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Hydroxyapatite (HAp) supported nickel catalysts were synthesised via simple urea precipitation method with various nickel loadings ranging from 5 to 20 wt% and tested in vapour phase hydrogenation of levulinic acid (LA) under ambient pressure. The as-prepared catalysts were systematically characterized by using X-ray diffraction, UV-DRS, HR-TEM, SEM, BET surface area, TPR and TPD-CO2 techniques. The active nickel surface area and the Ni dispersion over the HAp support were measured by using H2 chemisorption method. The XRD results confirmed that the nickel oxide particles were well dispersed over HAp support at lower loadings and NiO crystallites were formed at higher loadings. The HR-TEM images revealed that ultra small (2.49 ± 0.4 nm) and homogenously distributed nickel nanoparticles are formed over 5 wt% NiHAp catalyst. Moreover, UV-DRS analysis is also confirmed the similar phenomena. The H2-TPR analysis revealed that the presence of strong interaction between nickel particles and hydroxyapatite support was observed. Among several HAp supported Ni catalysts tested in this study, we found that 5 wt% NiHAp catalyst is the most active and selective due to the presence of high number of active surface Ni particles over HAp support and this was confirmed by the H2 chemisorption analysis and HR-TEM.

Hospital-acquired pneumonia (HAP) is defined as an infection in patients admitted in hospital for more than 48hours, and ventilator associated pneumonia (VAP) can be defined as infection occurring in patients admitted in ICU after 48hrs endotracheal intubation and mechanical ventilation. VAP has a mean of 7.3/1000 ventilator days for medical ICU patients and 13.2/1000 ventilator days for surgical ICU patients. The crude mortality rates for HAP are approximately 10% and are higher for VAP, ranging from 20% to 60%. The culture of endotracheal (ET) aspirates will help know the etiological agent and formulate the antibiotic policy for early treatment. To isolate the bacterial pathogens of ET secretions from patients with VAP and know their antibiotic susceptibility pattern. In the present study, out of 102 endotracheal secretions from cases of VAP, 88 samples (86.27%) were culture positive, and the remaining 14 samples (13.73%) were culture negative. Out of the 88 positive cultures, 62 samples (60.78%) showed growth of single isolates, and 26 samples (25.49%) showed multiple isolates. Out of the 114 isolates, 18 isolates (15.8%) were gram positive organisms, and 96 isolates (84.2%) were gram negative organisms. Of the gram positive isolates, the predominant organism was Methicillin resistant (MRSA) (55.56%), followed by Methicillin sensitive (MSSA) (22.22%) and (22.22%). Out of the gram negative isolates, the predominant organism was (36.46%), followed by Acinetobacter spp (25%), (23.96%), (12.5%), (1.04%), and Proteus mirabilis (1.04%). In the present study, Gram positives isolates showed the highest susceptibility to vancomycin and linezolid (100%), and gram negative isolates showed the highest susceptibility to polymyxin B (100%) and meropenem (47.92%). The study gives insight into the bacterial pathogens and their antibiotic susceptibility patterns of isolates from endotracheal secretions of mechanically ventilated patients to prevent the mortality and morbidity of mechanical ventilation and VAP, helping in formulating an antibiotic policy for appropriate empirical therapy.

Graphical abstract, Highlights • H2S derived from CSE/CBS inhibits inflammation and calcification of valvular interstitial cells. • H2S releasing molecules inhibits inflammation and calcification of valvular interstitial cells. • H2S inhibits inflammation and calcification in aortic valve of apolipoprotein E deficient mice. • H2S suppresses nuclear translocation of NF-κB and subsequent expression of IL-1β and TNF-α. • Activation of Runx2, its nuclear translocation is mediated by NF-κB in calcifying conditions. • Inflammation and calcification are connected via master transcription factors, NF-κB and Runx2., Introduction Hydrogen sulfide (H2S) was revealed to inhibit aortic valve calcification and inflammation was implicated in the pathogenesis of calcific aortic valve disease (CAVD). Objectives We investigate whether H2S inhibits mineralization via abolishing inflammation. Methods and results Expression of pro-inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) were increased in patients with CAVD and in calcified aortic valve of ApoE-/- mice. Administration of H22S releasing donor (4-methoxyphenyl piperidinylphosphinodithioc acid (AP72)) exhibited inhibition on both calcification and inflammation in aortic valve of apolipoprotein E knockout mice (ApoE-/-) mice is reflected by lowering IL-1β and TNF-α levels. Accordingly, AP72 prevented the accumulation of extracellular calcium deposition and decreased nuclear translocation of nuclear factor-κB (NF-κB) in human valvular interstitial cells (VIC). This was also accompanied by reduced cytokine response. Double-silencing of endogenous H2S producing enzymes, Cystathionine gamma-lyase (CSE) and Cystathionine beta-synthase (CBS) in VIC exerted enhanced mineralization and higher levels of IL-1β and TNF-α. Importantly, silencing NF-κB gene or its pharmacological inhibition prevented nuclear translocation of runt-related transcription factor 2 (Runx2) and subsequently the calcification of human VIC. Increased levels of NF-κB and Runx2 and their nuclear accumulation occurred in ApoE-/- mice with a high-fat diet. Administration of AP72 decreased the expression of NF-κB and prevented its nuclear translocation in VIC of ApoE-/- mice on a high-fat diet, and that was accompanied by a lowered pro-inflammatory cytokine level. Similarly, activation of Runx2 did not occur in VIC of ApoE-/- mice treated with H2S donor. Employing Stimulated Emission Depletion (STED) nanoscopy, a strong colocalization of NF-κB and Runx2 was detected during the progression of valvular calcification. Conclusions Hydrogen sulfide inhibits inflammation and calcification of aortic valve. Our study suggests that the regulation of Runx2 by hydrogen sulfide (CSE/CBS) occurs via NF-κB establishing a link between inflammation and mineralization in vascular calcification.

