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Pseudomonas aeruginosa is an opportunistic human pathogen responsible for acute and chronic, hard to treat infections. Persistence of P. aeruginosa is due to its ability to develop into biofilms, which are sessile bacterial communities adhered to substratum and encapsulated in layers of self-produced exopolysaccharides. These biofilms provide enhanced protection from the host immune system and resilience towards antibiotics, which poses a challenge for treatment. Various strategies have been expended for combating biofilms, which involve inhibiting biofilm formation or promoting their dispersal. The current remediation approaches offer some hope for clinical usage, however, treatment and eradication of preformed biofilms is still a challenge. Thus, identifying novel targets and understanding the detailed mechanism of biofilm regulation becomes imperative. Structure-based drug discovery (SBDD) provides a powerful tool that exploits the knowledge of atomic resolution details of the targets to search for high affinity ligands. This review describes the available structural information on the putative target protein structures that can be utilized for high throughput in silico drug discovery against P. aeruginosa biofilms. Integrating available structural information on the target proteins in readily accessible format will accelerate the process of drug discovery. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare conventional and tissue Doppler echocardiography parameters between transient tachypnea of the newborn (TTN) and healthy control infants. This cross sectional pilot observational study was conducted in a level 3 neonatal care unit of India. Consecutively born late preterm and term infants (LPTI) with TTN were eligible for enrollment. Control group was selected from healthy LPTI. Conventional and tissue Doppler (myocardial velocities, myocardial performance index (MPI)) echocardiography was done within first 12 h (D1) and 48–72 h (D3) of life. Conventional echocardiography parameters were fractional shortening (FS), ejection fraction (EF), ventricular output, E/A ratio, fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), pulmonary artery systolic pressure (PASP), and pulmonary artery acceleration to ejection time ratio (PATET). Baseline characteristics and echocardiography images were compared between TTN and control groups. Out of 60 infants enrolled, 34 from TTN and 20 from control group were finally analyzed. Mean (SD) gestational age and birth weight of the study population was 366/7(1.8) weeks and 2398(376) g respectively. Left ventricular (LV) parameters were similar between both groups. On D1, right ventricular (RV)e' was smaller (6.42(1) cm/s vs. 7.68(1.68) cm/s, p 0.022), and E/e' (7.79(1.51) vs. 6.08(2.59), p 0.037) was larger in TTN group, indicating RV diastolic dysfunction. RV MPI (0.61(0.11) vs. 0.44(0.12), p < 0.001) was also larger, signifying RV global myocardial dysfunction. Similar findings were observed on D3. PATET was lower in TTN group on both D1 (0.34 (0.05) vs. 0.42 (0.05), p < 0.001) and D3 (0.38 (0.05) vs. 0.43 (0.02), p 0.004) suggesting persistently raised pulmonary arterial pressure, although only 2 infants developed pulmonary hypertension identified by standard echocardiography. Conclusion: Myocardial tissue Doppler imaging of TTN infants revealed occult right ventricular diastolic dysfunction secondary to persistently raised pulmonary arterial pressure. What is Known: •Transient tachypnea of the newborn may be associated with pulmonary arterial hypertension. What is New: •Tissue Doppler imaging in infants with transient tachypnea of the newborn revealed occult right ventricular diastolic dysfunction secondary to raised pulmonary arterial pressure, not detected by standard echocardiography. [ABSTRACT FROM AUTHOR]

The elevation of carbon dioxide (CO2) levels in the atmosphere is responsible for global warming which in turn causes abrupt climate change and consequently poses a threat to living organisms in the coming years. To reduce CO2 content in the atmosphere CO2 capture and separation is highly necessary. Among various methods of CO2 capture post-combustion capture is very much useful because of its operational simplicity and applicability in many industries and power sectors, such as coal-fired power plants. Polymers with high surface area, high volume and narrow pores are ideal solid sorbents for adsorption-driven post-combustion CO2 capture. Natural polymers, such as polysaccharides are cheap, abundant, and can be modified by various methods to produce porous materials and thus can be effectively utilized for CO2 capture while the surface area and the pore size of synthetic porous organic polymers can be tuned precisely for high CO2 capturing capacity. A significant amount of research activities has already been established in this field, especially in the last ten years and are still in progress. In this review, we have introduced the latest developments to the readers about synthetic techniques, post-synthetic modifications and CO2 capture capacities of various biopolymer-based materials and synthetic porous organic polymers (POPs) published in the last five years (2018–2022). This review will be beneficial to the researchers to design smart polymer-based materials to overcome the existing challenges in carbon capture and storage/sequestration. [ABSTRACT FROM AUTHOR]

The cobalt pyridinophane complex [Co(HN4)Cl2]+ (HN4 = 3,7-diaza-1,5(2,6)-dipyridinacyclooctaphane) is converted under catalytic conditions to an electrode-adsorbed species. Aqueous Co2+ solutions similarly deposit a species under these conditions. Surface characterization reveals the formation of Co nanoparticles. These nanoparticles are active in the electrocatalytic redution of aqueous nitrate. [ABSTRACT FROM AUTHOR]

This article describes the synthesis of optically pure four N -Boc and N -Cbz-protected (R) - and (S) - isomers of Garner's aldehyde. The key step involves TiCl 4 -catalyzed Evans' aldol reaction of the uncommon chiral synthon "glycine enolate equivalent" of N-(N -Boc/Cbz-glycinyl) oxazolidinone with gaseous formaldehyde. The chromatographically separable Evans and non-Evans adduct formation takes place through the installation of hydroxymethyl functionality on chiral glycine enolate in good yields. The orthogonality of the reaction was maintained via the "reverse addition" in the aldol reaction on Evans chiral auxiliary. This method provides a promising opportunity for the synthesis of expensive (R)-Garner's aldehyde evading the use of unnatural d -serine. Moreover, asymmetric alkylation of Li-enolate of N-(N- Boc-glycinyl) oxazolidinone is a promising opportunity for the formation of an exclusive single isomer of (R)-Garner's aldehyde. [Display omitted] [ABSTRACT FROM AUTHOR]

The present study investigates the impact of monsoon on meiofaunal and free-living nematode communities of the Sundarban estuarine system (SES) both from taxonomic and functional point of view. In 2013, SES experienced an unusual rainfall event followed by cloud burst event at upper Himalayan regime. Average meiobenthic abundance declined considerably in the study area from early phase of monsoon (EM) (699 ± 1569.4 ind. 10 cm −2 ) to later one (LM) (437 ± 949.9 ind. 10 cm −2 ) probably due to high annual rainfall which completely flushed the estuary. Free-living marine nematodes were the dominant group among all other meiobenthic taxa in both phases of monsoon. Nematode community was made up of 49 genera in 22 families. Comesomatidae, Chromadoridae, Linhomoeidae and Xylidae were the richest and most abundant families. During both phases of monsoon, stations, which were represented by fine sediments and high amount of organic carbon, harbored higher meiofaunal densities and nematode diversity with a strong dominance of 1B and 2B trophic guilds of nematodes. Different feeding guilds of nematode would be able to reveal anthropogenic-induced stress, which could be useful in assessing ecological quality of estuarine ecosystems. The present study indicates that climate change mediated unusual monsoonal precipitation may notoriously affect the meiobenthic assemblages in tropical estuaries like SES. Thus, this study could be an important first stepping stone for monitoring the future environmental impact on meiobenthic community in the largest mangrove region of the world. [ABSTRACT FROM AUTHOR]

