodontal diseases (PDs). We conducted a nationwide population-based study in Taiwan, with a 14-year follow-up to investigate the risk of PDs in T1DM patients., Methods: We used data from the National Health Insurance Research Database in Taiwan. The T1DM cohort was identified with newly diagnosed T1DM from 1998 to 2011. The non-T1DM cohort was frequency matched with the T1DM cohort. Participants comprised 4248 patients in the T1DM cohort and 16992 persons in the non-T1DM cohort., Results: The T1DM patients showed an increased risk of PDs compared to non-T1DM individuals [adjusted hazard ratio (aHR) = 1.45]. T1DM patients who visited the emergency room more than twice per year had a higher aHR of 13.0 for developing PDs. The aHR for PDs was 13.2 in the T1DM patients who had been hospitalized more than twice per year., Conclusion: T1DM patients are at higher risk of developing PDs than non-T1DM individuals. Our results further showed that the number of T1DM interventions; that is, annual emergency visits and hospitalizations were associated with increased the risk of developing PDs., (Copyright © 2018. Published by Elsevier B.V.)

Objective: The microenvironment of outer retina is largely regulated by retinal pigment epithelium (RPE) and choroid. Damage to either of these layers lead to the development of age related macular degeneration (AMD). A simplified cell culture model that mimics the RPE/Bruch's membrane (BM) and choroidal layers of the eye is a prerequisite for elucidating the molecular mechanism of disease progression., Results: We have isolated primary retinal pigment epithelial cells (hRPE) and human primary choroidal endothelial cells (hCEC) from donor eyes to construct a bilayer of hCEC/hRPE on transwell inserts. Secretion of VEGF in the insert grown bilayer was significantly higher (22 pg/ml) than hCEC monolayer (3 pg/ml). To mimic the disease condition the model was treated with 100 ng/ml of VEGF, which increased the permeability of bilayer for 20 kDa FITC dextran while addition of bevacizumab, a humanized anti-VEGF drug, reversed the effect. To conclude the transwell insert based human primary hCEC/hRPE bilayer model would be an ideal system for studying the disease mechanisms and the crosstalk between RPE and choroid. This model will also be useful in screening small molecules and performing drug permeability kinetics.

Waterborne infections are responsible for health problems worldwide and their prompt and sensitive detection in recreational and potable water is of great importance. Bacterial identification and enumeration in water samples ensures water is safe for its intended use. Culture-based methods can be time consuming and are usually performed offsite. There is a need to for automated and distributed at-source detectors for water quality monitoring. Herein we demonstrate a microvolume Escherichia coli ( E. coli ) detector based on a screen printed electrode (SPE) bioelectroanalytical system and explore to what extent performance can be improved by coupling it with a filtration device. To confidently benchmark detector performance, we applied a statistical assessment method to target optimal detection of a simulated concentrated sample. Our aim was to arrive at a holistic understanding of device performance and to demonstrate system improvements based on these insights. The best achievable detection time for a simulated 1 CFU mL -1 sample was 4.3 (±0.6) h assuming no loss of performance in the filtration step. The real filtered samples fell short of this, extending detection time to 16-18 h. The loss in performance is likely to arise from stress imposed by the filtration step which inhibited microbial growth rates.

The conventional view of conversion reaction is based on the reversibility, returning to an initial material structure through reverse reaction at each cycle in cycle life, which impedes the complete understanding on a working mechanism upon a progression of cycles in conversion-reaction-based battery electrodes. Herein, a series of tin-doped ferrites (Fe 3- x Sn x O 4 , x = 0-0.36) are prepared and applied to a lithium-ion battery anode. By achieving the ideal reoxidation into SnO 2 , the Fe 2.76 Sn 0.24 O 4 composite anchored on reduced graphene oxide shows a high reversible capacity of 1428 mAh g -1 at 200 mA g -1 after 100 cycles, which is the best performance of Sn-based anode materials so far. Significantly, a newly formed γ-FeOOH phase after 100 cycles is identified from topological features through synchrotron X-ray absorption spectroscopy with electronic and atomic structural information, suggesting the phase transformation from magnetite to lepidocrocite upon cycling. Contrary to the conventional view, our work suggests a variable working mechanism in an iron-based composite with the dynamic phases from iron oxide to iron oxyhydroxide in the battery cycle life, based on the reactivity of metal nanoparticles formed during reaction toward the solid electrolyte interface layer.