The lysis of red blood cells was shown to occur in human ruptured atherosclerotic lesions and intraventricular hemorrhage (IVH) of the brain. Liberated cell-free hemoglobin was found to undergo oxidation in both pathologies. We hypothesize that hemoglobin-derived peptides are generated during hemoglobin oxidation both in complicated atherosclerotic lesions and IVH of the brain, triggering endothelial cell dysfunction. Oxidized hemoglobin and its products were followed with spectrophotometry, LC–MS/MS analysis and detection of the cross-linking of globin chains in complicated atherosclerotic lesions of the human carotid artery and the hemorrhaged cerebrospinal liquid of preterm infants. The vascular pathophysiologic role of oxidized hemoglobin and the resultant peptides was assessed by measuring endothelial integrity, the activation of endothelial cells and the induction of proinflammatory genes. Peptide fragments of hemoglobin (VNVDEVGGEALGRLLVVYPWTQR, LLVVYPWTQR, MFLSFPTTK, VGAHAGEYGAELERMFLSFPTTK, and FLASVSTVLTSKYR) were identified in ruptured atherosclerotic lesions and in IVH of the human brain. Fragments resulting from the oxidation of hemoglobin were accompanied by the accumulation of ferryl hemoglobin. Similar to complicated atherosclerotic lesions of the human carotid artery, a high level of oxidized and cross-linked hemoglobin was observed in the cerebrospinal fluid after IVH. Haptoglobin inhibited hemoglobin fragmentation provoked by peroxide. The resultant peptides failed to bind haptoglobin or albumin. Peptides derived from hemoglobin oxidation and ferryl hemoglobin induced intercellular gap formation, decreased junctional resistance in the endothelium, and enhanced monocyte adhesion to endothelial cells. Enhanced expression of TNF and the activation of NLRP3 and CASP1 followed by the increased generation of IL-1β and nuclear translocation of the NF-κβ transcription factor occurred in response to hemoglobin-derived peptides, and ferryl hemoglobin in endothelium was upregulated in both pathologies. We conclude that the oxidation of hemoglobin in complicated atherosclerotic lesions and intraventricular hemorrhage of the brain generates peptide fragments and ferryl hemoglobin with the potential to trigger endothelial cell dysfunction., Generation of peptide fragments by oxidation of hemoglobin to ferryl hemoglobin occurs in ruptured atherosclerotic lesion in human and in intraventricular hemorrhage of brain in preterm infants. Peptide fragments of hemoglobin provoke intercellular gap formation and enhance monocyte adhesion to endothelial cell. Activation of endothelium via NF-κβ leads to TNF and IL-1β production, induction of NLRP3 and CASP1.

Key points Cystic fibrosis transmembrane conductance regulator (CFTR) is an important ion channel in epithelial cells. Its malfunction has several serious consequences, like developing or aggravating acute pancreatitis (AP). Here, we investigated the localization and expression of CFTR during cerulein-induced AP in mice and determined the effects of CFTR corrector (VX-661) and potentiator (VX-770) on disease severity. CFTR mRNA expression was significantly increased, and mislocalization of CFTR protein was observed in AP compared to the control group. Interestingly, pre-treatment of AP mice with VX-661 + VX-770 significantly reduced the extent of pancreatic tissue damage by 20-30%. In vitro administration of VX-661 + VX-770 significantly increased the fluid secretion of ducts derived from AP animals. Based on our results, the utilization of CFTR correctors and potentiators should be further investigated in AP. Abstract Cystic fibrosis transmembrane conductance regulator (CFTR) has essential role in maintaining pancreatic ductal function. Impaired CFTR function can trigger acute pancreatitis (AP) and exacerbate disease severity. We aimed to investigate the localization and expression of CFTR during AP, and determined the effects of CFTR corrector (VX-661) and potentiator (VX-770) on disease severity. AP was induced in FVB/n mice by 6-10 hourly intraperitoneal injections of 50μg/kg cerulein. Some mice were pre-treated with 5-6 daily injections of 2mg/kg VX-661+VX-770. Control animals were administered physiological saline instead of cerulein and DMSO instead of VX compounds. AP severity was determined by measuring laboratory and histological parameters; CFTR and CK19 expressions were measured. Activity of ion transporters was followed by intracellular pH or fluid secretion measurement of isolated pancreatic intra-/interlobular ducts. Cerulein-induced AP severity was greatest between 12-24h. CFTR mRNA expression was significantly increased 24h after AP induction. Immunohistochemistry demonstrated disturbed staining morphology of CFTR and CK19 proteins in AP. Mislocalization of CFTR protein was observed from 6h, while expression increased at 24h compared to control. Ductal HCO3 - transport activity was significantly increased 6h after AP induction. AP mice pre-treatment with VX-661+VX-770 significantly reduced the extent of tissue damage by about 20-30%, but other parameters were unchanged. Interestingly, VX-661+VX-770 in vitro administration significantly increased the fluid secretion of ducts derived from AP animals. This study described the course of the CFTR expression and mislocalization in cerulein-induced AP. Our results suggest that the beneficial effects of CFTR correctors and potentiators should be further investigated in AP. This article is protected by copyright. All rights reserved.

The reactivity of 2-ethoxy ethanol with OH radicals was experimentally measured in the temperature range of 278-363 K using the pulsed laser photolysis-laser-induced fluorescence (PLP-LIF) technique. The rate coefficient at room temperature was measured to be (1.14 ± 0.03) × 10-11 cm3 molecule-1 s-1, and the Arrhenius expression was derived to be kexpt278-363K = (1.61 ± 0.35) × 10-13 exp{(1256 ± 236)/T} cm3 molecule-1 s-1. Computational calculations were performed to compute the kinetics of the titled reaction in the temperature range of 200-400 K using advanced methods incorporated with tunneling correction at the CCSD(T)/aug-cc-pVTZ//M06-2X/6-31+G(d,p) level of theory. The Arrhenius expression derived from the computationally calculated rate coefficients is ktheo200-400K = (1.59 ± 0.35) × 10-13exp{(1389 ± 62)/T} cm3 molecule-1 s-1. The feasibility of each reaction pathway was also determined using the calculated thermochemical parameters. Atmospheric implication parameters such as cumulative atmospheric lifetime and photochemical ozone creation potential were calculated and are discussed in this paper.