Hydrogels are promising candidates for biomimetic scaffolds of the extracellular matrix in tissue engineering applications. However, their use in bone tissue engineering is limited due to their low mechanical properties. In this study, we designed and synthesized multicomponent peptide-based hydrogels composed of fluorenyl-9-methoxycarbonyl diphenylalanine (FmocFF), which contributed to the rigidity and stability of the hydrogel, and Fmoc-arginine (FmocR), which mediated high affinity to hydroxyapatite (HAP) due to the arginine moiety. The new hydrogels composed of nanometric fibril networks were decorated with HAP and demonstrated high mechanical strength with a storage modulus of up to 29 kPa. In addition, the hydrogels supported cell adhesion and in vitro cell viability. These properties suggest using these multicomponent organic-inorganic hydrogels as functional biomaterials for improved bone regeneration. [ABSTRACT FROM AUTHOR]

Molecular self-assembly is a key direction for the fabrication of advanced materials. Yet, the physical properties of the formed assemblies are limited by the inherent characteristics of the specific building blocks. Here, we have applied a co-assembly approach to synergistically modulate the mechanical properties of peptide hydrogels, thereby forming extremely stable and rigid hydrogels. [ABSTRACT FROM AUTHOR]

Due to their photoluminescence, metal oxide nanostructures such as ZnO nanostructures are promising candidates in biomedical imaging, drug delivery and bio-sensing. To apply them as label for bio-imaging, it is important to study their structural stability in a bio-fluidic environment. We have explored the effect of water, the main constituent of biological solutions, on ZnO nanostructures with scanning electron microscopy (SEM) and photoluminescence (PL) studies which show ZnO nanorod degeneration in water. In addition, we propose and investigate a robust and inexpensive method to encapsulate these nanostructures (without structural degradation) using bio-compatible non-ionic surfactant in non-aqueous medium, which was not reported earlier. This new finding is an immediate interest to the broad audience of researchers working in biophysics, sensing and actuation, drug delivery, food and cosmetics technology, etc. [ABSTRACT FROM AUTHOR]

Mechanical properties of nanocrystals are influenced by atomic defects. Here, we demonstrate the effect of planar defects on the mechanics of ZnO nanorods using atomic force microscopy, high-resolution transmission electron microscopy, and large-scale atomistic simulation. We study two different conditionally grown single nanorods. One contains extended I1-type stacking fault (SF) and another is defect free. The SF containing nanorods show buckling behaviors with reduced critical loading, whereas the other kinds show linear elastic behavior. We also studied the size dependence of elastic modulus and yield strength. The elastic modulus in both nanorods is inversely proportional to their size. Similar trend is observed for yield strength in the SF containing nanorods; however, the opposite is observed in the SF-free nanorods. This first experimental and theoretical study will guide toward the development of reliable electromechanical devices. [ABSTRACT FROM AUTHOR]

Trimesic acid based amino acid functionalized triple tailed amphiphiles (TMA-1 and TMA-2) were synthesized. The triskelion amphiphile TMA-1 with a neutral side chain self-assembled into a vesicle in 2:1 (v/v) DMSO-water, while the ammonium side chain decorated TMA-2 formed vesicles in pure water. Microscopic and spectroscopic characterizations were carried out to confirm the self-aggregated vesicular morphology and its size which is around 250-300 nm in the case of TMA-1 and around 100-150 nm for TMA-2 vesicles. The unique structure of these amphiphiles with an aromatic core and three hydrophilic side chains led to an interlamellar orientation of their hydrophobic (aromatic) domain, while hydrophilic terminals were directed toward the aqueous domain. These amphiphiles formed monolayered vesicles possibly through H-aggregation during the process of self-assembly, which is different from conventional bilayered vesicles formed by twin-chain lipid molecules. The time resolved decay curve of hydrophobic dye entrapped within these vesicles indicated that the hydrophobicity within the microenvironment of TMA-1 and TMA-2 vesicles is higher than that in pure water; however, at the same time, it is comparatively lower than that observed in bilayered phosphocholine vesicles. Furthermore, calcein dye was entrapped within these vesicles to ensure their encapsulation efficiency (65-85%). The ability to entrap dye molecules by these synthesized vesicles was utilized to encapsulate and deliver anticancer drug doxorubicin inside the mammalian cells. A simple synthetic procedure and facile aggregation to vesicular self-assembly with superior dye/drug encapsulation proficiency made these vesicles a potential cellular transporter. [ABSTRACT FROM AUTHOR]

The present work reports the synthesis of a 17β-estradiol based amphiphiles comprising of polyethylene glycol (PEG) moiety linked through succinic acid that non-covalently dispersed (76%) the single walled carbon nanotubes (SWNTs) in water. The superior exfoliation of carbon nanotubes was characterized by microscopic and spectroscopic studies. Significant stability of these SWNT dispersions was observed in the presence of protein in cell culture media and the nanohybrids were highly biocompatible toward mammalian cells. Anticancer drug doxorubicin loaded on these nanohybrids was selectively delivered within estrogen receptor rich cancer cells, MCF7 (breast cancer cell) and A549 (lung cancer cell). Microscopic studies showed the localization of doxorubicin within the cancer cell nucleus whereas no such localization was observed in ER negative cells. Both these ER positive cancer cells were killed by ∼3 fold higher efficiency than that of ER negative MDA-MB-231 (advanced breast cancer cell) and HeLa cells that are deprived of estrogen receptors. Thus, judiciously designed estradiol based nanohybrids proved to be excellent tool for SWNT dispersion and also for selectively killing of ER positive cancer cells. To the best of our knowledge, for the first time non-covalently modified SWNTs by estradiol based amphiphilic dispersing agent have been used for selective killing of ER positive cancer cells by doxorubicin loaded on dispersed SWNTs. It holds immense promise to be exploited as a cancer therapeutic agent. [ABSTRACT FROM AUTHOR]

Ferroelectricity in ZnO is an unlikely physical phenomenon. Here, we show ferroelectricity in undoped [001] ZnO nanorods due to zinc vacancies. Generation of ferroelectricity in a ZnO nanorod effectively increases its piezoelectricity and turns the ZnO nanorod into an ultrahigh-piezoelectric material. Here using piezoelectric force microscopy (PFM), it is observed that increasing the frequency of the AC excitation electric field decreases the effective d33. Subsequently, the existence of a reversible permanent electric dipole is also found from the P–E hysteresis loop of the ZnO nanorods. Under a high resolution transmission electron microscope (HRTEM), we observe a zinc blende stacking in the wurtzite stacking of a single nanorod along the growth axis. The zinc blende nature of this defect is also supported by the X-ray diffraction (XRD) and Raman spectra. The presence of zinc vacancies in this basal stacking fault modulates p–d hybridization of the ZnO nanorod and produces a magnetic moment through the adjacent oxygen ions. This in turn induces a reversible electric dipole in the non-centrosymmetric nanostructure and is responsible for the ultrahigh-piezoelectric response in these undoped ZnO nanorods. We reveal that this defect engineered ZnO can be considered to be in the competitive class of ultrahigh-piezoelectric nanomaterials for energy harvesting and electromechanical device fabrication. [ABSTRACT FROM AUTHOR]