This study investigates the heat transfer and the pressure drop of cone helically coiled tube heat exchanger using (Multi wall carbon nano tube) MWCNT/water nanofluids. The MWCNT/water nanofluids at 0.1%, 0.3%, and 0.5% particle volume concentrations were prepared with the addition of surfactant by using the two-step method. The tests were conducted under the turbulent flow in the Dean number range of 2200 < De < 4200. The experiments were conducted with experimental Nusselt number is 28%, 52% and 68% higher than water for the nanofluids volume concentration of 0.1%, 0.3% and 0.5% respectively. It is found that the pressure drop of 0.1%, 0.3% and 0.5% nanofluids are found to be 16%, 30% and 42% respectively higher than water. It is studied that the prepared MWCNT/water nanofluids show good stability even after 45 days of preparation and there is no considerable deposit of nanotubes on the tube inner wall. It is also studied that there is no immediate risk of handling MWCNT and studied that there is no significant erosion of coiled tube inner wall surface even after several test runs. Therefore the MWCNT/water nanofluids are the alternate heat transfer fluids for traditional fluids in the cone helically coiled tube heat exchanger to improve the heat transfer with considerable pressure drop.

Autophagy, a prosurvival mechanism offers a protective role during acute kidney injury. We show novel findings on the functional role of RNA binding protein, HuR during hypoxia-induced autophagy in renal proximal tubular cells-2 (HK-2). HK-2 cells showed upregulated expressions of HuR and autophagy-related proteins such as autophagy related 7 (ATG7), autophagy related 16 like 1 (ATG16L1), and LC3II under hypoxia. Increased autophagosome formation was visualized as LC3 puncta in hypoxic cells. Further, short hairpin-RNA-mediated loss of HuR function in HK-2 cells significantly decreased ATG7 and ATG16L1 protein expressions. Bioinformatics prediction revealed HuR motif binding on the coding region of ATG7 and AU-rich element at 3'UTR ATG16L1 messnger RNA (mRNA). The RNA immunoprecipitation study showed that HuR was predominantly associated with ATG7 and ATG16L1 mRNAs under hypoxia. In addition, HuR enhanced autophagosome formation by regulating LC3II expressions. These results show that HuR regulates ATG7 and ATG16L1 expressions and thereby mediate autophagy in HK-2 cells. Importantly, HuR knockdown cells underwent apoptosis during hypoxia as observed through the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Collectively, these findings show the crucial role of HuR under hypoxia by regulating autophagy and suppressing apoptosis in renal tubular cells., (© 2018 Wiley Periodicals, Inc.)