The aim of the present paper is to analyse the transient Couette nanofluid flow of ethylene glycol (EG)-ferrous oxide (Fe3O4) between two parallel plates in the presence of pulsative pressure gradi...

Utilization of biomass into liquid fuels and chemicals will be reduce the dependency on fossil-based resources and CO2 emissions. In this work, we report a series of copper (loadings 5−20 wt.%) supported on calcined Mg9Al2.7-Ga2.3O2 (Ga2.3-HT) catalysts were prepared by a wetness impregnation method and their catalytic performance was investigated for the production of 1,2-propanediol from glycerol in a vapor phase. The physicochemical properties of the these catalysts were characterized by X-ray diffraction (XRD), N2 adsorption (BET), Transmission electron microscopy (TEM), Scanning electron microscopy (SEM), Elemental mapping, UV–vis diffused reflectance spectroscopy (UV-DRS), CO2-Temperature programmed desorption (CO2-TPD), N2O chemisorption and temperature programmed reduction (TPR) analysis. These results demonstrated that Ga promotional effects observed to be significant over the Ga2.3-HT support and that influenced the final Cu based catalysts. Moreover, Cu functioning is found to be a vital role for achieved high catalytic activity in glycerol hydrogenolysis. Lower Cu loading is a more active and selective to the 1,2-PrDs production due to highly dispersed particles, and distributed homogeneously along with enough number of basic sites and acido-basic sites. The catalytic activity of calcined 5CuO/Ga2.3-HT was systematically investigated under varying reaction parameters including copper loading, various Mg/Al/Ga ratios, reaction temperature, hydrogen flow rate, glycerol concentration and weight hourly space velocity to derive the optimum conditions for the reaction. The catalyst stability, reusability and structure-activity correlation were also elucidated.

Magnesium (Mg) and its alloys have been widely explored as a potential biodegradable implant material. However, the fast degradation of Mg-based alloys under physiological environment has hindered their widespread use for implant applications till date. The present review focuses on in vitro and in vivo degradation of biodegradable Mg alloys, and preventive measures for biomedical applications. Initially, the corrosion assessment approaches to predict the degradation behavior of Mg alloys are discussed along with the measures to control rapid corrosion. Furthermore, this review attempts to explore the correlation between in vitro and in vivo corrosion behavior of different Mg alloys. It was found that the corrosion depends on experimental conditions, materials and the results of different assessment procedures hardly matches with each other. It has been demonstrated the corrosion rate of magnesium can be tailored by alloying elements, surface treatments and heat treatments. Various researches also studied different biocompatible coatings such as dicalcium phosphate dihydrate (DCPD), β-tricalcium phosphate (β-TCP), hydroxyapatite (HA), polycaprolactone (PCL), polylactic acid (PLA), and so on, on Mg alloys to suppress rapid degradation and examine their influence on new bone regeneration as well. This review shows the need for a standard method of corrosion assessment to predict the in vivo corrosion rate based on in vitro data, and thus reducing the in vivo experimentation.

The Cl/OH initiated temperature dependent photo-oxidative reaction kinetics of methyl butyrate (MB) were examined using a relative rate (RR) technique. Gas chromatography with flame ionization and mass spectrometric detection were used to monitor the concentration of the reactants and to identify the products. The temperature dependent kinetics of MB with Cl atoms were measured with respect to the reaction of Cl with C2H 6 and C2H4. The temperature dependent kinetics for the reaction of MB with OH radicals were measured using n- propanol and iso -propanol as references. The obtained rate coefficients for the Cl and OH reactions with MB are, k Cl(Expt) (T) = [(7.76 ± 0.47) × 10 −11] exp [(10.31 ± 0.20)/T] cm3 molecule−1 s−1 and k OH(Expt) (T) = [(4.32 ± 0.21) × 10 −12] exp [-(25.26 ± 0.39)/T] cm3 molecule−1 s−1 respectively. Dual level direct dynamics were used to perform the computational calculations to further elucidate the mechanisms over the studied temperature range. The rate coefficients for H-abstraction reactions were computed using Canonical Variational Transition State Theory with Small Curvature Tunneling (CVT/SCT) with Interpolated Single Point Energies (ISPE) method. The rate coefficients over the studied temperature range yielded the Arrhenius equations: k Cl(Theory) (200–400 K) = [(4.05 ± 0.54) × 10–11] exp [-(2.80 ± 0.11)/T] cm3 molecule−1 s−1 and k OH(Theory) (200–400 K) = [(1.96 ± 0.68) × 10 -11] exp [-(384 ± 38)/T] cm3 molecule −1 s −1. Possible degradation mechanisms for the reactions are proposed based on the observed products. Thermo-chemical parameters, ozone formation potential, branching ratios, and the atmospheric lifetime of MB are calculated to understand the fate of MB in the atmosphere.

Cryopreservation is a widely-used efficient means of long-term sperm preservation. However, unlike other types of semen, cryopreserved boar semen has reduced fertility and the efforts continue to optimize post-thawing sperm recovery. In this study, we evaluated the effects of various washing solutions (Hulsen solution, labmade DPBS and commercial DPBS) on post-thawing porcine sperm kinematics (CASA system), viability (SYBR-14/PI) and acrosome integrity (PSA/FITC). We also examined the effect of washing-centrifugation on frozen-thawed semen kinematics. The results indicate that type of washing solution and post-thawing centrifugation alters parameters linked to sperm quality (total motility, progressive motility, viability and acrosome integrity). Significantly higher (p < 0.05) motility and progressive motility were obtained when cryopreserved semen was processed with Hulsen solution. The postthaw percentage of live and intact acrosomal sperm was significantly higher in group 1 (Hulsen solution) as compared to other groups. Following thawing-centrifugation, the results showed significantly higher motility and progressive motility in group 1 than other groups. However, the latter two DPBS groups did not differ statistically. Taken together, Frozen-thawed spermatozoa motility, acrosome integrity and viability can be affected by the type of washing solution used. Moreover, centrifugation of frozenthawed semen has an unfavorable effect on total motility and progressive motility.