Squamous cell lung cancer (SCC) is the second leading cause of lung cancer death in the US and has a 5-year survival rate of only 16%. Histological changes in the bronchial epithelium termed dysplasia are precursors to invasive SCC. However, the cellular mechanisms that cause dysplasia are unknown. To fill this knowledge gap, we used topical application of N-nitroso-tris chloroethylurea (NTCU) for 32 weeks to induce squamous dysplasia and SCC in mice. At 32 weeks the predominant cell type in the dysplastic airways was Keratin (K) 5 and K14 expressing basal cells. Notably, basal cells are extremely rare in the normal mouse bronchial epithelium but are abundant in the trachea. We therefore evaluated time-dependent changes in tracheal and bronchial histopathology after NTCU exposure (4, 8, 12, 16, 25 and 32 weeks). We show that tracheal dysplasia occurs significantly earlier than that of the bronchial epithelium (12 weeks vs. 25 weeks). This was associated with increased numbers of K5+/K14+ tracheal basal cells and a complete loss of secretory (Club cell secretory protein expressing CCSP+) and ciliated cells. TUNEL staining of NTCU treated tissues confirmed that the loss of CCSP+ and ciliated cells was not due to apoptosis. However, mitotic index (measured by bromodeoxyuridine incorporation) showed that NTCU treatment increased proliferation of K5+ basal cells in the trachea, and altered bronchial mitotic population from CCSP+ to K5+ basal cells. Thus, we demonstrate that NTCU-induced lung epithelial dysplasia starts in the tracheal epithelium, and is followed by basal cell metaplasia of the bronchial epithelium. This analysis extends our knowledge of the NTCU-SCC model by defining the early changes in epithelial cell phenotypes in distinct airway locations, and this may assist in identifying new targets for future chemoprevention studies. [ABSTRACT FROM AUTHOR]

Background: The protozoan parasite Leishmania donovani (LD) reduces cellular cholesterol of the host possibly for its own benefit. Cholesterol is mostly present in the specialized compartment of the plasma membrane. The relation between mobility of membrane proteins and cholesterol depletion from membrane continues to be an important issue. The notion that leishmania infection alters the mobility of membrane proteins stems from our previous study where we showed that the distance between subunits of IFNγ receptor (R1 and R2) on the cell surface of LD infected cell is increased, but is restored to normal by liposomal cholesterol treatment. Methodology/Principal Findings: We determined the lateral mobility of a membrane protein in normal, LD infected and liposome treated LD infected cells using GFP-tagged PLCδ1 as a probe. The mobility of PLCδ1 was computationally analyzed from the time lapse experiment using boundary distance plot and radial profile movement. Our results showed that the lateral mobility of the membrane protein, which is increased in infection, is restored to normal upon liposomal cholesterol treatment. The results of FRAP experiment lent further credence to the above notion. The membrane proteins are intimately linked with cellular actin and alteration of cellular actin may influence lateral mobility. We found that F-actin is decreased in infection but is restored to normal upon liposomal cholesterol treatment as evident from phalloidin staining and also from biochemical analysis by immunoblotting. Conclusions/Significances: To our knowledge this is the first direct demonstration that LD parasites during their intracellular life cycle increases lateral mobility of membrane proteins and decreases F-actin level in infected macrophages. Such defects may contribute to ineffective intracellular signaling and other cellular functions. Author Summary: The protozoan parasites, Leishmania donovani, replicate within the macrophages of the mammalian hosts. During its intracellular lifecycle, the parasite induces a wide variety of defects in the membrane homeostasis. Membrane bound receptor molecules are important for interacting with external stimuli. Our study very clearly showed that there is an increase in the mobility of membrane protein coupled with decrease in F-actin in infected cells, which may be corrected by liposomal cholesterol treatment. This observation indicates that intracellular parasite may alter the membrane biology of infected cells which may dampen overall cellular function. [ABSTRACT FROM AUTHOR]

Background: The protozoan parasite Leishmania donovani (LD) reduces cellular cholesterol of the host possibly for its own benefit. Cholesterol is mostly present in the specialized compartment of the plasma membrane. The relation between mobility of membrane proteins and cholesterol depletion from membrane continues to be an important issue. The notion that leishmania infection alters the mobility of membrane proteins stems from our previous study where we showed that the distance between subunits of IFNγ receptor (R1 and R2) on the cell surface of LD infected cell is increased, but is restored to normal by liposomal cholesterol treatment. Methodology/Principal Findings: We determined the lateral mobility of a membrane protein in normal, LD infected and liposome treated LD infected cells using GFP-tagged PLCδ1 as a probe. The mobility of PLCδ1 was computationally analyzed from the time lapse experiment using boundary distance plot and radial profile movement. Our results showed that the lateral mobility of the membrane protein, which is increased in infection, is restored to normal upon liposomal cholesterol treatment. The results of FRAP experiment lent further credence to the above notion. The membrane proteins are intimately linked with cellular actin and alteration of cellular actin may influence lateral mobility. We found that F-actin is decreased in infection but is restored to normal upon liposomal cholesterol treatment as evident from phalloidin staining and also from biochemical analysis by immunoblotting. Conclusions/Significances: To our knowledge this is the first direct demonstration that LD parasites during their intracellular life cycle increases lateral mobility of membrane proteins and decreases F-actin level in infected macrophages. Such defects may contribute to ineffective intracellular signaling and other cellular functions. [ABSTRACT FROM AUTHOR]

Highlights: [•] Citrate capped GNPs were mixed with SWNT, dispersed with cationic amphiphile. [•] SWNT–GNP nanocomposite formation took place due to ion exchange. [•] SWNT–GNP nanocomposite doped CTAB water-in-oil (w/o)-microemulsion was developed. [•] The interfacial area of w/o-microemulsion got increased due to inclusion of SWNT–GNP. [•] Surface active lipase showed improved activity in SWNT–GNP doped w/o microemulsion. [Copyright &y& Elsevier]

Objectives The commonly used antileishmanial drugs are sodium antimony gluconate (SAG), amphotericin B, miltefosine and paromomycin. There are a number of reports that antileishmanial drugs show immunomodulatory properties. Here, we attempt to understand how the innate arm of the immune system is modulated in response to these antileishmanial drugs. Methods BALB/c peritoneal macrophages were treated with miltefosine, SAG, amphotericin B or paromomycin. The membrane fluidity of macrophages following drug treatment was studied in terms of fluorescence anisotropy. The T cell-stimulating ability, production of cytokines and nitrogen and oxygen metabolite production in drug-treated macrophages were also studied. The study was also carried out using peritoneal macrophages from drug-treated BALB/c mice. Results The antileishmanial drugs altered macrophage membrane fluidity, except amphotericin B. The drug-treated macrophages showed enhanced T cell-stimulating ability and generation of reactive oxygen species, nitrite, interleukin-12 and tumour necrosis factor-α. Conclusions Antileishmanial drugs can stimulate the innate arm of the immune system, which may have a significant bearing on the cellular arm of the immune system. [ABSTRACT FROM PUBLISHER]

Highlights: [•] Context of the carrier protein influences epitope immunodominance. [•] Endoproteolysis dictates epitope immunodominance. [•] Unfolding, a key determinant of endoproteolysis of an antigen. [•] This study lends credence to the notion that for rational design of peptide vaccine. [Copyright &y& Elsevier]

Background: Despite the huge proportion of the babies in the developing world being born low birthweight, only about half of the newborns are weighed at birth as weighing scales often tend to be either non-available or defective.Objective: Designing a nomogram for estimation of birthweight from head circumference (HC) and mid-upper arm circumference (MUAC).Method: Birthweight, HC and MUAC of 500 newborns who were admitted in the baby nursery of Medical College and Hospital, Kolkata between July 2010 to December 2010 were measured.Results: Multiple linear regression equation for prediction of birth weight from MUAC and HC was derived and a nomogram was constructed from the same.Conclusion: The birthweight estimation nomogram is an inexpensive and convenient tool for use in the community setting where weighing machines may not be always available and may thus allow prompt and early referral. [ABSTRACT FROM PUBLISHER]

