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A study has been performed using a crystal plasticity based finite element method to understand the effect of various stress states and crystal orientations with respect to loading direction for FCC single crystals in both hydrogenated and nonhydrogenated environment. Simulations have been performed for a variety of stress triaxilaities, Lode parameters, crystal orientations and hydrogen concentrations. It has been observed that crystal orientation has a varied effect on the influence of hydrogen on plastic deformation and void growth. Hydrogen in trap distribution at various stages of the deformation process was also found to be influenced by crystal orientation. From analyses performed, an analytical relationship between normalised void fraction and equivalent strain has been derived.

The synthesis of amoxicillin derivatives was carried out by reaction of amoxicillin with p-aminophenol which was catalyzed by MgF2. The aims of this research was to characterize amoxicillin derivatives. The compounds have been characterized by physical and chemical tests including organoleptic test, melting point test, pH test, Rf value test and maximum wavelength test. The results showed that the compounds having physical characteristics including organoleptic was brown powder and bitter taste with 238°C melting point. The chemical characteristic showed that Rf value was about 0.6, a pH was 6,1 and a maximum wavelength was 311 nm.

We recently reported that adoptive transfer of cytolytic Natural Killer cells (cNKs) from the Reduced Uterine Perfusion Pressure (RUPP) rat induces a preeclampsia (PE)-like phenotype in pregnant rats, accompanied by increased TNF-α. The purpose of this study was to investigate a role for increased TNF-α to induce oxidative stress (ROS), decrease nitric oxide (NO) bioavailability, and induce vascular dysfunction as mechanisms of hypertension (HTN) and intrauterine growth restriction (IUGR) in RUPPs. Pregnant Sprague Dawley rats underwent the RUPP or a Sham procedure on gestation day (GD) 14. On GDs 15 and 18, a subset of Sham and RUPP rats received i.p.injections of vehicle or 0.4 mg/kg of Etanercept (ETA), a soluble TNF-α receptor (n = 10/group). On GD18, Uterine Artery Resistance Index (UARI) was measured, and on GD19, mean arterial pressure (MAP), fetal and placental weights were measured, and blood and tissues were processed for analysis. TNF-α blockade normalized the elevated MAP observed RUPP. Additionally, both fetal and placental weights were decreased in RUPP compared to Sham, and were normalized in RUPP + ETA. Placental ROS was also increased in RUPP rats compared to Sham, and remained elevated in RUPP + ETA. Compared to Sham, UARI was elevated in RUPPs while plasma total nitrate was reduced, and these were normalized in ETA treated RUPPs. In conclusion, TNF-α blockade in RUPPs reduced MAP and UARI, improved fetal growth, and increased NO bioavailability. These data suggest that TNF-α regulation of NO bioavailability is a potential mechanism that contributes to PE pathophysiology and may represent a therapeutic target to improve maternal outcomes and fetal growth.

This paper presents a study of the combined effect of PVA (powder form) and fly ash on the mechanical properties of concrete. Three different parameters (PVA, fly ash, and different patterns of curing) were used. The Taguchi statistical method has been used to decrease the number of concrete specimens from 160 to 54. Different percentages of PVA (1% and 2%) with fly ash (10% and 20%) were used in 36 concrete samples. Afterward, all samples were cured in three different ways namely: Open air-dry curing, normal water curing, and temperature bath curing. Samples with 1% PVA and 10% Fly ash shows the highest compressive strength, tensile strength, and modulus of elasticity. The improvement in strength is due to the interaction of PVA and FA with cement, filling pores, and strengthening the bond between the cement. Furthermore, the samples kept in water curing exhibited the greatest strength among all types of curing.

Phaseolus vulgaris Linn commonly known as red kidney bean, it is enriched in protein, carbohydrates and dietary fibres. Beans have nutritional and health benefits and also possess antimicrobial, antihyperglycemic, antioxidant and anticancer activity due to presence of bio-active chemical constituents. The following study was carried out to evaluate the anti-depressant activity of Phaseolus vulgaris fixed oil (PVFO) using forced swim test and tail suspension test in mice. In this study animals assigned into four groups (n=7). Group I: Control normal saline (2 mL/Kg), Group II: PVFO I (2 mL/Kg), Group III: PVFO II (4 mL/Kg) and Group IV: standard amitriptyline (10 mg/Kg). The results were significant and indicated the possible anti-depressant role of Phaseolus vulgaris fixed oil.