Neovascularization in retina and choroid involves interplay of many cytokines and growth factors. Vascular endothelial growth factor (VEGF) being a pro-angiogenic molecule has been found to be high in aqueous and vitreous humour of patients with proliferative diabetic retinopathy (PDR). VEGF is also found in the fibroblast and retinal pigment epithelial cells (RPE) of choroidal neovascular (CNV) membranes isolated from patients. Though anti-VEGF agents cause regression of clinically visible new vessels, there is evidence that they increase the occurrence of retinal tractional detachment and other adverse effects in PDR and CNV treatments. Adiponectin (APN) is a cytokine, found to be involved in the pathobiology of PDR. It is unclear whether APN plays a reparative or pathological role in the disease condition. In this study, we explored the effect of APN on tube formation in the primary culture of human umbilical vein macrovascular endothelial cells (HUVEC), human retinal microvascular endothelial cells (hREC) and human choroidal endothelial cells (hCEC). Anti-VEGF agent, bevacizumab (avastin) was used as a control. Full-length pAc-APN transfected in HUVEC, hRECs and hCECs inhibited basal tube formation and migration comparable to bevacizumab (Avastin™). In hRECs, full length pAc-APN reduced VEGF or PDR vitreous mediated migration. In a similar way, rAPN significantly disrupted VEGF and PDR vitreous induced tube formation in HUVEC and hREC. Moreover, rAPN significantly reduced VEGF influenced proliferation and phosphorylation of ERK1/2 in hREC. Altogether, our study suggests that APN may be effective in the treatment of retinal neovascularization., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Fibrosis in ocular tissues causes severe visual deterioration and blindness in patients with glaucoma, cataract, age related macular degeneration (AMD) and diabetic retinopathy (DR). Currently available anti-fibrotic agents exhibit undesirous cytotoxic effects and thus prove ineffective to treat post-surgical fibrosis. Accordingly, there is a need to develop efficient and novel anti-fibrotic agents. Adiponectin (APN), an adipokine from adipocytes is increased in the aqueous and vitreous humor of the patients with micro-angiopathy and chronic inflammation. Furthermore, it is reported to be elevated in the subretinal fluid, vitreous and epiretinal membrane of patients with AMD, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR) respectively. Since APN has anti-angiogenic activity and reduces VEGF levels, we hypothesize that APN might regulate the angio-fibrotic switch and drive the formation of fibrovascular membrane at advanced stages of AMD, PVR and PDR. Intriguingly, APN is shown to inhibit liver, cardiac and pulmonary fibrosis, yet it accelerates renal fibrosis. Therefore, the factors such as tissue and cell type, disease specific pathological milieu and the choice of APN receptor interaction could determine the pro- or anti-fibrotic nature of APN. We speculate that APN could play a profibrotic role in the posterior segment of the eye., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Medial opening wedge high tibial osteotomy (HTO) entails extensive soft tissue release that may lead to substantial perioperative bleeding. Although tranexamic acid (TXA) is a well-established blood-conserving agent in total joint arthroplasty, its potential to reduce blood loss in patients undergoing HTO has not been studied extensively., Questions/purposes: (1) Does TXA reduce total estimated blood loss in HTO? (2) Does TXA use in HTO affect in-hospital endpoints as measured by visual analog scale (VAS) pain scores at rest the day after surgery, wound complications in the immediate postoperative period, blood transfusions, or symptomatic deep vein thrombosis?, Methods: Between January 2015 and May 2017, a single surgeon performed 156 HTOs, all of which were done using the medial opening wedge technique. We began using intravenous TXA for all HTOs in June 2016. This left us with 89 patients who were treated during a time when no TXA was used and 67 patients who were treated when all patients received TXA. Two patients in the control group had simultaneous TKA in the contralateral leg and one patient in each group had missing data so these patients were excluded, leaving 86 (97%) patients in the control group and 66 (98.5%) in the TXA group available for analysis in this retrospective study. There were no demographic differences between the groups in terms of age, sex, body mass index, and baseline hemoglobin values. Total estimated blood loss was the primary outcome variable, which was calculated using total blood volume and decrease in hemoglobin values. Secondary outcome variables included pain VAS at rest the day after surgery, wound complications in the immediate postoperative period, allogeneic blood transfusions, and occurrence of symptomatic thromboembolic manifestations. The decision on when to transfuse was based on predetermined criteria. An orthopaedic surgeon not involved in patient care collected the patient data from electronic medical records and did chart review., Results: The TXA group had less total blood loss (372 ± 36 mL versus 635 ± 53 mL, mean difference 263 mL [95% confidence interval, 248-278]; p < 0.001). Between groups, differences in VAS pain scores at rest the day after surgery favored the TXA group but were small and unlikely to be clinically important. There were two wound complications in the control group (one hematoma and one superficial wound infection) and none in the TXA group. No patients in either group received a blood transfusion, and no symptomatic thromboembolic events were detected in either group., Conclusions: This study demonstrates that the systemic administration of TXA reduces postoperative blood loss in medial opening wedge HTO; however, insofar as no transfusions were administered to patients even before the routine use of TXA in this series, and no clinically important differences in pain scores were identified, the clinical benefit of routine use of TXA in patients undergoing HTO is uncertain. Our study was too small to make safety-related claims on rare endpoints such as wound complications or thromboembolic events. Larger, and preferably randomized, trials are needed to help define whether it is important to use TXA in this setting. Our data can help inform sample size calculations for such studies., Level of Evidence: Level III, therapeutic study.