Background: In developing countries, 80% of the births take place in the community. Methods: Birthweight, mid-arm and chest circumferences were measured in 294 newborns admitted in a tertiary-level hospital in Kolkata between April and August 2010. Colour-coded measuring tapes were devised using receiver operating characteristic curves to calculate the most sensitive and specific cut-off values to identify birthweight <2.5 and 1.8 kg. Result: There is no significant difference in accuracy of Mid-arm circumference (MAC) and Chest circumference (CC) for prediction of low birth weight and birthweight <1.8 kg. The tape has three zones, green [weight (wt) > 2.5 kg, MAC > 8.4 cm, CC > 30 cm], yellow (wt 2.5–1.8 kg, MAC 8.4–6.7 cm, CC 30–25.5 cm) indicating some risk, and red (wt < 1.8 kg, MAC < 6.7 cm, CC < 25.5 cm) indicating babies needing referral and admission in Level II neonatal care unit. [ABSTRACT FROM PUBLISHER]

Objectives: To assess the role of different factors that are associated with initiation and continuation of adolescent smoking. Materials and methods: A total of 2535 students (1465 males and 1070 females) between the age groups of 14 and 19 years were selected from four schools and two colleges of the city by two-stage cluster sampling design for this cross-sectional study. Results: The prevalence of cigarette smoking was 21.58%. Smoking was found to be considerably influenced with having seen best friend, father, sibling and favorite movie star smoke and also with receiving pocket money. Conclusion: Experimentation of substance use, motivated by family members, peer groups and the surrounding environment is common among adolescents and starts early in life. Therefore, it is necessary to come up with health promotion programs directed toward students which encourage attitude shaping among them toward self-confidence and healthy life style. [ABSTRACT FROM PUBLISHER]

Abstract: Endothelial dysfunction and cell death play an important role in pathogenesis of atherosclerosis. 7-Oxysterols, the major cytotoxic component found in oxidized low-density lipoprotein, are toxic to endothelial cells. However, the pathways and molecular mechanism involved in the process remain incompletely understood. In this study, we first investigate whether 7β-hydroxycholesterol (7βOH) or 7-ketocholesterol (7keto) induces apoptosis of human endothelial cell line (HUVEC-CS). We then examine possible involved pathways by focusing on cellular lipid, lysosomal pathways, cellular oxidative stress and mitochondrial pathways. Our results for the first time showed that 7-oxysterols induced apoptotic cell death of HUVEC-CS after 24h, which was preceded by early lipid accumulation (6h) and lysosomal membrane permeabilization (6−12h). Afterward, levels of reactive oxygen species, mitochondrial membrane permeabilization, and lysosomal cathepsin were increased assayed by immuno-cytochemistry and blotting. Notably, the exposure to 7βOH or 7keto induced expressions and secretion of isoforms of von Willebrand factor (VWF). We conclude that apoptosis of HUVEC-CS induced by 7βOH or 7keto mediates by early lysosomal lipid accumulation and oxidative lysosomal pathways, which results in induction and release of VWF. The results suggest the cell death induced by 7-oxysterols may contribute to endothelial dysfunction and atherothrombosis. [Copyright &y& Elsevier]

Abstract: Moderate lysosomal membrane permeabilization (LMP) is an important inducer of apoptosis. Macrophages are professional scavengers and are rich in hydrolytic enzymes and iron. In the present study, we found that LMP by lysosomotropic detergent MSDH resulted in early up-regulation of lysosomal cathepsins, oxidative stress and ferritin up-regulation, and cell death. Lysosomotropic base NH4Cl reduced the ferritin induction and oxidative stress in apoptotic cells induced by MSDH. Cysteine cathepsin inhibitors significantly protected cell death and oxidative stress, but had less effect on ferritin induction. We conclude that oxidative stress induced by lysosomal rupture causes ferritin induction with concomitant mitochondrial damage, which are the potential target for prevention of cellular oxidative stress and cell death induced by typical lysosomotropic substances in different disorders. [Copyright &y& Elsevier]

Abstract: This work reports the performance of high speed steel drill bits coated with TiAlSiN nanocomposite coating at different Si contents (5.5–8.1at.%) prepared using a four-cathode reactive pulsed direct current unbalanced magnetron sputtering system. The surface morphology of the as-deposited coatings was characterized using field emission scanning electron microscopy. The crystallographic structure, chemical composition and bonding structure were evaluated using X-ray diffraction, energy-dispersive X-ray analysis, X-ray photoelectron spectroscopy, respectively. The corrosion behavior, mechanical properties and thermal stability of TiAlSiN nanocomposite coatings were also studied using potentiodynamic polarization, nanoindentation and Raman spectroscopy, respectively. The TiAlSiN coating thickness was approximately 2.5–2.9μm. These coatings exhibited a maximum hardness of 38GPa at a silicon content of approximately 6.9at.% and were stable in air up to 850°C. For the performance evaluation, the TiAlSiN coated drills were tested under accelerated machining conditions by drilling a 12mm thick 304 stainless steel plate. Under dry conditions the uncoated drill bits failed after drilling 50 holes, whereas, TiAlSiN coated drill bits (Si=5.5at.%) drilled 714 holes before failure. Results indicated that for TiAlSiN coated drill bits the tool life increased by a factor of more than 14. [Copyright &y& Elsevier]

Group IVA cytosolic phospholipase A2 (cPLA[sub2]α) is regulated by phosphorylation and calcium-induced translocation to membranes. Immortalized mouse lung fibroblasts lacking endogenous cPLA[sub2]α (IMLF) were reconstituted with wild type and cPLA[sub2]α mutants to investigate how calcium, phosphorylation, and the putative phosphatidylinositol 4,5bisphosphate (PIP[sub2]) binding site regulate translocation and arachidonic acid (AA) release. Agonists that elicit distinct modes of calcium mobilization were used. Serum induced cPLA[sub2]α translocation to Golgi within seconds that temporally paralleled the initial calcium transient. However, the subsequent influx of extracellular calcium was essential for stable binding of cPLA[sub2]α to Golgi and AA release. In contrast, phorbol 12-myristate 13-acetate induced low amplitude calcium oscillations, slower translocation of cPLA[sub2]α to Golgi, and much less AA release, which were blocked by chelating extracellular calcium. AA release from IMLF[sup-/-] expressing phosphorylation site (S505A) and PIP[sub2] binding site (K488N/K543N/K544N) mutants was partially reduced compared with cells expressing wild type cPLA[sub2]α, but calcium-induced translocation was not impaired. Consistent with these results, Ser-505 phosphorylation did not change the calcium requirement for interfacial binding and catalysis in vitro but increased activity by 2-fold. Mutations in basic residues in the catalytic domain of cPLA[sub2]α reduced activation by PIP[sub2] but did not affect the concentration of calcium required for interfacial binding or phospholipid hydrolysis. The results demonstrate that Ser-505 phosphorylation and basic residues in the catalytic domain principally act to regulate cPLA[sub2]α hydrolytic activity. [ABSTRACT FROM AUTHOR]

Group IVA cytosolic phospholipase A2 (cPLA2α) initiates eicosanoid production; however, this pathway is not completely ablated in cPLA2α-/- lung fibroblasts stimulated with A23187 or serum. cPLA2α+/+ fibroblasts preferentially released arachidonic acid, but A23187-stimulated cPLA2α-/- fibroblasts non-specifically released multiple fatty acids. Arachidonic acid release from cPLA2-/- fibroblasts was inhibited by the cPLA2α inhibitors pyrrolidine-2 (IC50, 0.03 µM) and Wyeth-1 (IC50, 0.1 µM), implicating another C2 domain-containing group IV PLA2. cPLA2α-/- fibroblasts contain cPLA2β and cPLA2ζ but not cPLA2ϵ or cPLA2δ. Purified cPLA2ζ exhibited much higher lysophospholipase and PLA2 activity than cPLA2β and was potently inhibited by pyrrolidine-2 and Wyeth-1, which did not inhibit cPLA2β. In contrast to cPLA2β, cPLA2ζ expressed in Sf9 cells mediated A23187-induced arachidonic acid release, which was inhibited by pyrrolidine-2 and Wyeth-1. cPLA2ζ exhibits specific activity, inhibitor sensitivity, and low micromolar calcium dependence similar to cPLA2α and has been identified as the PLA2 responsible for calcium-induced fatty acid release and prostaglandin E2 production from cPLA2α-/- lung fibroblasts. In response to ionomycin, EGFP- cPLA2ζ translocated to ruffles and dynamic vesicular structures, whereas EGFP-cPLA2α translocated to the Golgi and endoplasmic reticulum, suggesting distinct mechanisms of regulation for the two enzymes. [ABSTRACT FROM AUTHOR]