Oral biofilms harbour gram-negative bacterial antigen lipopolysaccharide (LPS) involved in oral cancer progression and gram-positive bacterial surface-associated adhesive, lipoteichoic acid (LTA). Thus, we hypothesised that LPS and LTA together would increase the proliferation of cancer cells compared to stimulation by LPS alone. Oral cancer cell lines SCC4, SCC9, SCC25, Cal 27 and the normal oral cell line, OKF6, were studied. The bacterial antigen stimulation indices were determined using the MT Glo assay. Cell proliferation after bacterial antigen stimulation was validated by clonogenic assays. Phosphokinase array, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blot were employed to study proliferative and apoptotic pathways in bacterial antigen-stimulated cells. Bacterial antigens significantly stimulated Cal 27 (p ≤ 0.001) alone. SCC4 and SCC9 showed negligible stimulation with either antigen, while SCC25 results were comparable to OKF6. The combined antigen stimulation of Cal 27 led to a decrease in phosphorylated p53 and β-catenin and higher PI3K compared to LPS only stimulated cells (p ≤ 0.001). Combined bacterial antigen stimulation results in increased proliferation of Cal 27 cells due to lowering of tumor suppressor proteins and increased tumor proliferation-related proteins.

Interaction of sulphone based reactive dyes, designated as dye-1 and dye-2, with cationic micellar system of cetyltrimethylammonium bromide (CTAB), has been investigated by spectroscopic and conductometeric measurements. Efficiency of the selected micellar systems is assessed by the values of binding constant (K b ), partition coefficient (K x ) and respective Gibbs energies. Critical micelle concentration (CMC) of surfactant, electrostatic and hydrophobic interactions as well as polarity of the medium plays significant role in this phenomenon. The negative values of Gibbs energies of binding (∆G b ) and partition (∆G p ) predicts the feasibility and spontaneity of respective processes. Similarly negative values of ∆G m and ∆H m and positive values of ∆S m , calculated from conductometeric data, further, revealed the exothermicity, spontaneity and, thus, stability of system. The results, herein, have disclosed the strong interaction between dye and surfactant molecules. The dye-2 has been observed to be solubilized to greater extent, as compared to dye 1, due to strong interaction ith hydrophiles of CTAB and accommodation of its molecules in palisade layer of micelle closer to the micelle/water interface.

Herein, we synthesized poly(methacrylic acid) [p(MAAc] hydrogels by an effective and simple free radical polymerization process and then silver, cobalt, and their bimetallic nanoparticles (NPs) wer...

Lyophilic microgels based on Gum Acacia (GAC) were synthesized at room temperature and normal pressure. Briefly, high yield of the spherical shaped microgels of size ≤ 50 µm was obtained via introducing linear GAC and divinyl sulfone (DS) in the reverse micelle cores of NBSS in the stirring gasoline. The GAC microgels were then utilized as synthetic micro-templates for fabricating their nanocomposites with Cobalt (Co), to subsequently produce GAC-Co nanocomposite microgels. The as synthesis GAC based microgels and the GAC-Co microgels were characterized through FTIR, TGA, DSC, SEM, EDS, and TEM. Different amounts of GAC-Co microgels were used as nano-catalyst for the degradation of poisonous aromatic compounds and an Azo dye in aqueous medium. Briefly, 1 g GAC-Co microgels degraded 100 mL (250 ppm solution) of each the aforementioned compounds in ≤ 25 min at neutral pH. The increase in the kinetic parameter i.e., rate constant (kapp) value with increase in the GAC-Co nanocomposite microgels amounts manifests the positive impact of the fabricated nano-catalyst on these compounds degradation at room temperature.

In this work, nine new mixed-ligand complexes with the general formula [CuBr(TPP)2Tu1–9] were synthesized. The copper(I) complexes of triphenylphosphine (TPP) and different N,N′-disubstituted thioureas (Tu) were characterized via spectroscopic techniques including Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (1H, 13C, and 31P NMR), and single-crystal X-ray diffraction (SC-XRD). The complexes were synthesized via the direct reaction of bromo(tris(triphenylphosphine)copper(I)) [BrCu(PPh3)3] precursor and thiourea ligand solution under ambient conditions. Complexes 1, 2 and 3 crystallized in a triclinic system with the P space group. Each complex is mononuclear, and the copper atom is tetrahedrally attached to two TPP groups through the phosphorous atom, one thiourea molecule through the sulfur atom and one bromine atom. The synthesized compounds were docked with a DNA macromolecule to predict their binding site and it was found that all molecules showed favorable binding to the DNA minor grooves. The DNA interaction studies of the representative complexes demonstrated their efficient DNA binding affinities. Based on the docking and DNA interaction results, complex 7 was found to be the best binder with a docking affinity of 382.2 kJ mol−1 and binding constant of 3.96 × 104 M−1. This compound tends to interact with the minor groove through the bromine atom positioning the side triphenylphosphine rings along the X-axis of the groove while keeping the 1-(2-chlorobenzyl)-3-(3-(trifluoromethyl)phenyl)thiourea ring on the outside.