Gas chromatography (GC) is a frequently used analytical method for the determination of permanent and organic air components. The analysis usually needs two different columns in practice. The molecular sieve stationary phase can separate oxygen, nitrogen and carbon monoxide, but irreversibly adsorbs carbon dioxide and water. Porapak type columns are applicable for the measurement of carbon dioxide, however oxygen, argon, nitrogen and carbon monoxide are co-eluted. Usually these two types of columns are used in parallel for the determination. Carboxen stationary phase can separate carbon monoxide and carbon dioxide, but argon, oxygen and nitrogen are co-eluted. Thermal conductivity detector (TCD) and flame ionization detector (FID) are used commonly together for the determination of the separated components. TCD is applied for permanent gas analysis whereas FID – combined with a methanizer – is used for the detection of carbon monoxide, carbon dioxide and light hydrocarbons. Mass spectrometer (MS) is also a potential detector, because the properly chosen fragment ions can increase the selectivity.We developed a method for the determination of air components, using only one column and one detector. This method is suitable for the measurements by combining the advantages of the carboxen column with mass spectrometry. The validation parameters of the method were in the acceptable interval, so this method is able to determine the air components. The application of this technique to the analysis of cave air provided valuable information to the exploration of the Molnár János cave system.

Polyaryletherketones (PAEK) have been hitherto the most promising high-performance semicrystalline thermoplastic polymers (HPPs) for several biomedical applications. These polymers make a competent replacement to implantable metals due to their biocompatibility, osteointegration properties, substantial bond strength, pliability, radiolucency and a comparable bone-like flexural modulus. Lately, additive manufacturing (AM) of customized 3D-printed patient-specific implants (PSI) using rapid prototyping techniques has been used for several surgical and medical implantations. Also, rapid technological progresses viz., fused deposition modelling and selective laser sintering in consort with enhanced imaging know-hows have streamlined the critical glitches of conventional HPPs processability with directing them to manufacture medically proficient 3D-PSI. Thus, PAEK and its polymers could not only be tailored into end-use implantable medical devices but also fit into newer AM technology-mediated biomedical arenas for other unexplored HPPs. This review summarizes the till date research on 3D-printed PAEK implant technology and its potential possibilities for their modernization and expansion in diverse musculoskeletal and soft tissue applications.

Magnesium (Mg) alloys are attractive biodegradable metal used for medical implant applications. In the present investigation, as-cast and as-rolled Mg–5Zn–0.5Zr alloys were studied for microstructural, mechanical, corrosion behaviour and in vitro biocompatibility. The microstructural changes due to hot rolling strongly influenced the micro-hardness, elastic modulus and corrosion behaviour of the alloy. The micro-hardness of the alloy increased from 66 ± 5 HV in as-cast condition to 84 ± 3 HV after rolling. The corrosion resistance of the alloy decreased after rolling whereas both as-cast and as-rolled alloys showed adequate biocompatibility with mouse osteoblast precursor cell line (MC3T3-E1). In summary, the alloy has potential for customized degradable implant applications and the degradation behaviour depends on the processing route.

Background:: Chitosan nanoparticles have been extensively studied and used due to their well-recognized applicability in various fields. Chitosan, a natural polysaccharide polymer, is extensively used in pharmaceuticals to deliver a wide variety of therapeutic agents. Chitosan is a biocompatible and biodegradable mucoadhesive polymer that has been extensively used in the preparation of multi particles, particularly nano- and microparticles. Objective:: The main aim of the present study was to optimize the conditions for the preparation of chitosan nanoparticles to get optimal particle size, with optimal zeta potential and narrow polydispersity index and anti-bacterial activity. Methods:: Include the ionic gelation technique for chitosan nanoparticle preparation. The influence of formulation parameters and process parameters on the chitosan nanoparticles were investigated. Besides, the suspension stability of the prepared nanoparticles was also assessed on storage at 4°C. Results: The formulation and process parameters showed a significant effect on the physicochemical and morphological characteristics of the chitosan nanoparticles. The chitosan nanoparticles prepared under optimum conditions (chitosan concentration of 0.5% w/v, CS: TPP mass ratio of 1:3, initial pH of chitosan solution of 4.5, stirred at 750 rpm for 30 min) had shown a mean particle size of ~326.8±15 nm, zeta potential of +28.2 ± 0.5 mV, and PDI of 0.21 ± 0.02. The encapsulation of the clarithromycin slightly increased the polydispersity index, but the zeta potential of the unloaded nanoparticles was not affected while the particle size increased. Under optimum conditions, clarithromycin encapsulation efficiency into nanoparticles was found to be 70%. Additionally, chitosan- tripolyphosphate nanoparticles were shown to be stable for a minimum of fifteen days in deionized water at 4°C. Conclusion:: The current study concludes the optimal conditions to formulate the chitosan nanoparticles with optimal physicochemical characteristics.

This article is the first to demonstrate the application of dynamical U(2) Lie algebras to model a vibrational Hamiltonian of naphthalene (C10H8), a prototype polycyclic aromatic hydrocarbon molecu...