Use of biotrickling filter (BTF) for gas phase treatment of volatile trihalomethanes (THMs) stripped from water treatment plants could be an attractive treatment option. The aim of this study is to use laboratory-scale anaerobic BTF to treat gaseous chloroform (recalcitrant to biological transformation) as a model THM and compare results with aerobic BTF. Additional investigations were conducted to determine the microbial diversity present within the BTFs. Chloroform is a hydrophobic volatile THM known to be difficult to biodegrade. To improve the degradation process, ethanol was used as a cometabolite at a different ratio to chloroform. The experimental plan was designed to operate one BTF under anaerobic condition and the other one under aerobic acidic condition. Higher elimination capacity (EC) of 0.23 ± 0.01 g/[m 3 ·h] was observed with a removal efficiency of 80.9% ± 4% for the aerobic BTF operating at pH 4 for the concentration ratio of 1:40 chloroform to ethanol. For similar ratio, the anaerobic BTF supported lower removal efficiency of 59% ± 10% with corresponding lower EC of 0.16 ± 0.01 g/[m 3 ·h]. Carbon recovery acquired for anaerobic and aerobic BTFs was 59% and 63%, respectively. The loading rate for chloroform on both BTFs was 0.27 g/[m 3 ·h] (per m 3 of filter bed volume). Variations of the microbial community were attributed to degradation of chloroform in each BTF. Azospira oryzae and Azospira restrica were the dominant bacteria and potential candidates for chloroform degradation for the anaerobic BTF, whereas Fusarium sp. and Fusarium solani were the dominant fungi and potential candidates for chloroform degradation in the aerobic BTF.

Cardiopulmonary bypass (CPB) induces inflammatory responses, and effective endogenous homeostasis is important for preventing systemic inflammation. We assessed whether plasma exosomal microRNAs in patients undergoing cardiac surgery with CPB are involved in the regulation of inflammatory responses. Plasma samples were isolated from CPB patients (n = 21) at 5 specified time points: pre-surgery, pre-CPB and 2 hours (h), 4 h and 24 h after CPB began. Plasma TNF-α expression was increased after CPB began compared to that in the pre-surgery samples. Plasma IL-8 and IL-6 expression peaked at 4 h after CPB began but was downregulated at 24 h. The number of plasma exosomes collected at 2 h (55.1 ± 8.3%), 4 h (63.8 ± 10.1%) and 24 h (83.5 ± 3.72%) after CPB began was significantly increased compared to that in the pre-CPB samples (42.8 ± 0.11%). These exosomes had a predominantly parental cellular origin from RBCs and platelets. Additionally, the plasma exosomal miR-223 levels were significantly increased after CPB began compared to those in the pre-CPB samples. Further, exosomal miR-223 from plasma collected after CPB began downregulated IL-6 and NLRP3 expression in the monocytes. Here, we present the novel findings that increased plasma exosomal miR-223 expression during cardiac surgery with CPB might play homeostatic roles in downregulating inflammatory responses through intercellular communication.

Induction of fetal hemoglobin (HbF) is a promising strategy in the treatment of β-thalassemia major (β-TM). The present study shows that plasma exosomal miRNAs (exo-miRs) are involved in γ-globin regulation. Exosomes shuttle miRNAs and mediate cell-cell communication. MiRNAs are regulators of biological processes through post-transcriptional targeting. Compared to HD (Healthy Donor), β-TM patients showed increased levels of plasma exosomes and the majority of exosomes had cellular origin from CD34+ cells. Further, HD and β-TM exosomes showed differential miRNA expressions. Among them, deregulated miR-223-3p and miR-138-5p in β-TM exosomes and HD had specific targets for γ-globin regulator and repressor respectively. Functional studies in K562 cells showed that HD exosomes and miR-138-5p regulated γ-globin expression by targeting BCL11A. β-TM exosomes and miR-223-3p down regulated γ-globin expression through LMO2 targeting. Importantly, miR-223-3p targeting through sponge repression resulted in γ-globin activation. Further, hnRNPA1 bound to stem-loop structure of pre-miR-223 and we found that hnRNPA1 knockdown or mutagenesis at miR-223-3p stem-loop sequence resulted in less mature exo-miR-223-3p levels. Altogether, the study shows for the first time on the important clinical evidence that differentially expressed exo-miRNAs reciprocally control γ-globin expressions. Further, the hnRNPA1-exo-miR-223-LMO2 axis may be critical to γ-globin silencing in β-TM.

