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Nanoporous silica membranes exhibit excellent H2/CO2 separation properties for sustainable H2 production and CO2 capture but are prepared via complicated thermal processes above 400 °C, which prevent their scalable production at a low cost. Here, we demonstrate the rapid fabrication (within 2 min) of ultrathin silica-like membranes (∼3 nm) via an oxygen plasma treatment of polydimethylsiloxane-based thin-film composite membranes at 20 °C. The resulting organosilica membranes unexpectedly exhibit H2 permeance of 280-930 GPU (1 GPU = 3.347 × 10-10 mol m-2 s-1 Pa-1) and H2/CO2 selectivity of 93-32 at 200 °C, far surpassing state-of-the-art membranes and Robeson's upper bound for H2/CO2 separation. When challenged with a 3 d simulated syngas test containing water vapor at 200 °C and a 340 d stability test, the membrane shows durable separation performance and excellent hydrothermal stability. The robust H2/CO2 separation properties coupled with excellent scalability demonstrate the great potential of these organosilica membranes for economic H2 production with minimal carbon emissions.

The presence of aggregates in monoclonal antibody (mAb) drug product (DP) formulations can present product quality challenges. Here we show that use of High Performance Size Exclusion Chromatography (HP-SEC), in conjunction with high-throughput dynamic light scattering (HT-DLS) analyses of mAb DPs can be a useful strategy to determine monomer content and the presence of aggregates under simulated stress conditions. This analytical approach was used to evaluate four commercially available mAb DPs under different conditions i.e.; original formulations, diluted, and thermo-mechanical stressed condition. Due to particle size limitations of HP-SEC columns, resulting in particles accumulating in the column frits prior to reaching the detector for analysis, there is a possibility that large mAb aggregates may not be detected. Both HP-SEC and HT-DLS were able to detect and resolve the mAb monomer (~10–12 nm) of the DPs in their recommended storage conditions. However, the ability to detect large aggregates (>40 nm) by both analytical methods differed, and HT-DLS was able to detect aggregates between 60 nm and 1400 nm under stress conditions. Our data indicates that HP-SEC, in conjunction with HT-DLS, may be beneficial to detect both mAb DP monomer content and multiple aggregate species (1–1000 nm) in the submicron size range.

Most examples of mixed-matrix membranes (MMMs) involve one type of polymer and one type of inorganic filler particle. Here, both polymer blending and MMM approaches are combined to form exceptional...

Ischemic stroke causes brain endothelial cell (BEC) death and damages tight junction integrity of the blood-brain barrier (BBB). We harnessed the innate mitochondrial load of endothelial cell-derived extracellular vesicles (EVs) and utilized mixtures of EV/exogenous heat shock protein 27 (HSP27) as a one-two punch strategy to increase BEC survival (via EV mitochondria) and preserve their tight junction integrity (via HSP27 effects). We demonstrated that the medium-to-large (m/lEV) but not small EVs (sEV) transferred their mitochondrial load, which subsequently colocalized with the mitochondrial network of the recipient primary human BECs. BECs treated with m/lEVs increased relative ATP levels and displayed superior mitochondrial function. Importantly, m/lEVs isolated from oligomycin (mitochondrial complex V inhibitor) or rotenone (mitochondrial complex I inhibitor)-exposed BECs (RTN-m/lEVs or OGM-m/lEVs) did not increase BECs ATP levels compared to naïve m/lEVs. In contrast, RTN-sEV and OGM-sEV functionality in increasing cellular ATP levels was minimally impacted in comparison to naïve sEVs. Intravenously administered m/lEVs showed a reduction in brain infarct sizes compared to vehicle-injected mice in a mouse middle cerebral artery occlusion model of ischemic stroke. We formulated binary mixtures of human recombinant HSP27 protein with EVs: EV/HSP27 and ternary mixtures of HSP27 and EV with cationic polymer poly (ethylene glycol)-b-poly (diethyltriamine): (PEG-DET/HSP27)/EV. (PEG-DET/HSP27)/EV and EV/HSP27 mixtures decreased the paracellular permeability of small and large molecular mass fluorescent tracers in oxygen glucose-deprived primary human BECs. This one-two-punch approach to increase BEC metabolic function and tight junction integrity is a promising strategy for BBB protection and prevention of long-term neurological dysfunction post-ischemic stroke.Graphical AbstractHighlightsMedium-to-large extracellular vesicles (m/lEVs), not small EVs contain mitochondriam/lEVs increased ATP and mitochondrial function in brain endothelial cells (BECs)m/lEVs from oligomycin-exposed BECs did not increase recipient BEC ATP levelsIntravenously injected m/lEVs reduced brain infarct sizes in a mouse stroke modelEV/HSP27 mixtures reduced small and large dextran molecule permeability across BECs

Thiol–ene chemistry draws much attention nowadays in the construction of functional polymer materials due to its versatility and fast reaction kinetics, though only a few studies have been reported...