Abstract: The Group IV phospholipase A2 family is comprised of six intracellular enzymes commonly called cytosolic phospholipase A2 (cPLA2) α, cPLA2β, cPLA2γ, cPLA2δ, cPLA2ε and cPLA2ζ. They are most homologous to phospholipase A and phospholipase B/lysophospholipases of filamentous fungi particularly in regions containing conserved residues involved in catalysis. However, a number of other serine acylhydrolases (patatin, Group VI PLA2s, Pseudomonas aeruginosa ExoU and NTE) contain the Ser/Asp catalytic dyad characteristic of Group IV PLA2s, and recent structural analysis of patatin has confirmed its structural similarity to cPLA2α. A characteristic of all these serine acylhydrolases is their ability to carry out multiple reactions to varying degrees (PLA2, PLA1, lysophospholipase and transacylase activities). cPLA2α, the most extensively studied Group IV PLA2, is widely expressed in mammalian cells and mediates the production of functionally diverse lipid products in response to extracellular stimuli. It has PLA2 and lysophospholipase activities and is the only PLA2 that has specificity for phospholipid substrates containing arachidonic acid. Because of its role in initiating agonist-induced release of arachidonic acid for the production of eicosanoids, cPLA2α activation is important in regulating normal and pathological processes in a variety of tissues. Current information available about the biochemical properties and tissue distribution of other Group IV PLA2s suggests they may have distinct mechanisms of regulation and functional roles. [Copyright &y& Elsevier]

In this study, we identify the principal splice variant of human cytosolic phospholipase A2β (cPLA2β) (also known as Group IVB cPLA2) present in cells. In human lung, spleen, and ovary and in a lung epithelial cell line (BEAS-2B), cPLA2β is expressed as a 100-kDa protein, not the 114-kDa form originally predicted. Using RNA interference, the 100-kDa protein in BEAS-2B cells was confirmed to be cPLA2β. BEAS-2B cells contain three different RNA splice variants of cPLA2β (β1, β2, and β3). cPLA2β is identical to the previously cloned cPLA2β, predicted to encode a 114-kDa protein. However, cPLA2β and cPLA2β3 splice variants are smaller and contain internal deletions in the catalytic domain. The 100-kDa cPLA2β in BEAS-2B cells is the translated product of cPLA2β3. cPLA2β3 exhibits calcium-dependent PLA2 activity against palmitoyl-arachidonyl-phosphatidylethanolamine and low level lysophospholipase activity but no activity against phosphatidylcholine. Unlike Group IVA cPLA2a, cPLA2β3 is constitutively bound to membrane in unstimulated cells, localizing to mitochondria and early endosomes. cPLA2β3 is widely expressed in tissues, suggesting that it has a generalized function at these unique sites. [ABSTRACT FROM AUTHOR]

In this paper we propose a fully automated offline handwriting recognition system that incorporates rule based segmentation, contour based feature extraction, neural network validation, a hybrid neural network classifier and a hamming neural network lexicon. The work is based on our earlier promising results in this area using heuristic segmentation and contour based feature extraction. The segmentation is done using many heuristic based set of rules in an iterative manner and finally followed by a neural network validation system. The extraction of feature is performed using both contour and structure based feature extraction algorithm. The classification is performed by a hybrid neural network that incorporates a hybrid combination of evolutionary algorithm and matrix based solution method. Finally a hamming neural network is used as a lexicon. A benchmark dataset from CEDAR has been used for training and testing. [ABSTRACT FROM AUTHOR]

Nanocrystals of CdO have been obtained by the decomposition of the cupferron complex in the presence of tri-n-octylphosphine oxide (TOPO) under solvothermal conditions. The precursor:TOPO ratio plays an important role in determining the size of the nanocrystals. The nanocrystals have been characterized by electron microscopy, absorption spectroscopy and fluorescence spectroscopy, besides X-ray diffraction. The CdO nanocrystals are single crystalline and show evidence for quantum confinement. CuO nanocrystals could also be prepared by the decomposition of the cupferronate under solvothermal conditions, the particle size being controlled by the initial precursor concentration. [Copyright &y& Elsevier]

The interface between water and an organic liquid has been exploited to prepare nanocrystals of CdS. The technique involves introducing an appropriate precursor of cadmium in the organic layer and the sulfiding reagent in the aqueous layer. The size distribution of the nanocrystals formed at the interface can be controlled by varying parameters such as the reactant concentration, temperature, viscosity of the medium, reaction time and the choice of the reagents. The CdS nanocrystals have been characterized by TEM, electronic absorption and emission spectroscopy. Nanocrystaline γ-Fe2O3 and ZnO can be prepared by taking cupferron complex of the metals in the organic layer and NaOH in the aqueous layer. [Copyright &y& Elsevier]

Hydrogel scaffolds have attracted much interest in the last few years for applications in the field of bone and cartilage tissue engineering. These scaffolds serve as a convenient three-dimensional structure on which cells can grow while sensing the native environment. Natural polymer-based hydrogels are an interesting choice for such purposes, but they lack the required mechanical properties. In contrast, composite hydrogels formed by biopolymers and short peptide hydrogelators possess mechanical characteristics suitable for osteogenesis. Here, we describe how combining the short peptide hydrogelator, Pyrene-Lysine-Cysteine (PyKC), with other biopolymers, can produce materials that are suitable for tissue engineering purposes. The presence of PyKC considerably enhances the strength and water content of the composite hydrogels, and confers thixotropic behavior. The hyaluronic acid-PyKC composite hydrogels were shown to be biocompatible, with the ability to support osteogenesis, since MC3 T3-E1 osteoblast progenitor cells grown on the materials displayed matrix calcification and osteogenic differentiation. The osteogenesis results and the injectability of these composite hydrogels hold promise for their future utilization in tissue engineering. [ABSTRACT FROM AUTHOR]

Aim: To investigate the potential of an ultrashort aromatic peptide hydrogelator integrated with hyaluronic acid (HA) to serve as a scaffold for bone regeneration. Materials and Methods: Fluorenylmethyloxycarbonyl‐diphenylalanine (FmocFF)/HA hydrogel was prepared and characterized using microscopy and rheology. Osteogenic differentiation of MC3T3‐E1 preosteoblasts was investigated using Alizarin red, alkaline phosphatase and calcium deposition assays. In vivo, 5‐mm‐diameter calvarial critical‐sized defects were prepared in 20 Sprague–Dawley rats and filled with either FmocFF/HA hydrogel, deproteinized bovine bone mineral, FmocFF/Alginate hydrogel or left unfilled. Eight weeks after implantation, histology and micro‐computed tomography analyses were performed. Immunohistochemistry was performed in six rats to assess the hydrogel's immunomodulatory effect. Results: A nanofibrous FmocFF/HA hydrogel with a high storage modulus of 46 KPa was prepared. It supported osteogenic differentiation of MC3T3‐E1 preosteoblasts and facilitated calcium deposition. In vivo, the hydrogel implantation resulted in approximately 93% bone restoration. It induced bone deposition not only around the margins, but also generated bony islets along the defect. Elongated M2 macrophages lining at the periosteum–hydrogel interface were observed 1 week after implantation. After 3 weeks, these macrophages were dispersed through the regenerating tissue surrounding the newly formed bone. Conclusions: FmocFF/HA hydrogel can serve as a cell‐free, biomimetic, immunomodulatory scaffold for bone regeneration. [ABSTRACT FROM AUTHOR]