PIWI subfamily of proteins is shown to be primarily expressed in germline cells. They maintain the genomic integrity by silencing the transposable elements. Although the role of PIWI proteins in germ cells has been documented, their presence and function in somatic cells remains unclear. Intriguingly, we detected all four members of PIWI-like proteins in human ocular tissues and somatic cell lines. When HIWI2 was knocked down in retinal pigment epithelial cells, the typical honeycomb morphology was affected. Further analysis showed that the expression of tight junction (TJ) proteins, CLDN1, and TJP1 were altered in HIWI2 knockdown. Moreover, confocal imaging revealed disrupted TJP1 assembly at the TJ. Previous studies report the role of GSK3β in regulating TJ proteins. Accordingly, phospho-kinase proteome profiler array indicated increased phosphorylation of Akt and GSK3α/β in HIWI2 knockdown, suggesting that HIWI2 might affect TJ proteins through Akt-GSK3α/β signaling axis. Moreover, treating the HIWI2 knockdown cells with wortmannin increased the levels of TJP1 and CLDN1. Taken together, our study demonstrates the presence of PIWI-like proteins in somatic cells and the possible role of HIWI2 in preserving the functional integrity of epithelial cells probably by modulating the phosphorylation status of Akt.

Aims: Carvedilol phosphate (CDP) is a nonselective beta-blocker used for the treatment of heart failures and hypertension. In this work, moisture sorption-desorption characteristics and thermodynamic properties of CDP have been investigated., Materials and Methods: The isotherms were determined using dynamic vapor sorption analyzer at different humidity conditions (0%-90% relative humidity) and three pharmaceutically relevant temperatures (20°C, 30°C, and 40°C). The experimental sorption data determined were fitted to various models, namely, Brunauer-Emmett-Teller; Guggenheim-Anderson-De Boer (GAB); Peleg; and modified GAB. Isosteric heats of sorption were evaluated through the direct use of sorption isotherms by means of the Clausius-Clapeyron equation., Statistical Analysis Used: The sorption model parameters were determined from the experimental sorption data using nonlinear regression analysis, and mean relative percentage deviation (P), correlation (Correl), root mean square error, and model efficiency were considered as the criteria to select the best fit model., Results: The sorption-desorption isotherms have sigmoidal shape - confirming to Type II isotherms. Based on the statistical data analysis, modified GAB model was found to be more adequate to explain sorption characteristics of CDP. It is noted that the rate of adsorption and desorption is specific to the temperature at which it was being studied. It is observed that isosteric heat of sorption decreased with increasing equilibrium moisture content., Conclusions: The calculation of the thermodynamic properties was further used to draw an understanding of the properties of water and energy requirements associated with the sorption behavior. The sorption-desorption data and the set of equations are useful in the simulation of processing, handling, and storage of CDP and further behavior during manufacture and storage of CDP formulations., Competing Interests: There are no conflicts of interest.