Isoflavones, such as Genistein (Ge) and Daidzein (Dz) are widely studied Phytoestrogens with potent anti-osteoporotic and good antioxidant activity. Cowpea is one such legume having high isoflavone content and hence we aimed at studying the beneficial effects of the isoflavones isolated from cowpea as it is widely accepted staple food in India. Previously, we reported the effect of Cowpea isoflavones (CP) and Vitamin D (VD) owing to its ability of improving the osteoporotic condition in a diet induced osteoporotic rat model. In the present study, we tried to explore the underlying mechanism of CP and VD along with positive controls Dz and Ge in influencing the functions of human osteoblasts at cellular level. Initially, MG-63 cells were assessed for the expression of genes involved in BMP-2 signaling pathway, like Bone morphogenic protein (BMP-2), transcription factor Osterix (OSX), total and phosphorylated Smad 1/5/8 levels and osteoblast specific genes levels namely Alkaline phosphatase (ALP), Osteopontin (OPN), and Collagen by immunoblot, flow cytometry, and quantitative RT-PCR studies. All the levels that were upregulated with the initial exposure of the compounds got inhibited after Noggin exposure a specific BMP-2 antagonist both at protein level and m-RNA level, except OSX where the expression was totally hindered in CP and Ge treated groups alone. Hence, CP and VD activate BMP-2/Smad signaling pathway and promote further proliferation and differentiation of osteoblasts. Therefore, results prove that isoflavones isolated from cowpea could be used in treating bone-related disorders.

Nanoporous silica membranes exhibit excellent H2/CO2 separation properties for sustainable H2 production and CO2 capture but are prepared via complicated thermal processes above 400 oC, which prevent their scalable production at low cost. Here, we demonstrate the rapid fabrication (within 6 minutes) of ultrathin silica membranes (≈6 nm) via oxygen plasma treatment of polydimethylsiloxane based thin-film composite membranes at 20 oC. The resulting organosilica membranes exhibit H2 permeance of 280 - 930 GPU (1 GPU = 3.347×10-10 mol m-2 s-1 Pa-1) and H2/CO2 selectivity of 93 - 32 at 200 °C, far surpassing state-of-the-art membranes and Robeson’s upper bound for H2/CO2 separation. When challenged with a 3-day simulated syngas test containing water vapor and a 340-day stability test at 200 °C, the membrane shows stable separation performance. The robust H2/CO2 separation properties coupled with excellent scalability demonstrate the great potential of these organosilica membranes for economic H2 production with minimal carbon emissions.

Social isolation and loneliness are risk factors for stroke. Elderly women are more likely to be isolated. Census data shows that in homeowners over the age of 65, women are much more likely to live alone. However, the underlying mechanisms of the detrimental effects of isolation have not been well studied in older females. In this study, we hypothesized that isolation impairs post-stroke recovery in aged female mice, leading to dysregulated microRNAs (miRNAs) in the brain, including those previously shown to be involved in response to social isolation (SI). Aged C57BL/6 female mice were subjected to a 60-min middle cerebral artery occlusion and were randomly assigned to either single housing (SI) or continued pair housing (PH) immediately after stroke for 15 days. SI immediately after stroke led to significantly more brain tissue loss after stroke and higher mortality. Furthermore, SI significantly delayed motor and sensory recovery and worsened cognitive function, compared to PH. A decrease in cell proliferation was seen in the dentate gyrus of SI mice assessed by bromodeoxyuridine (BrdU) labeling. miRNAome data analysis revealed changes in several miRNAs in the brain, such as miR-297a-3p and miR-200c-3p, which are known to regulate pathways involved in cell proliferation. In conclusion, our data suggest that SI can lead to a poor post-stroke recovery in aged females and dysregulation of miRNAs and reduced hippocampal cell proliferation.