Graphene oxide templated cobalt (GO–Co) and graphene oxide templated silver (GO–Ag) nanocomposites were synthesized and used as catalysts in the reduction of 4-Nitrophenol (4-NP), 2-Nitrophenol (2-NP) and 2-Nitroaniline (2-NA). Almost evenly distributed nanoparticles of Ag and Co were obtained on GO sheets and the diameters of most of the particles were in the range of 5–15 nm. The maximum apparent reduction rate (kapp) for 4-NP was found to be 0.58 min−1 and 0.67min−1 with corresponding activation energies of 28.79 and 16.54 kJ mol−1 in the presence of GO–Ag and GO–Co catalysts, respectively. The kapp for GO–Co cataly-zed reduction of 2-NP and 2-NA were found as 0.10 and 0.06 min−1, respectively. Catalytic activity of GO–Ag was decreased by 25% in the fifth cycle while that of GO–Co was decreased to 47% in the fourth cycle for the reduction of 4-NP. Overall, GO–Ag showed superior catalytic behaviour as compared to GO–Co.

The aim of this experiment was to determine the best PGPR concentration to support coffee shoot grafting. The experiment was carried out in the form of a completely randomized design (CRD) consisting of 4 treatments, namely without PGPR or control K0 (concentration 0 ml L-1 water), K1: 10 ml, L-1 water, K2: 20 ml L-1 water, and K3: 30 ml. L-1 water is given to each polybag. Each treatment had 4 replications so that there were 16 experimental units. The results showed that giving PGPR with a concentration of 30 ml L-1 of water to shoot grafts gave the best results on shoot height and shoot diameter growth. Whereas at a concentration of 10 ml.L-1 water gave the best effect on the increase in the number of leaves of coffee shoot grafting seeds.

A crystal plasticity-based finite element study is performed to understand hydrogen effects on void growth in single crystals of austenitic stainless steel. The model assumes plastic deformation is driven primarily by dislocation motion and captures the influence of hydrogen. Hydrogen effects are incorporated by assuming agreement with the hydrogen enhanced localised plasticity (HELP) mechanism. Despite experimental evidence, hydrogen effect on face centred cubic (FCC) crystals has hitherto not been considered in a numerical void growth model for a wide range of stress states. For the first time, the influence of hydrogen on void growth for different Lode parameters at single crystalline levels is investigated for a range of stress triaxialities in FCC crystals. Hydrogen was found to increase equivalent stresses and hardening responses for various stress triaxialities and Lode parameters. Hydrogen also induces higher void growth response at different stress states, and this was more pronounced at high stress triaxialities.

Hydrogels of Acacia gum (AG) were synthesized in the reverse micelle core of sodium bis (2-ethylhexyl) sulfosuccinate (AOT) in gasoline medium. The as synthesized hydrogels were used as template to prepare Silver nanoparticle (AgNPs) in situ via the reduction mechanism of NaBH4. The successful synthesis of bare hydrogels and AgNPs loaded nanocomposite hydrogels (AG–Ag hydrogels) were characterized through Fourier Transform Infrared spectroscopy, Thermal gravimetric analysis, Differential Scanning Calorimetry, Scanning Electron Microscopy, energy dispersive X-ray spectroscopy and Transmission Electron Microscopy, and Atomic Absorption Spectroscopy (AAS). Different feeds of the as fabricated GA-Ag hydrogels were used to catalyze the well-known reactions of 4-nitrophenol (4-NP), 2-nitrophenol (2-NP), and Methyl Orange (MO) reduction in aqueous medium at ambient physical conditions. Remarkably, 1000 mg/L of AG–Ag hydrogels with reduced 4-NP and 2-NP into its counterparts, 4-aminophenol and 2-aminophenol in 24 min and 15 min, respectively at room temperature. Similarly, 1000 mg/L of AG–Ag hydrogels reduced MO completely within 25 min. The aforementioned catalytic reactions followed pseudo first order rate kinetics, and it was found that the value of rate constant (kapp) increased by increasing the catalyst amount which, thereby confirms the high conversion rate of the reactants. Schematic illustration of fabrication and catalytic action of AgNPs grown inside the pre-synthesized AG Hydrogel matrices.