In this paper, the application of biofiltration is investigated for controlled removal of gas phase chloroform through cometabolic degradation with ethanol. A trickle bed air biofilter (TBAB) operated under acidic pH 4 is subjected to aerobic biodegradation of chloroform and ethanol. The TBAB is composed of pelleted diatomaceous earth filter media inoculated with filamentous fungi species, which served as the principle biodegrading microorganism. The removal efficiencies of 5 ppm v of chloroform mixed with different ratios of ethanol as cometabolite (25, 50, 100, 150, and 200 ppm v ) ranged between 69.9 and 80.9%. The removal efficiency, reaction rate kinetics, and the elimination capacity increased proportionately with an increase in the cometabolite concentration. The carbon recovery from the TBAB amounted to 69.6% of the total carbon input. It is postulated that the remaining carbon contributed to excess biomass yield within the system. Biomass control strategies such as starvation and stagnation were employed at different phases of the experiment. The chloroform removal kinetics provided a maximum reaction rate constant of 0.0018 s -1 . The highest ratio of chemical oxygen demand (COD) removal /nitrogen utilization was observed at 14.5. This study provides significant evidence that the biodegradation of a highly chlorinated methane can be favored by cometabolism in a fungi-based TBAB.

The aim of the current exertion was to prepare Solid Dispersion of Etravirine by Spray drying technique to enhance aqueous solubility and dissolution rate. Solid dispersions (SD) of Etravirine were prepared using Copovidone and Povidone-Copovidone in dichloromethane and physical properties were characterized by Scanning electron microscopy (SEM), X-Ray diffractometry (PXRD), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC). SD's were evaluated for equilibrium solubility and in vitro drug release profile by dissolution testing. The diffraction and thermal patterns of solid dispersions indicated the conversion of crystalline Etravirine to amorphous form. The solubility of drug in SD's was appreciably more when evaluated against physical mixtures and intact Etravirine. Drug release characteristics were evaluated in three different media at different pH and found that drug release kinetic was best described by weibull mathematical model. Mean dissolution time (MDT) and Dissolution efficiency (DE %) in different media were evaluated for SDs. Statistical evaluation of dissolution data using Analysis Of Variance (ANOVA) single factor and t-Test: Paired Two Sample for Means was applied for better understanding and evaluation.

A three dimensional vanadium pentoxide/reduced graphene oxide/carbon nanotube (3D V2O5/RGO/CNT) composite is synthesized by microwave-assisted hydrothermal method. The combination of 2D RGO and 1D CNT establishes continuous 3D conductive network, and most notably, the 1D CNT is designed to form hierarchically porous structure by penetrating into V2O5 microsphere assembly constituted of numerous V2O5 nanoparticles. The highly porous V2O5 microsphere enhances electrolyte contact and shortens Li(+) diffusion path as a consequence of its developed surface area and mesoporosity. The successive phase transformations of 3D V2O5/RGO/CNT from α-phase to ε-, δ-, γ-, and ω-phase and its structural reversibility upon Li(+) intercalation/de-intercalation are investigated by in situ XRD analysis, and the electronic and local structure reversibility around vanadium atom in 3D V2O5/RGO/CNT is observed by in situ XANES analysis. The 3D V2O5/RGO/CNT achieves a high capacity of 220 mAh g(-1) at 1 C after 80 cycles and an excellent rate capability of 100 mAh g(-1) even at a considerably high rate of 20 C. The porous 3D V2O5/RGO/CNT structure not only provides facile Li(+) diffusion into bulk but contributes to surface Li(+) storage as well, which enables the design of 3D V2O5/RGO/CNT composite to become a promising cathode architecture for high performance LIBs.

Biocompatible nanoparticles are good candidates to label bacteria for imaging and diagnosis purposes. A high labeling efficiency reduces the concentration of nanoparticles required for labeling and allows the labeled bacteria to be tracked for longer periods. This report explores the optimal labeling strategy for Pseudomonas aeruginosa, a common gram-negative opportunistic pathogen, with quantum dots. Three strategies including direct incubation, calcium chloride treatment, and heat shock are compared and the labeling efficiency is assessed through fluorescence microscopy and flow cytometry analysis. Of the three, heat shock is finally selected due to its comparable labeling efficiency and simplicity. Through the assay of the respiration rate of bacteria together with morphology analysis, the heat shock process does not show any negative effect over the cells activity even at sub-toxic concentrations., (Copyright © 2016 Elsevier B.V. All rights reserved.)