Sterilization of ultra-high molecular weight polyethylene (UHMWPE) based composites used for acetabular cup liner via UV or gamma-irradiation before surgery is inevitable. Thus, understanding the alteration of mechanical properties and wear resistance of cup liner via irradiation process requires investigation. This paper aims to understand the effect of UV (0.03 J/cm2) and gamma (25 kGy) irradiation on mechanical properties and scratch resistance of compression molded UHMWPE composites reinforced with alumina (Al2O3), hydroxyapatite (HAp) and carbon nanotubes (CNTs). After irradiation, nearly 100% increased crystallinity of polyethylene, due to recrystallization, helped in enhancing the hardness and elastic modulus by ~1.5 times compared to that of as-processed UHMWPE (Hardness: ~70 MPa and Elastic modulus: ~1.25 GPa). The recrystallization was not favored by the presence of nano-reinforcements in irradiated UHMWPE based nanocomposites, and caused deterioration in the mechanical properties. The micro-scratch results revealed the remarkable wear resistance (i.e., 1.5 to 2 times lower wear rate) of irradiated samples than that of as-processed samples. Mouse fibroblast L929 in vitro cell culture test confirmed the cytocompatibility of irradiated samples. This study indicated that the UV and gamma irradiated UHMWPE nanocomposites are the challenging candidates as acetabular cup liner.

Calcineurin, the conserved protein phosphatase and target of immunosuppressants, is a critical mediator of Ca2+ signaling. Here, to discover calcineurin-regulated processes we examined an understudied isoform, CNAβ1. We show that unlike canonical cytosolic calcineurin, CNAβ1 localizes to the plasma membrane and Golgi due to palmitoylation of its divergent C-terminal tail, which is reversed by the ABHD17A depalmitoylase. Palmitoylation targets CNAβ1 to a distinct set of membrane-associated interactors including the phosphatidylinositol 4-kinase (PI4KA) complex containing EFR3B, PI4KA, TTC7B and FAM126A. Hydrogen-deuterium exchange reveals multiple calcineurin-PI4KA complex contacts, including a calcineurin-binding peptide motif in the disordered tail of FAM126A, which we establish as a calcineurin substrate. Calcineurin inhibitors decrease PI4P production during Gq-coupled GPCR signaling, suggesting that calcineurin dephosphorylates and promotes PI4KA complex activity. In sum, this work discovers a calcineurin-regulated signaling pathway which highlights the PI4KA complex as a regulatory target and reveals that dynamic palmitoylation confers unique localization, substrate specificity and regulation to CNAβ1.

Vascular calcification associated with high plasma phosphate (Pi) level is a frequent complication of hyperglycemia, diabetes mellitus, and chronic kidney disease. BGP-15 is an emerging anti-diabetic drug candidate. This study was aimed to explore whether BGP-15 inhibits high Pi-induced calcification of human vascular smooth muscle cells (VSMCs) under normal glucose (NG) and high glucose (HG) conditions. Exposure of VSMCs to Pi resulted in accumulation of extracellular calcium, elevated cellular Pi uptake and intracellular pyruvate dehydrogenase kinase-4 (PDK-4) level, loss of smooth muscle cell markers (ACTA, TAGLN), and enhanced osteochondrogenic gene expression (KLF-5, Msx-2, Sp7, BMP-2). Increased Annexin A2 and decreased matrix Gla protein (MGP) content were found in extracellular vesicles (EVs). The HG condition markedly aggravated Pi-induced VSMC calcification. BGP-15 inhibited Pi uptake and PDK-4 expression that was accompanied by the decreased nuclear translocation of KLF-5, Msx-2, Sp7, retained VSMC markers (ACTA, TAGLN), and decreased BMP-2 in both NG and HG conditions. EVs exhibited increased MGP content and decreased Annexin A2. Importantly, BGP-15 prevented the deposition of calcium in the extracellular matrix. In conclusion, BGP-15 inhibits Pi-induced osteochondrogenic phenotypic switch and mineralization of VSMCs in vitro that make BGP-15 an ideal candidate to attenuate both diabetic and non-diabetic vascular calcification.

The gas-phase kinetics for the reactions of OH radicals and Cl atoms with 1,1,1,3,3,3-hexafluoro-2-methyl-2-propanol (HF2M2P) were measured at temperatures between 268 and 363 K using the relative rate experimental technique. Methane and acetonitrile were used as reference compounds to measure the rate coefficients of the title reactions. For the reactions of HF2M2P with OH radicals and Cl atoms, the rate coefficients were measured to be (7.07 ± 1.21) × 10-15 and (2.85 ± 0.54) × 10-14 cm3 molecule-1 s-1, respectively, at 298 K. The obtained Arrhenius expressions for the reactions of HF2M2P with OH radicals and Cl atoms are kHF2M2P + OHExp - (268 - 363 K) = (7.84 ± 0.75) × 10-14 exp [-(717 ± 59)/T] and kHF2M2P + ClExp - (268 - 363 K) = (3.21 ± 0.45) × 10-12 exp [-(1395 ± 83)/T] cm3 molecule-1 s-1. In addition to the experimental measurements, computational kinetic calculations were also performed for the title reactions at the M06-2X/MG3S//M06-2X/6-31 + G(d,p) level of theory using advanced methods such as the canonical variational transition-state theory coupled with small curvature tunneling corrections at temperatures between 200 and 400 K. Theoretical calculations reveal that the H-abstraction from the CH3 group is a more favorable reaction channel than that from the OH group. Thermochemistry, branching ratios, cumulative atmospheric lifetime, global warming potential, acidification potential, and photochemical ozone creation potential of HF2M2P were calculated in the present investigation.