Fever, headache, body aches, retro-orbital pain, haemorrhage and shock are well known manifestations of dengue infection. We report the case of a 4-y-old child with dengue who presented with meningo-encephalitis and subsequently developed myelitis, hepatitis, glomerulonephritis and bone marrow suppression. Complete recovery occurred within 3 weeks. [ABSTRACT FROM AUTHOR]

Peptide‐based supramolecular hydrogels are utilized as functional materials in tissue engineering, axonal regeneration, and controlled drug delivery. The Arg‐Gly‐Asp (RGD) ligand based supramolecular gels have immense potential in this respect, as this tripeptide is known to promote cell adhesion. Although several RGD‐based supramolecular hydrogels have been reported, most of them are devoid of adequate resilience and long‐range stability for in vitro cell culture. In a quest to improve the mechanical properties of these tripeptide‐based gels and their durability in cell culture media, the Fmoc‐RGD hydrogelator is non‐covalently functionalized with a biocompatible and biodegradable polymer, chitosan, resulting in a composite hydrogel with enhanced gelation rate, mechanical properties and cell media durability. Interestingly, both Fmoc‐RGD and Fmoc‐RGD/chitosan composite hydrogels exhibit thixotropic properties. The utilization of the Fmoc‐RGD/chitosan composite hydrogel as a scaffold for 2D and 3D cell cultures is demonstrated. The composite hydrogel is found to have notable antibacterial activity, which stems from the inherent antibacterial properties of chitosan. Furthermore, the composite hydrogels are able to produce ultra‐small, mono‐dispersed, silver nanoparticles (AgNPs) arranged on the fiber axis. Therefore, the authors' approach harnesses the attributes of both the supramolecular‐polymer (Fmoc‐RGD) and the covalent‐polymer (chitosan) component, resulting in a composite hydrogel with excellent potential. [ABSTRACT FROM AUTHOR]

The high demand for tissue engineering scaffolds capable of inducing bone regeneration using minimally invasive techniques prompts the need for the development of new biomaterials. Herein, we investigate the ability of Alginate incorporated with the fluorenylmethoxycarbonyl-diphenylalanine (FmocFF) peptide composite hydrogel to serve as a potential biomaterial for bone regeneration. We demonstrate that the incorporation of the self-assembling peptide, FmocFF, in sodium alginate leads to the production of a rigid, yet injectable, hydrogel without the addition of cross-linking agents. Scanning electron microscopy reveals a nanofibrous structure which mimics the natural bone extracellular matrix. The formed composite hydrogel exhibits thixotropic behavior and a high storage modulus of approximately 10 kPA, as observed in rheological measurements. The in vitro biocompatibility tests carried out with MC3T3-E1 preosteoblast cells demonstrate good cell viability and adhesion to the hydrogel fibers. This composite scaffold can induce osteogenic differentiation and facilitate calcium mineralization, as shown by Alizarin red staining, alkaline phosphatase activity and RT-PCR analysis. The high biocompatibility, excellent mechanical properties and similarity to the native extracellular matrix suggest the utilization of this hydrogel as a temporary three-dimensional cellular microenvironment promoting bone regeneration. [ABSTRACT FROM AUTHOR]

Background: Transcutaneous bilirubin is used as a screening tool before starting phototherapy in preterm newborn. However, there is conflicting evidence regarding its utility after starting phototherapy. There is also doubt regarding the best site of measurement. Objective: The objective was to analyze the association between transcutaneous bilirubin and serum bilirubin in Indian preterm newborns at different sites before, during, and after phototherapy. Methods: This prospective observational study was conducted in a tertiary care neonatal unit of eastern India from May 2019 to April 2020. Participants: The study participants were 90 preterm newborns admitted for phototherapy within the first 7 days of life. Intervention: Transcutaneous bilirubin was assessed by Draeger JM-105 at the covered areas of the sternum and forehead and serum bilirubin was assessed by the Diazo method within 30 min of each other. Bilirubin assessment was done before starting phototherapy and then repeated every 12 h till 24 h postphototherapy. Outcome: To determine the correlation and agreement between serum bilirubin and transcutaneous bilirubin in preterm newborns before, during and after phototherapy. Results: Median gestational age and mean birth weight of the enrolled infants were 33.5 weeks and 1920 g, respectively. Transcutaneous bilirubin from sternum demonstrated good correlation with serum bilirubin before (r = 0.856), during (r = 0.723 at 24 h), and after phototherapy (r = 0.801 at 24 h postphototherapy). Measurements from the forehead showed better correlation with serum bilirubin compared to the sternum (r = 0.865 before, 0.732 during, 0.814 after phototherapy). At both sites, correlation worsened with phototherapy but improved gradually in the postphototherapy period. Bland-Altman analysis revealed wide upper limit of agreement between transcutaneous bilirubin and serum bilirubin at both sites and all points of time, suggesting a transcutaneous device significantly overestimated serum bilirubin. Conclusion: There was good correlation but poor agreement between transcutaneous bilirubin and serum bilirubin in Indian preterm newborns irrespective of timing and site of measurement. [ABSTRACT FROM AUTHOR]

A correction to the article "Leishmania donovani Infection Enhances Lateral Mobility of Macrophage Membrane Protein Which Is Reversed by Liposomal Cholesterol" that was published in the previous issue, is presented.

The purpose of this study is to validate lung ultrasound score (LUS) for prediction of surfactant replacement therapy (SRT) in Indian infants of 27-336/7 weeks gestational age (GA). This prospective diagnostic accuracy study was conducted in a level 3 neonatal care unit in India. Consecutively born preterm infants with respiratory distress syndrome (RDS) were enrolled. Surfactant was administered if oxygen requirement exceeded > 30%. Baseline characteristics, respiratory parameters, and lung ultrasound images were recorded soon after admission and compared between surfactant and non-surfactant groups. Adjusted odds ratio (OR) and diagnostic accuracy of LUS were calculated for SRT. Among 78 infants with RDS included in the final analysis, 62 received surfactant (79.48%). Median time of performing lung ultrasound was 50 min of life in both groups. Median LUS in the anterior and posterior chest areas of either side as well as total LUS was significantly higher in the surfactant group. After adjusting for other confounders, LUS was found to be a significant predictor of SRT (adjusted OR (95%CI): 1.55 (1.15-2.087)). Diagnostic accuracy of LUS was determined by receiver operating characteristic (ROC) curve analysis (AUC (95% CI): 0.751 (0.64-0.842), p < 0.001). A cutoff score of ≥ 9 for LUS was considered optimal for SRT (sensitivity (95%CI): 70.97% (57.87-81.45), specificity (95%CI): 68.75% (41.48-87.87)).Conclusion: Lung ultrasound is a valid diagnostic tool for SRT in Indian setting with a cutoff score ≥ 9.Trial Registration: CTRI/2021/11/038269.What Is Known: • Surfactant requirement in preterm infants with RDS has been traditionally based on FiO2 criteria. • Lung ultrasound score can predict the need for surfactant although majority of the studies originated in developed countries.What Is New: • Lung ultrasound is a valid tool for surfactant replacement therapy even in developing countries like India. [ABSTRACT FROM AUTHOR]