RANTES (Regulated on activation, normal T-cell expressed and secreted), recruits circulating leukocytes and augments inflammatory responses in many clinical conditions. Inflammatory responses in ischemia-reperfusion injury (IRI) significantly affect the unfavorable outcomes of acute kidney injury (AKI), and that infiltrating immune cells are important mediators of AKI. However, the significance of RANTES in AKI and whether hypoxia-induced LncRNAs are involved in the regulatory process of AKI are not known. Here we show that, in the kidney IRI mice model, significant RANTES expression was observed in renal tubular cells of wild type mice. RANTES deficient (RANTES(-/-)) mice showed better renal function by reducing the acute tubular necrosis, serum creatinine levels, infiltration of inflammatory cells and cytokine expressions compared to wild type. In vitro, we found that RANTES expression was regulated by NF-κB. Further, renal tubular cells showed deregulated LncRNA expression under hypoxia. Among HIF-1α dependent LncRNAs, PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress) was significantly up regulated in hypoxic conditions and had specific interaction with RANTES as confirmed through reporter assay. These observations show first evidence for RANTES produced by renal tubular cells act as a key chemokine in AKI and HIF-1α regulated LncRNA-PRINS might be involved in RANTES production.

Efavirenz is a non-nucleoside reverse transcriptase inhibitor used in the treatment of human immunodeficiency virus type-1 (HIV). (2S)-(2-Amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol (AMCOL), used as an intermediate in the synthesis of efavirenz and a degradation impurity, has an aminoaryl derivative which is a well-known alerting function for genotoxic activity. Upon request from a regulatory agency, a selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for trace level quantitative determination of AMCOL related compound of efavirenz, for a risk assessment and comparison of impurity levels with the commercially available innovator product (brand name: Sustiva). The method provided excellent sensitivity at a typical target analyte level of <2.5 ppm, an established threshold of toxicological concern (TTC), when the drug substance and drug product samples were prepared at 15.0 mg/mL. The AMCOL sample was analyzed on a Luna C18 (2) (100 mm × 4.6 mm, 3 µm) column interfaced with a triple quadrupole tandem mass spectrometer operated in a multiple reaction monitoring (MRM) mode. Positive electrospray ionization (ESI) was employed as the ionization source and the mobile phase used was 5.0 mM ammonium acetate-methanol (35:65, v/v). The calibration curve showed good linearity over the concentration range of 0.2-5.0 ppm with a correlation coefficient of >0.999. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.07 and 0.2 ppm, respectively. The developed method was validated as per international council on harmonization (ICH) guidelines in terms of LOD, LOQ, linearity, precision, accuracy, specificity, and robustness., Competing Interests: The authors declare no conflict of interest.

Background and Purpose: Oxidative stress and subsequent activation of inflammatory responses is a widely accepted consequence of exposure to environmental toxins. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a well-known environmental toxin, exerts its toxicity through many signalling mechanisms, with liver being the principal organ affected. However, an effective antidote to TCDD-induced toxicity is unknown. The present study evaluated the effect of eicosapentaenoic acid (EPA), an n3 fatty acid, on TCDD-induced toxicity., Experimental Approach: In cultures of HepG2 cells, the EPA/AA ratio was determined using gas chromatography, oxidative stress and inflammatory responses through reactive oxygen species (ROS) levels, antioxidant status, [Ca(2+) ]i , nuclear migration of two redox-sensitive transcription factors, NF-κB p65 and Nrf-2, expression of MAP kinase (p-Erk, p-p38), NF-κB p65, COX-2 and Nrf-2. Cellular changes in ΔΨm, acidic vesicular organelle formation, cell cycle analysis and scanning electron microscopy analysis were performed., Key Results: EPA offered significant cytoprotection by increasing EPA/AA ratios in cell membranes, inhibiting ROS generation, enhancing antioxidant status and modulating nuclear translocation of redox-sensitive transcription factors (NF-κB p65 and Nrf-2) and expression of NF-κB p65, COX-2 and Nrf-2. Furthermore, TCDD-induced upstream events of MAPK phosphorylation, the increase in [Ca(2+) ]i levels and cell surface changes in microvilli were significantly inhibited by EPA. EPA treatment maintained ΔΨm and prevented formation of acidic vesicular organelles., Conclusion and Implications: The present study demonstrates for the first time some underlying molecular mechanisms of cytoprotection exerted by EPA against TCDD-induced oxidative stress and inflammatory responses., (© 2015 The British Pharmacological Society.)