The gas-phase kinetics of the reactions of IO radicals with ethyl formate (EF) and ethyl acetate (EA) were investigated experimentally using cavity ring-down spectroscopy (CRDS). IO radicals were generated in situ in the CRD reaction zone by photolyzing a mixture of (CH3I + O3 + N2) at 248 nm and thereby probed at 445.04 nm. The rate coefficients for the reactions (IO + EF) and (IO + EA) were measured at a total pressure of 65 Torr of N2 in the temperature range of 258–358 and 260–360 K, respectively. The rate coefficients for the reactions (IO + EF) and (IO + EA) were measured experimentally at room temperature to be kExpt,298KIO+EF = (3.38 ± 0.67) × 10−14 and kExpt,298KIO+EA = (1.56 ± 0.30) × 10−13 cm3 molecule−1 s−1, respectively. The effects of pressure and photolysis laser fluence on the kinetics of test reactions were found to be negligible within the experimental uncertainties for the studied range. To complement our experimental findings, the kinetics of the title reactions were investigated theoretically using canonical variational transition state theory (CVT) with small curvature tunnelling (SCT) at the CCSD(T)//M06-2X/def2-SV(P) level of theory in temperatures between 200 and 400 K. Very good agreement was observed between the experimentally measured and theoretically calculated rate coefficients for both the reactions at 298 K. The thermochemical parameters as well as the branching ratios for the title reactions are also discussed in this study.

The introduction of Bruton's tyrosine kinase inhibitor ibrutinib has made a significant progress in the treatment of chronic lymphocytic leukemia and other B-cell malignancies. Due to the reduction of cytokine release, it is effective in chronic graft-versus-host disease, and its use has also been suggested in autoimmune diseases and in prevention of COVID-19-associated lung damage. Despite this effect on the immune response, we report a severe hypersensitivity reaction in a 76-year-old male patient diagnosed with prolymphocytic leukemia. Four weeks after the ibrutinib start, non-oliguric acute kidney injury with proteinuria and microscopic hematuria developed and that was accompanied by lower limb purpuras and paresthesia. Renal biopsy revealed acute interstitial nephritis. Employing 1 mg/kg methylprednisolone administration, serum creatinine decreased from 365 μmol/L to 125 μmol/L at 11 days and the proteinuria-hematuria as well as the purpura, paresthesia resolved. Three months later at stabile eGFR of 56 ml/min/1.73 m2 methylprednisolone was withdrawn and a rituximab-venetoclax treatment was initiated without side effects. We conclude that despite the beneficial effect on cytokines response in Th1 direction, ibrutinib can cause acute interstitial nephritis. Early detection, discontinuation of ibrutinib, glucocorticoid administration may help to better preserve renal function, thereby lowering the risk of potential subsequent kidney injury.

Background: Antithrombotic/anticoagulation effects of direct oral anticoagulants (DOACs) are dose-dependent. However, recent observations suggest that administering lower dose DOACs may better protect against all-cause mortality. We investigated whether, in patients with established atherosclerosis, DOAC dose selection would affect the risk of all-cause mortality. Methods: We performed a structured literature research for controlled trials allowing random assignment to a lower dose DOAC, a higher dose DOAC, or control therapy in patients with established atherosclerosis. Pooled risk ratios (RRs) of all-cause mortality in lower and higher dose DOACs versus control therapy were estimated using a random-effect model. Results: Atherosclerosis manifested as acute coronary syndrome (n=17,220), stable coronary (CAD) and/or peripheral artery disease (PAD) (n=27,395) or CAD associated with atrial fibrillation (n=4,510). Antithrombotic doses of rivaroxaban (2.5 mg or 5.0 mg BID) or dabigatran (50 mg, 75 mg, 110 mg, or 150 mg, BID) were tested in three trials versus single or dual antiplatelet control therapy, whereas anticoagulation doses of edoxaban (30 mg or 60 OD) were tested versus warfarin in one trial. Compared to control, patients receiving lower dose (RR 0.80, 95% CI 0.73-0.89, pI²=0%), but not those receiving higher dose DOACs (RR 0.95, 95% CI 0.87-1.05, p=0.3074, I²=0%), had a significant reduction of all-cause mortality. Benefit from lower dose DOACs remained after sensitivity analysis or direct comparison with higher dose DOACs (RR 0.84, 95% CI 0.76-0.93, p=0.0009, I²=0%). Conclusions: Within antithrombotic/anticoagulation regimens of DOAC administration, selection of lower dose appears to protect from all-cause mortality in patients with established atherosclerosis.

Metal matrix composites proving their significance in enhanced mechanical properties gratifying the demands over non-alloy materials created an increased demand in the research evolvements. Revolution for are silient material in demand of less weight to density ratio can be propagated with hybrid nanocomposite multi-phase material realm. This in turn promises outstanding results based on factors considered. Since in Advancement of hybrid composites through retrospections the tailoring of a nano Metal matrix composition is an idealistic compulsion alter for futuristic extreme less weight density high strength materials. This paper mainly focuses in manufacturing of an Aluminium tailored Nano MMC’s (Al (8081)-Zr/Mg/TiO2) showing supreme enhancement in tribological performance with the nano composition of 9 wt% and 31 wt% mixture of Zr, Mg, TiO2 ratio are characterized, thereby attempting the proof of existence in building for extruding boarders in NMMC material applications having greater mechanical properties.

This contribution reports on the biosynthesis of Nanoscaled Zinc oxide nanoparticles (ZnO-NPs) using natural extracts from various parts of the Moringa Oleifera as effective chelating agents. More precisely, natural extracts from flowers, seeds and leaves of Moringa Oleifera as chelating and/or oxidizing/reducing agents of zinc nitrate hexahydrate are reported for the first time in the current literature. The structural and optical properties of ZnO-NPs obtained by the leaves are slightly different from those obtained with the other extracts. The average crystallite sizes of ZnO-NPs calculated via X-rays diffraction analysis are found to be 13.2, 13.9, and 10.8 nm for ZnO-NPs synthesized by the flowers, seeds, and leaves respectively while the direct band gap values deducted from Tauc approximation are 3.12, 3.18 and 3.25 eV. From the photoluminescence analysis at room temperature, a broad band in the visible centered around 450 nm is obtained for all the zinc oxide nanoparticles. One major bioactive compound for each solution extract was used to propose a mechanism of the reaction of ZnO-NPs formation: L-ascorbic acid for the leaves, quercetin for the flowers and oleic acid for the seeds.