Background: Twenty-five percent to 45% of COPD is caused by exposures other than active smoking. Secondhand tobacco smoke (SHS) has been suggested as an independent cause of COPD, based on its association with increased respiratory symptoms and a small decrease in lung function, but its impact on respiratory health and lung function after exposure cessation has not been explored.Research Question: What are the consequences of airline SHS exposure on respiratory health and lung function decades after cessation?Study Design and Methods: We performed a cohort study involving flight attendants because of their exposure to SHS that stopped > 20 years ago. We included subjects ≥ 50 years of age with > 1 year vs ≤ 1 year of airline SHS exposure (ie, exposed vs unexposed). Respiratory quality of life, as determined by the St. George's Respiratory Questionnaire (SGRQ), was the primary outcome for respiratory health. Key secondary outcomes included general quality of life (the Rand Corporation modification of the 36-item Short Form Health Survey Questionnaire; RAND-36), respiratory symptoms (COPD Assessment Test; CAT), and spirometry.Results: The study enrolled 183 SHS-exposed and 59 unexposed subjects. Exposed subjects were 66.7 years of age, and 90.7% were female. They were hired at 23.8 years of age, were exposed to airline SHS for 16.1 years, and stopped exposure 27.5 years before enrollment. Prior SHS exposure was associated with worsened SGRQ (6.7 units; 95% CI, 2.7-10.7; P = .001), RAND-36 physical and social function, and CAT vs unexposed subjects. SHS exposure did not affect prebronchodilator spirometry or obstruction, but was associated with lower postbronchodilator FEV1 and FEV1/FVC, total lung capacity, and diffusing capacity of the lungs for carbon monoxide in a subset of subjects. Former smoking and SHS exposure synergistically worsened SGRQ (β = 8.4; 95% CI, 0.4-16.4; P = .04). SHS exposure in people who never smoked replicated primary results and was associated with worsened SGRQ vs unexposed people (4.7 units; 95% CI, 0.7-7.0; P = .006).Interpretation: Almost three decades after exposure ended, airline SHS exposure is strongly and dose-dependently associated with worsened respiratory health, but less robustly associated with airflow abnormalities used to diagnose COPD. [ABSTRACT FROM AUTHOR]

A pyrene-containing phenylboronic acid (PBA) functionalized low-molecular-weight hydrogelator was synthesized with the aim to develop glucose-sensitive insulin release. The gelator showed the solvent imbibing ability in aqueous buffer solutions of pH values, ranging from 8-12, whereas the sodium salt of the gelator formed a hydrogel at physiological pH 7.4 with a minimum gelation concentration (MGC) of 5 mg mL−1. The aggregation behavior of this thermoreversible hydrogel was studied by using microscopic and spectroscopic techniques, including transmission electron microscopy, FTIR, UV/Vis, luminescence, and CD spectroscopy. These investigations revealed that hydrogen bonding, π-π stacking, and van der Waals interactions are the key factors for the self-assembled gelation. The diol-sensitive PBA part and the pyrene unit in the gelator were judiciously used in fluorimetric sensing of minute amounts of glucose at physiological pH. The morphological change of the gel due to addition of glucose was investigated by scanning electron microscopy, which denoted the glucose-responsive swelling of the hydrogel. A rheological study indicated the loss of the rigidity of the native gel in the presence of glucose. Hence, the glucose-induced swelling of the hydrogel was exploited in the controlled release of insulin from the hydrogel. The insulin-loaded hydrogel showed thixotropic self-recovery property, which hoisted it as an injectable soft composite. Encouragingly, the gelator was found to be compatible with HeLa cells. [ABSTRACT FROM AUTHOR]

We demonstrate the potential of a converging–diverging microchannel to split a stream of nanoparticles towards the interfacial region of the dispersed and the carrier phases, introduced through the middle inlet and through the remaining two inlets respectively, while maintaining a low Reynolds number limit (＜10) for the flow of both phases. In addition to the splitting of passive tracer particles, such as polystyrene beads as used herein, the present setup has the potential to be utilized for a controlled reaction and thereby the separation of products towards an intended location, as observed from the experimentation with silver-nanoparticles and hydrogen–peroxide solution. Moreover, the microscale dimension of the channel allows controlled deposition of the reaction product over the bottom surface of the channel, allowing the possibility of bottom-up fabrication of microscale features. We unveil the underlying hydrodynamics that lead to such behaviours through numerical simulations, which are consistent with the experimental observations. The phenomenological features are found to be guided by the splitting of the intrinsic streamlines conforming to the flow geometry under consideration. [ABSTRACT FROM AUTHOR]

We show that Leishmania donovani-infected macrophages (MΦs) are capable of stimulating MHC class II (MHC-II)-restricted T cells at 6 h of infection. At 48 h, infected MΦs (I-MΦs) failed to stimulate MHC-II-restricted T cells but not MHC class I-restricted ones, in contrast to normal MΦs. Such I-MΦs could stimulate T cells at a higher Ag concentration, indicating that general Ag processing and trafficking of peptide-MHC-II complexes are not defective. Analysis of the kinetic parameters, like "kon" and "koff," showed that peptide-MHC-II complex formation is compromised in I-MΦs compared with normal MΦs. This indicates interference in loading of the cognate peptide to MHC-II, which may be due to the presence of a noncognate molecule. This notion received support from the finding that exposure of I-MΦs to low pH or treatment with 2-(1-adamantyl)-ethanol, a molecule that favors peptide exchange, led to T cell activation. When treated with 2-(1-adamantyl)-ethanol, splenocytes from 8 wk-infected BALB/c mice showed significantly higher antileishmanial T cell expansion in vitro compared with untreated controls. Hence, it is tempting to speculate that high, but not low, concentrations of cognate peptide may favor peptide exchange in I-MΦs, leading to expansion of the antileishmanial T cell repertoire. The results suggest that a high Ag dose may overcome compromised T cell responses in visceral leishmaniasis, and this has an important implication in therapeutic vaccine design. [ABSTRACT FROM AUTHOR]

Perturbation of calcium signaling that occurs during cell injury and disease, promotes cell death. In mouse lung fibro-blasts A23187 triggered mitochondrial permeability transition pore (MPTP) formation, lactate dehydrogenase (LDH) release, and necrotic cell death that were blocked by cyclosporin A (CsA) and EGTA. LDH release temporally correlated with arachidonic acid release but did not involve cytosolic phospholipase A2α (cPLA2α) or calcium-independent PLA2. Surprisingly, release of arachidonic acid and LDH from cPLA2α-deficient fibroblasts was inhibited by the cPLA2α inhibitor pyrrophenone, and another serine hydrolase inhibitor KT195, by preventing mitochondrial calcium uptake. Inhibitors of calcium/calmodulin-dependent protein kinase II, a mitochondrial Ca2+ uniporter (MCU) regulator, also prevented MPTP formation and arachidonic acid release induced by A23187 and H2O2. Pyrrophenone blocked MCU-mediated mitochondrial calcium uptake in per-meabilized fibroblasts but not in isolated mitochondria. Unlike pyrrophenone, the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol and CsA blocked cell death and arachidonic acid release not by preventing mitochondrial calcium uptake but by inhibiting MPTP formation. In fibroblasts stimulated with thapsi-gargin, which induces MPTP formation by a direct effect on mitochondria, LDH and arachidonic acid release were blocked by CsA and 1-oleoyl-2-acetyl-sn-glycerol but not by pyrrophenone or EGTA. Therefore serine hydrolase inhibitors prevent necrotic cell death by blocking mitochondrial calcium uptake but not the enzyme releasing fatty acids that occurs by a novel pathway during MPTP formation. This work reveals the potential for development of small molecule cell-permeable serine hydrolase inhibitors that block MCU-mediated mitochondrial calcium overload, MPTP formation, and necrotic cell death. [ABSTRACT FROM AUTHOR]