Background: Lipase is an enzyme with immense application potential. Ester synthesis by lipase catalysis in organic media is an area of key industrial relevance. Enzymatic preparations with traits that cater to the needs of this function are hence being intensely researched., Objective: The objectives of the study were to immobilize the lipase from Bacillus sp. PS35 by cross-linking and adsorption onto styrene-divinyl benzene (Sty-Dvb) hydrophobic resin and to comparatively characterize the free and immobilized lipase preparations. The work also aimed to apply the immobilized lipase for catalysing the fatty acid methyl ester (FAME) synthesis from palm oil and optimize the process parameters for maximizing the yield., Materials and Methods: In this study, the purified lipase from Bacillus sp. PS35 was immobilized by adsorption onto styrene-divinyl benzene hydrophobic resin with gluteraldehyde cross-linking., Results: The immobilized enzyme showed better pH and temperature stabilities than the free lipase. Organic solvent stability was also enhanced, with the relative activity in the presence of methanol being shifted from 53% to 81%, thereby facilitating the enzyme's application in fatty acid methyl ester synthesis. It exhibited remarkable storage stability over a 30-day period and after 20 repetitive uses. Cross-linking also reduced enzyme leakage by 49%. The immobilized lipase was then applied for biodiesel production from palm oil. Methanol and oil molar ratio of 5:1, three step methanol additions, and an incubation temperature of 50°C were established to be the ideal conditions favoring the transesterification reaction, resulting in 97% methyl ester yield., Conclusions: These promising results offer scope for further investigation and process scale up, permitting the enzyme's commercial application in a practically feasible and economically agreeable manner., Competing Interests: The authors have no substantial financial or commercial conflicts of interest with the current work or its publication.

Objective: In the present study, simultaneous determination of degree of crystallinity content in abacavir (ABC), lamivudine (3TC) and neverapine (NVP) from there combination drug product using X-ray powder diffraction (XRPD) technique is developed and validated., Methods: The X-ray procedure for the identification and determination of the degree of crystallinity in ABC, 3TC and NVP drug product is developed and validated. It is based on the X-ray diffraction from crystalline region of the drug product. The characteristic peaks of the three drugs were characterized using XRPD., Results: ABC, 3TC and NVP concentrations ranging from 70% to 130% in drug product were prepared and linearity in this concentration range is described. The % coefficient of variation (%CV) was found to be 0.9982 for ABC, 0.9978 for 3TC and 0.9984 for NVP. The mean recoveries were found to be 100.3% for ABC, 99.0% for 3TC and 100.8% for NVP. Regressions statistics and Analysis of variance (ANOVA) table results were evaluated and found to be satisfactory., Conclusions: The method has been applied to unknown mixtures of drug formulations and stability samples. The proposed method can be useful in the quality control of combination drug products.

Herein, we report a versatile solid phase synthesis approach for partial functionalization of gold nanoparticles (AuNPs) via the assistance of surfactant. Hexadecyl trimethyl ammonium bromide (CTAB) is used as the bifunctional ligand to link the solid substrate and the AuNPs. This brings at least two advantages comparing to other bifunctional ligands: first, the thickness of the CTAB bilayer is flexible. During the "catch" process, the bilayer bound on different sites of the AuNPs could shrink or extend to a total thickness difference of ~2.5 nm, which protects a spherical cap of the AuNPs with the height of ~2.5 nm from chemical modification; second, after chemical modification, the "release" of the AuNPs from the substrate is quite simple. Not any second ligand, but only sonication is enough to release the AuNPs. As a result, the proposed approach produces partially functionalized AuNPs with a large surface area (80-95%) covered with unreactive ligands, while keeps the other small spatially limited region of the surface unmodified. This small unmodified surface can be directly used for further chemistry. Finally, the partially modified AuNPs is demonstrated for a one-step synthesis of AuNP dimers., (Copyright © 2013 Elsevier Inc. All rights reserved.)