The in-situ stabilization of Ag nanoparticles is carried out by the use of reducing agent and synthesized three different types of hydrogen (anionic, cationic, and neutral) template. The morphology, constitution and thermal stability of the synthesized pure and Ag-entrapped hybrid hydrogels were efficiently confirmed using scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and thermo gravimetric analysis (TGA). The prepared hybrid hydrogels were used in the decolorization of methylene blue (MB) and azo dyes congo red (CR), methyl Orange (MO), and reduction of 4-nitrophenol (4-NP) and nitrobenzene (NB) by an electron donor NaBH4. The kinetics of the reduction reaction was also assessed to determine the activation parameters. The hybrid hydrogen catalysts were recovered by filtration and used continuously up to six times with 98% conversion of pollutants without substantial loss in catalytic activity. It was observed that these types of hydrogel systems can be used for the conversion of pollutants from waste water into useful products.

Purpose Determining the role of DYNC2H1 variants in nonsyndromic inherited retinal disease (IRD). Methods Genome and exome sequencing were performed for five unrelated cases of IRD with no identified variant. In vitro assays were developed to validate the variants identified (fibroblast assay, induced pluripotent stem cell [iPSC] derived retinal organoids, and a dynein motility assay). Results Four novel DYNC2H1 variants (V1, g.103327020_103327021dup; V2, g.103055779A>T; V3, g.103112272C>G; V4, g.103070104A>C) and one previously reported variant (V5, g.103339363T>G) were identified. In proband 1 (V1/V2), V1 was predicted to introduce a premature termination codon (PTC), whereas V2 disrupted the exon 41 splice donor site causing incomplete skipping of exon 41. V1 and V2 impaired dynein-2 motility in vitro and perturbed IFT88 distribution within cilia. V3, homozygous in probands 2–4, is predicted to cause a PTC in a retina-predominant transcript. Analysis of retinal organoids showed that this new transcript expression increased with organoid differentiation. V4, a novel missense variant, was in trans with V5, previously associated with Jeune asphyxiating thoracic dystrophy (JATD). Conclusion The DYNC2H1 variants discussed herein were either hypomorphic or affecting a retina-predominant transcript and caused nonsyndromic IRD. Dynein variants, specifically DYNC2H1 variants are reported as a cause of non syndromic IRD.

The process of self-assembly of riboflavin molecules in aqueous and binary mixtures of solvents was investigated by the spectroscopic method. It was shown that during the assembly of vitamin B2 molecules, dipole-dipole interaction occurs, as a result of which resonant splitting of excited electronic levels of riboflavin molecules occurs. And the observable hypo chromic effect is due to a decrease in the intense absorption capacity of the aggregated riboflavin molecules themselves.

Functionalization of multiwalled carbon nanotubes (MWCNTs) with amine group using 4,4′-diaminodiphenyl sulfone (DDS) is achieved after carboxylation of pure MWCNTs (p-MWCNTs). p-MWCNTs, a-MWCNTs (a...

Here in, we demonstrate facile fabrication of silver and palladium nanoparticles in dual responsive poly(N-isopropylacrylamide- co-2-Acrylamido-2-methylpropane sulfonic acid) microgel with temperature- and pH-dependent catalytic potential. Palladium-based catalyst showed better catalytic efficiency as compared to silver-based catalyst for degradation of Rhodamine-B and P-Nitrophenol in aqueous medium under the same set of reaction conditions. The responsive nature of the microgel was found to be useful to tune the catalytic activity of the as-prepared catalysts, and reduction rate was enhanced with the pH and temperature elevation of the reaction medium; however, the increasing trend was slowed in the volume phase transition region of the microgel. Under a specific set of reaction conditions, the reduction of Rhodamine-B was as fast as 0.968 and 0.571 min−1 when catalyzed with palladium and silver based catalysts, respectively. The hydrodynamic radius of the particles of microgel support was found to be in the range of 65-180 nm when pH and temperature of the medium were varied in the range of 2-12 and 25-45, respectively. The estimated diameter of silver and palladium nanoparticles fabricated in the microgel support under the same set of reaction conditions was 9-15 and 7-11 nm, respectively.