Cadmium oxide (CdO) nanoparticles were synthesized for the first time via an eco-friendly, simple and cost effective green synthesis method mediated by corn husk extract. Indeed, the corn husk extract acted as an effective chelating agent in facilitating the formation of the CdO nanoparticles. XRD analysis confirmed the formation of highly crystalline face-centred cubic CdO nanoparticles. The structural morphology and the constituents of the resultant CdO nanoparticles were investigated by High Resolution – Scanning Electron Microscopy (HR-SEM) and Energy Dispersive X- rays Spectroscopy (EDS). Attenuated Total Reflection – Fourier Transformer Infrared spectroscopy (ATR-FTIR) and Raman spectroscopy measurements have been obtained to complete the structural investigation. UV – Visible spectroscopy analysis showed a wide absorbance spectral range of 250 – 2500 nm. Consequently, the CdO nanoparticle displayed photoluminescence emission peak at 508 nm.

The present work reports on the bio-synthesis and characterization of cadmium oxide nanoparticles (CdO) which were prepared via green synthesis method validating for the first time that oranges peel skin (Citrus x Sinensis) extract is an effective bio-oxidizing/bio-reducing /chelating agent. The prepared nanoparticles were characterized by various techniques such as X-rays diffraction, attenuated total reflection-Fourier transform infrared, Photoluminescence as well as diffuse reflectance. Synthesized samples annealed at various temperature of 200 °C, 300 °C, 400 °C reveal Bragg peaks which were matched to fcc structure of Monteponite CdO while ATR analysis show absorption bands at 548 and 617 cm−1 characteristic of CdO. Photoluminescence spectroscopy analysis shows emission peaks centered at 520 nm meanwhile diffuse reflectance measurement recorded reflectance of 60%, 15%, 8% for samples annealed at 400 °C, 300 °C, 200 °C with respective bandgap of 2.19 eV, 2.42 eV, 2.45 eV.

Kinetics for the reactions of methyl-2-methyl butanoate (M2MB) and methyl-3-methyl butanoate (M3MB) with OH radicals were carried out using the relative rate technique with gas chromatography-flame ionization detection (RR-GC-FID) in the temperature range of 268-363 K and at 760 Torr of N2. The temperature-dependent rate coefficients (k in cm3 molecule-1 s-1) for the reaction of M2MB with OH radicals from 268 to 363 K were measured to be k268 KM2MB + OH = (4.62 ± 1.50) × 10-12, k283 KM2MB + OH = (4.46 ± 1.41) × 10-12, k298 KM2MB + OH = (4.27 ± 1.20) × 10-12, k313 KM2MB + OH = (3.99 ± 1.06) × 10-12, k343 KM2MB + OH = (3.65 ± 0.94) × 10-12, and k363 KM2MB + OH = (3.53 ± 0.80) × 10-12, respectively. Similarly, the temperature-dependent kinetics for the reaction of M3MB with OH radicals were measured to be k268 KM3MB + OH = (4.49 ± 1.46) × 10-12, k283 KM3MB + OH = (4.40 ± 1.36) × 10-12 , k298 KM3MB + OH = (4.14 ± 1.18) × 10-12 , k313 KM3MB + OH = (3.90 ± 1.06) × 10-12 , k343 KM3MB + OH = (3.52 ± 0.85) × 10-12, and k363 KM3MB + OH = (3.42 ± 0.81) × 10-12 respectively. Furthermore, computational calculations were carried out for the title reactions using the CVT/SCT/ISPE method. In addition to this, the product analyses for the studied reactions were elucidated using gas chromatography-mass spectrometry (GC-MS) and gas chromatography-infrared spectroscopy (GC-IR) as analytical tools. Based on the identified products, the possible degradation mechanisms were proposed. Atmospheric lifetimes, radiative forcings (RFs), global warming potentials (GWPs), and photochemical ozone creation potentials (POCPs) were also estimated.

Ti6Al4V alloy composite coatings in-situ reinforced with TiB-TiN were deposited on Ti substrate using plasma spraying. Influence of plasma power (50 and 60 kW) and deposition speed (40 and 50 mm/s) on coating microstructure and bio-tribocorrosion performance was analyzed. Process parameters found to have strong influence on the tribocorrosion behavior and the material loss/damage of these coatings was found to be significantly less than that of Ti substrate. However, corrosion played a dominant role in affecting the wear and overall damage of all materials. Present in-situ composite coatings reinforced TiB-TiN exhibited superior tribocorrosion resistance than Ti substrate as a result of their high hardness and non-passivating nature.

Growing NH4+ content of groundwater results in increasing exchangeable and fixed ammonium ion content of the soil. NH4+ bond in the soil may go again into solution parallel with the dilution of the soil solution but at a slower rate than fixing. This process influences significantly the NH4+ content of the soil. In settlements with no sewerage system the high NH4+ content of sewage flowing out of uninsulated septic tanks may increase the fixed NH4-N content of the soil that could have a significant effect on the quality of groundwater even after the potential disappearance of pollution sources.In this study the effects of the fixed NH4-N content of the soil around an uninsulated residential septic tank on the purification processes of the groundwater were investigated. The septic tank in the study area was dismantled in 2014 after 27 years of operation as a sewerage system was constructed. When the tank was still in operation in 2012 and 2013, very high, 55–75 mg l-1 NH4+ content was measured in the water of the monitoring well 1 metre from the tank in the course of seasonal sampling. When sewage outflow was terminated in 2014 concentrations decreased right away but even 5 years after pollutant supply was stopped, concentrations (35–57 mg l-1) highly exceeding the pollution limit (0.5 mg l-1) were measured. Considering this very high concentration, it can be assumed that great amount of NH4+ is still released into the groundwater.In order to prove this, the exchangeable and fixed NH4-N and NO3-N contents of the soil were determined by 20 cm down to a depth of 4 metres (2019). The measurements indicated the significant accumulation of exchangeable and fixed NH4-N in the zone between 220 and 400 cm. Highest fixed NH4-N concentrations of 457 mg l-1 were found between 220 and 240 cm suggesting that sewage outflow was most intense at this depth. Slow decrease in concentrations can be observed in deeper zones but concentrations higher than 350 mg l-1 were measured between 220 and 380 cm. Based on correlation analyses, the quantity of fixed NH4-N shows no correlation with the soil texture thus it can be stated that the vertical pattern of NH4-N content is determined dominantly by sewage outflow and its depth. In the unsaturated zone of the borehole a significant accumulation of NO3-N was also identified. The maximum of NO3-N was found in the zone between 100 and 140 cm. The peak nitrate calculated for NO3- ion with a value >1300 mg kg-1 is 2.5 times the limit set for the nitrate content of the geological medium.Based on the results, exchangeable and fixed NH4-N contents in the soil are still very high, 5 years after sewage outflow was stopped. The continuous solution of this component still contributes to the high NH4+ content of the groundwater. As a result, the contaminated soil in the immediate environment of the septic tank is still a pollution source.