Objectives: This study compared the risk of hypoglycemia within 72 h of life in infants with and without exposure to antenatal dexamethasone in the late preterm period (34-366/7 week's gestational age).Methods: This prospective cohort study was conducted in a tertiary care neonatal unit of Eastern India from May 2021 to November 2021. Babies in the exposed group received at least one dose of antenatal dexamethasone in the late preterm period between 7 days before delivery and birth. 'Complete course' of antenatal steroid was defined as four doses of injection dexamethasone at 12 h intervals and <4 doses were considered as 'Partial course'. Primary outcome was incidence of hypoglycemia within 72 h of life, defined as whole blood glucose <45 mg/dl.Results: Total 298 infants (98 in control, 134 in partial and 66 in complete group) were assessed for final outcome. No significant difference in outcomes were seen in the exposed group compared to unexposed group. However, incidence of hypoglycemia within 72 h (complete vs. partial p= 0.008, complete vs. control p=0.005) and 12 h of life (complete vs. partial p=0.013, complete vs. control p=0.013) was significantly less in complete steroid group. Logistic regression analysis revealed complete course of antenatal corticosteroid significantly decreased the risk of hypoglycemia [adjusted odds ratio, 95% confidence interval (CI) 0.15 (0.03-0.69), p=0.015]. Number needed to be exposed for one additional benefit was 7 (95% CI, 6.35-22.14).Conclusion: Complete course of dexamethasone administered to mothers at risk of late preterm delivery reduces risk of neonatal hypoglycemia within 72 h of life. [ABSTRACT FROM AUTHOR]

Abstract: Herein, we report the successful inclusion of 2D allotrope of carbon, graphene oxide (GO) in cetyltrimethylammonium bromide (CTAB)/isooctane/n-hexanol/water reverse micelle without compromising the stability of water-in-oil (w/o) microemulsion. This newly developed self-assembled nanocomposites act as proficient host for surface-active enzymes, lipase, horseradish peroxidase (HRP), and soybean peroxidase (SBP). Lipase activity within GO-doped CTAB reverse micelles remarkably improved by 3.8-fold compared to that was observed in only CTAB reverse micelle (second-order rate constant, k 2 =433±7cm3 g−1 s−1). In case of GO-doped CTAB reverse micelle, the observed enzyme activity (k 2 =1653±11cm3 g−1 s−1) is till date the highest ever activity of lipase in CTAB w/o microemulsions. In case of HRP and SBP, the catalytic efficiency maximally increased up to 2.6-fold and 2.3-fold, respectively. Electrostatic attraction between cationic head group of CTAB and anionic surface of GO as well as intrinsic amphiphilic character of GO possibly resulted in the confinement of this 2D nanosheet at the interface of reverse micelles. Integration of GO at the interface augmented the interfacial space in vicinity of surface-active enzyme. This enlarged interface might have accommodated higher amount of substrate and lipase with flexibility in its conformation resulting in marked improvement in the enzyme activity. Interfacial localization of GO was established by fluorescence spectroscopy. In addition, change in secondary structure of lipase in presence of 2D carbon allotrope was substantiated by circular dichroism spectroscopy. [Copyright &y& Elsevier]

Abstract: Approximately 1.5–2.5 μm thick nanocomposite coatings of TiAlCrYN were deposited using a four-cathode reactive unbalanced pulsed direct current magnetron sputtering system from the sputtering of Ti, Al, Cr, and Y targets in Ar + N2 plasma. The TiAlCrYN nanocomposite coatings were deposited on various substrates such as high speed steel (HSS) drill bits, mild steel and silicon. TiAlCrYN coatings with almost similar mechanical properties but with different Ti, Al, Cr and Y contents were prepared to study their thermal stability and machining performance. The structural and mechanical properties of the coatings were characterized using X-ray diffraction and nanoindentation technique, respectively. The elemental composition, bonding structure, surface morphology and cross-sectional data were studied using energy-dispersive X-ray analysis, X-ray photoelectron spectroscopy and field-emission scanning electron microscopy, respectively. Nanoscratch tests were performed to determine the adhesive strength of the coatings. The corrosion behavior of TiAlCrYN nanocomposite coatings on mild steel substrate was studied using potentiodynamic polarization in a 3.5% NaCl solution. Micro-Raman spectroscopy was used to characterize the structural changes as a result of heating of the nanocomposite coatings in air (600–1000 °C). TiAlCrYN coatings prepared at 17 at.% Ti, 13 at.% Al, 21 at.% Cr and 1 at.% Y exhibited thermal stability as high as 900 °C in air (denoted as Sample 3). For the performance evaluation, the TiAlCrYN coated HSS drill bits were tested under accelerated machining conditions. With a drill speed of 800 rpm and a feed rate of 0.08 mm/rev the TiAlCrYN coated HSS drill bits (Sample 3) averaged 657 holes, while drilling a 12 mm thick 304 stainless steel plate under dry conditions, before failure. Whereas, the uncoated drill bits failed after drilling 50 holes under the same machining conditions. Results indicated that for the HSS drill bits coated with TiAlCrYN, the tool life increased by a factor of more than 12. [Copyright &y& Elsevier]

In this paper we investigate a hybrid model based on the Discrete Gradient method and an evolutionary strategy for determining the weights in a feed forward artificial neural network. Also we discuss different variants for hybrid models using the Discrete Gradient method and an evolutionary strategy for determining the weights in a feed forward artificial neural network. The Discrete Gradient method has the advantage of being able to jump over many local minima and find very deep local minima. However, earlier research has shown that a good starting point for the discrete gradient method can improve the quality of the solution point. Evolutionary algorithms are best suited for global optimisation problems. Nevertheless they are cursed with longer training times and often unsuitable for real world application. For optimisation problems such as weight optimisation for ANNs in real world applications the dimensions are large and time complexity is critical. Hence the idea of a hybrid model can be a suitable option. In this paper we propose different fusion strategies for hybrid models combining the evolutionary strategy with the discrete gradient method to obtain an optimal solution much quicker. Three different fusion strategies are discussed: a linear hybrid model, an iterative hybrid model and a restricted local search hybrid model. Comparative results on a range of standard datasets are provided for different fusion hybrid models. [ABSTRACT FROM AUTHOR]

Phagocytosis of non-opsonized microorganisms by macrophages initiates innate immune responses for host defense against infection. Cytosolic phospholipase A2 is activated during phagocytosis, releasing arachidonic acid for production of eicosanoids, which initiate acute inflammation. Our objective was to identify pattern recognition receptors that stimulate arachidonic acid release and cyclooxygenase 2 (COX2) expression in macrophages by pathogenic yeast and yeast cell walls. Zymosan- and Candida albicans-stimulated arachidonic acid release from resident mouse peritoneal macrophages was blocked by soluble glucan phosphate. In RAW264.7 cells arachidonic acid release, COX2 expression, and prostaglandin production were enhanced by overexpressing the β-glucan receptor, dectin-1, but not dectin-1 lacking the cytoplasmic tail. Pure particulate (1, 3)-β-D-glucan stimulated arachidonic acid release and COX2 expression, which were augmented in a Toll-like receptor 2 (TLR2)-dependent manner by macrophage-activating lipopeptide-2. However, arachidonic acid release and leukotriene C4 production stimulated by zymosan and C. albicans were TLR2-independent, whereas COX2 expression and prostaglandin production were partially blunted in TLR2-/- macrophages. Inhibition of Syk tyrosine kinase blocked arachidonic acid release and COX2 expression in response to zymosan, C. albicans, and particulate (1, 3)-β-D-glucan. The results suggest that cytosolic phospholipase A2 activation triggered by the β-glucan component of yeast is dependent on the immunoreceptor tyrosine-based activation motif-like domain of dectin-1 and activation of Syk kinase, whereas both TLR2 and Syk kinase regulate COX2 expression. [ABSTRACT FROM AUTHOR]