Rap1 is a small GTPase that has been implicated in dendritic development and plasticity. In this study, we investigated the role of Rap1 in axonal growth and its activation in response to neurotrophins and myelin-associated inhibitors. We report that Rap1 is activated by brain-derived neurotrophic factor and that this activation can be blocked by myelin-associated glycoprotein (MAG) or central nervous system myelin, which also induced increases in Rap1GAP1 levels. In addition, we demonstrate that adenoviral overexpression of Rap1 enhances neurite outgrowth in the presence of MAG and myelin, while inhibition of Rap1 activity through overexpression of Rap1GAP1 blocks neurite outgrowth. These findings suggest that Rap1GAP1 negatively regulates neurite outgrowth, making it a potential therapeutic target to promote axonal regeneration.

This is an up-to-date review on civil engineering application of polymeric composites filled with cement and fillers. Various combinations of polymer, glass fiber, and carbonaceous fillers have bee...

Background: Epiretinal membranes are avascular, fibrocellular membranes which develop on the inner most layer of the retina. These membranes can be idiopathic or secondary to the silicone oil injection after pars plana vitrectomy in patients with rhegmatogenous retinal detachment. When symptomatic, such membranes can cause decreased vision, visual distortion and sometimes diplopia. The purpose of this study was to compare the idiopathic epiretinal membranes versus silicone oil filled eyes epiretinal membranes in terms of their diagnostic and surgical features. Material and methods: The study was conducted at the Department of Ophthalmology, Services Hospital Lahore where 13 eyes with idiopathic epiretinal membranes (ERMs) and 13 eyes with silicone oil filled eyes epiretinal membranes (SOERMs) were evaluated from August 2017 to April 2019. The main diagnostic outcome was the preoperative Optical Coherence Tomographic (OCT) findings and main surgical outcome was peroperative time required for removal of epiretinal membranes. Results: Mean central retinal thickness of patients with SOERMs on OCT was 530.30µm, which was recorded one day before surgery. It was greater as compared to the central retinal thickness in patients with idiopathic ERMs which was 391.92 µm. The mean time required for the removal of SOERMs was 466.38 seconds. It was longer as compared to the time required to remove idiopathic ERMs which was 385.69 seconds. Conclusion: The SOERMs are relatively difficult to remove due to increased thickness and more adherent nature as compared to idiopathic ERMs which were single layer and relatively easy to remove.

Cyclic poly(2-ethyl-2-oxazoline) (PEtOx) with a degradable disulfide bond has been synthesized by combining cationic ring opening polymerization (ROP) and reversible thiol/disulfide exchange chemistry. In greater detail, a living linear PEtOx with two cationic propagating terminals was initially synthesized using 1,3-bis(bromomethyl)benzene as a difunctional initiator. Both the living ends of PEtOx were then reacted with potassium ethyl xanthate to afford α,ω-xanthate end-functionalized PEtOx (xanthate-PEtOx-xanthate). The xanthate groups were then in situ cleaved using n-butylamine as a cleaving agent as well as a base in the same reaction media, which produced α,ω-thiol end-functionalized PEtOx (HS-PEtOx-SH). The cyclic polymer was eventually obtained by the successive intramolecular oxidation coupling of the thiol terminals of HS-PEtOx-SH to form a disulfide bond as a ring-closure link. For the polymeric information, 1H NMR spectroscopy, SEC spectroscopy, MALDI-TOF-MS, and UV-visible spectroscopy were combined to characterize the linear and cyclic polymers. Ellman's assay was used to determine the thiol content in the cyclic and thiol terminated polymers. Clean cyclic PEtOxs with number-average molar masses around 2000 (2 K) and 4000 (4 K) g mol−1 were obtained at an unreported high polymer concentration of 5 g L−1 (ca. 2.5 × 10−3 M for the 2 K polymer and ca. 1.25 × 10−3 M for the 4 K polymer) in THF. In addition, the synthetic route was compared with the intramolecular copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction and proven to be more advantageous in terms of reactant concentration, yield, purification, and bonding reversibility.