In this work, biomass-based platform molecule lactic acid conversion to acrylic acid has been studied. A series of lanthanum phosphate (LaP) catalysts prepared by varying the lanthanum to phosphorus (La/P) mole ratio (i.e., 0.2, 0.35, 0.5, 1.0, and 2.0) and also prepared at different calcination temperatures (i.e., 400, 500, 600, and 800 °C) were investigated. The catalysts were characterized by using different techniques and tested in the dehydration of lactic acid (LA) to acrylic acid (AA) production. All the synthesized catalysts were characterized to analyze the physicochemical properties such as degree of crystallinity, total surface acidity, specific surface area, and morphology. The La/P mole ratio was found to be significant in designing the optimized catalytic system. The NH3-TPD results imply that all the catalysts exhibited varied amount of total acidity with phosphate loadings, which are mostly weak acid sites. The weak acid sites which are mainly Lewis acidity type played an important role in producing AA selectively and efficiently from the LA conversion. The most optimized reaction conditions were determined to obtain the highest LA conversion, selectivity, and AA yield. The catalyst with an La/P mole ratio of 0.35 and calcined at 500 °C exhibited the best performance with complete LA conversion, AA selectivity of ~ 74%, and a maximum yield of AA of ~ 74%. Furthermore, the LaP(0.35)[500] catalyst was successfully tested at three different time on streams and found to be stable.

Herein, we report laser powder bed fusion (L-PBF) of dry-mixed Ti6Al4V + Si3N4 powder to create in-situ titanium matrix composites. The dry-mixed Ti6Al4V powder with 5 wt.% Si3N4 was processed using l -PBF at varying laser energy densities, between 44 and 133 J/mm3, by changing the laser scan speed (400–1200 mm/s) at constant laser power of 96 W, layer thickness of 20 μm and scan spacing of 90 μm. The selected samples were examined for microstructural evolution, in-situ reaction products and hardness. The results showed that the in-situ reaction between liquid titanium and Si3N4 forms fine TiN and Ti5Si3 reinforcements in these l -PBF processed samples. However, the irregular shape and fine size of Si3N4 reduced the feedstock flowability, and the composites could not be processed with laser energy density (E) l -PBF but further improvement is required through adjusting Si3N4 powder attributes (size, shape) and concentration.

Toll-like receptor (TLR) recruitment to phagosomes in dendritic cells (DCs) and downstream TLR signaling are essential to initiate antimicrobial immune responses. However, the mechanisms underlying TLR localization to phagosomes are poorly characterized. We show herein that phosphatidylinositol-4-kinase IIα (PI4KIIα) plays a key role in initiating phagosomal TLR4 responses in murine DCs by generating a phosphatidylinositol-4-phosphate (PtdIns4P) platform conducive to the binding of the TLR sorting adaptor Toll-IL1 receptor (TIR) domain-containing adaptor protein (TIRAP). PI4KIIα is recruited to maturing lipopolysaccharide (LPS)-containing phagosomes in an adaptor protein-3 (AP-3)-dependent manner, and both PI4KIIα and PtdIns4P are detected on phagosomal membrane tubules. Knockdown of PI4KIIα-but not the related PI4KIIβ-impairs TIRAP and TLR4 localization to phagosomes, reduces proinflammatory cytokine secretion, abolishes phagosomal tubule formation, and impairs major histocompatibility complex II (MHC-II) presentation. Phagosomal TLR responses in PI4KIIα-deficient DCs are restored by reexpression of wild-type PI4KIIα, but not of variants lacking kinase activity or AP-3 binding. Our data indicate that PI4KIIα is an essential regulator of phagosomal TLR signaling in DCs by ensuring optimal TIRAP recruitment to phagosomes.

The influence of exposing carcinoma cells to a static magnetic field (SMF) and low-intensity pulsed ultrasound (LIPUS), for different durations (15–45 min/d), in the presence of magnetic and non-magnetic drug carriers, on their in vitro inhibition is examined. Increasing the exposure time by 15 min/d decreased the culture duration by 24 h to achieve the same level of inhibition in colon (HCT116) and hepatocellular (HepG2) cells. Cell cycle analysis revealed enhanced cellular blockage in G1 and S phases with SMF + LIPUS exposure, and exposure for 45 min/d completely suppressed the S → G2 transition. Apoptosis of both types of cells increased with SMF + LIPUS treatment time, and HepG2 cells exhibited elevated necrosis with >30 min/d exposure. HepG2 cells also had higher amounts of reactive oxygen species (seven- to eightfold) than HCT116 cells (two- to sixfold), suggesting treatment effectiveness is cell and drug carrier dependent. The accelerated cellular activities are attributed to the enhanced internalization of drug carriers as a consequence of destabilized cellular membranes caused by the SMF + LIPUS-generated mechanical and electrical stimuli.