In present study, the anti-inflammatory potential of a series of 2-(4-chlorobenzyl)-5-(di(5-substituted- 1H-indol-3-yl)methyl)-6-(4-substituted phenyl)imidazo[2,1-b][1,3,4]thiadiazoles (5a-e) were evuluated after characterizing through 1H NMR, 13C NMR spectral studies. Initial toxicity and anti-inflammatory efficacy of synthesized compounds is evaluated against RAW264.7 macrophages cell line to derive at their IC50 values. Compounds 5a-e are further tested for their anti-inflammatory activity in Swiss albino rats using the 1% carrageenan-induced paw edema model. Compound 5a is taken as the lead compound and is further considered for behavioural evaluations such as stair climbing and motility exercises. Paw edema is analyzed at time intervals of 0, 1, 2, 3, 4 and 24 h and stair climbing and motility tests are surveyed after 24 h of exposure to the test compound. The results of present study show that the compound 5a significantly reduces the paw thickness by 68% at p < 0.001 and increased the stair climbing (1.5 folds) and motility (1.6 folds) when compared to the 1% carrageenan rat group. Conclusively the results of present study show that compound 5a exhibits strong anti-inflammatory potential that can be used as a preclinical template for further investigations as an alternative therapy to the current NSAIDs.

A simple, efficient and eco-friendly method for the synthesis of 1,2-dihydroquinazolines has been developed using three-component reaction of readily available aromatic aldehydes, 2-aminobenzophenones, ammonium acetate with sulfamic acid as a green and recyclable catalyst. The significant features of this method include short reaction time, operational simplicity, high yields and high selectivity. Interestingly, the catalyst can be recovered and reused for up to four cycles without any loss in catalytic activity. By employing this method, a series of 23 compounds was synthesized and tested for antimicrobial activity against both Gram-positive and Gram-negative bacterial strains as well as a fungal strain. Among these, compounds 4l, 4v and 4w showed appreciable antibacterial activity selectively against Gram-positive bacteria, wherein compound 4w exhibited promising antibacterial activity with MIC value of 0.010 μMol L−1 against Staphylococcus aureus MTCC 96 and Micrococcus luteus MTCC 2470. In addition, 4w also showed promising bactericidal and biofilm formation inhibitory effects. Keywords: 1,2-Dihydroquinazolines, Sulfamic acid, Recyclability, Antimicrobial, Anti-biofilm

The drug delivery system (DDS) often causes toxicity, triggering undesired cellular injuries. Thus, developing supramolecules used as DDS with tunable self-assembly and nontoxic behavior is highly desired. To address this, we aimed to develop a tunable amphiphilic ABA-type triblock copolymer that is nontoxic to human blood cells but also capable of self-assembling, binding and releasing the clinically used drug dexamethasone. We synthesized an ABA-type amphiphilic triblock copolymer (P2L) by incorporating tetra(aniline) TANI as a hydrophobic and redox active segment along with monomethoxy end-capped polyethylene glycol (mPEG2k; Mw = 2000 g mol−1) as biocompatible, flexible and hydrophilic part. Cell cytotoxicity was measured in whole human blood in vitro and lung cancer cells. Polymer-drug interactions were investigated by UV–Vis spectroscopy and computational analysis. Our synthesized copolymer P2L exhibited tuned self-assembly behavior with and without external stimuli and showed no toxicity in human blood samples. Computational analysis showed that P2L can encapsulate the clinically used drug dexamethasone and that drug uptake or release can also be triggered under oxidation or low pH conditions. In conclusion, copolymer P2L is nontoxic to human blood cells with the potential to carry and release anticancer/anti-inflammatory drug dexamethasone. These findings may open up further investigations into implantable drug delivery systems/devices with precise drug administration and controlled release at specific locations.

Axonal regeneration in the mature CNS is limited by extracellular inhibitory factors. Triple knockout mice lacking the major myelin-associated inhibitors do not display spontaneous regeneration after injury, indicating the presence of other inhibitors. Searching for such inhibitors, we have detected elevated levels of histone H3 in human CSF 24 h after spinal cord injury. Following dorsal column lesions in mice and optic nerve crushes in rats, elevated levels of extracellular histone H3 were detected at the injury site. Similar to myelin-associated inhibitors, these extracellular histones induced growth cone collapse and inhibited neurite outgrowth. Histones mediate inhibition through the transcription factor Y-box-binding protein 1 and Toll-like receptor 2, and these effects are independent of the Nogo receptor. Histone-mediated inhibition can be reversed by the addition of activated protein C in vitro, and activated protein C treatment promotes axonal regeneration in the crushed optic nerve in vivo. These findings identify extracellular histones as a new class of nerve regeneration-inhibiting molecules within the injured CNS., Siddiq et al. report that elevated levels of histone H3 in human CSF 24 hours after spinal cord injury and that they are inhibitory to neurite outgrowth. Histone-mediated inhibition can be reversed by the addition of activated protein C in vitro and in vivo, mediated by phosphorylation of YB-1., Graphical Abstract Graphical Abstract