Neoantigen formation due to the interaction of drug molecules with human leukocyte antigen (HLA)-peptide complexes can lead to severe hypersensitivity reactions. Flucloxacillin (FLX), a β-lactam antibiotic for narrow-spectrum gram-positive bacterial infections, has been associated with severe immune-mediated drug-induced liver injury caused by an influx of T-lymphocytes targeting liver cells potentially recognizing drug-haptenated peptides in the context of HLA-B*57:01. To identify immunopeptidome changes that could lead to drug-driven immunogenicity, we used mass spectrometry to characterize the proteome and immunopeptidome of B-lymphoblastoid cells solely expressing HLA-B*57:01 as MHC-I molecules. Selected drug-conjugated peptides identified in these cells were synthesized and tested for their immunogenicity in HLA-B*57:01-transgenic mice. T cell responses were evaluated in vitro by immune assays. The immunopeptidome of FLX-treated cells was more diverse than that of untreated cells, enriched with peptides containing carboxy-terminal tryptophan and FLX-haptenated lysine residues on peptides. Selected FLX-modified peptides with drug on P4 and P6 induced drug-specific CD8+ T cells in vivo. FLX was also found directly linked to the HLA K146 that could interfere with KIR-3DL or peptide interactions. These studies identify a novel effect of antibiotics to alter anchor residue frequencies in HLA-presented peptides which may impact drug-induced inflammation. Covalent FLX-modified lysines on peptides mapped drug-specific immunogenicity primarily at P4 and P6 suggesting these peptide sites as drivers of off-target adverse reactions mediated by FLX. FLX modifications on HLA-B*57:01-exposed lysines may also impact interactions with KIR or TCR and subsequent NK and T cell function.

Purpose: The main aim of the present investigation was to enhance the solubility of poorly soluble Gliclazide by nanocrystallization. Methods: In present investigation gliclazide nanocrystals were prepared by sonoprecipitation using Pluronic F68, Poly Vinyl Alcohol (PVA), Poly ethylene Glycol 6000 (PEG), Poly Vinyl Pyrrolidine (PVP K30) and Sodium Lauryl Sulphate (SLS) as stabilizers. Fourier Transform Infrared Spectroscopic study (FTIR), Differential Scanning Calorimetry (DSC) and X ray diffraction (XRD) studies were conducted to study the drug interactions. Size and zeta potential of the nanocrystals were evaluated. In vitro and in vivo studies of nanocrystals were conducted in comparison to pure gliclazide. Results: The Gliclazide nanocrystals (GN) showed mean particle size of 131±7.7 nm with a zeta potential of -26.6 mV. Stable nanocrystals were formed with 0.5% of PEG 6000. FTIR, DSC and XRD studies of nanocrystals showed absence of interactions and polymorphism. SEM photographs showed a change in morphology of crystals from rod to irregular shape. There is an increase in the saturation solubility and the percentage drug release from formulation GN5 (Optimized Gliclazide Nanocrystals) was found to be 98.5 in 15 min. In the in vivo study, GN5 nanocrystals have reduced the blood glucose level to 296.4±4.26 mg/dl in 12 hr. The nanocrystals showed lower tmax and higher Cmax values as compared to pure gliclazide. Conclusion: The prepared nanocrystals of gliclazide were stable without any drug polymer interactions. Increase in the dissolution of nanocrystals compared to pure gliclazide and significant reduction in blood glucose level in vivo indicated better bioavailability of the nanocrystals. Therefore, it is concluded that nanocrystal technology can be a promising tool to improve solubility and hence dissolution of a hydrophobic drug.

Two different highly cross-linked benzimidazole linked polymers (BILPs) displaying high surface area were successfully incorporated into Matrimid polymer to form a series of new mixed matrix membranes (MMMs). The surface functionality of the BILPs, BILP-4 and BILP-101, were exploited to assure the interaction with the Matrimid matrix and produce robust MMMs, which displayed significantly improved CO2 gas permeability. The ideal selectivities for CO2/N2 were calculated with enhancements as high as 34% at 15 wt% BILP loading. While BILP-4 and BILP-101 have similar structures and functionality, the two materials have notably different surface areas and CO2 adsorption capacity. Despite the differences in their gas adsorption properties, MMMs composed of Matrimid/BILP-4 and Matrimid/BILP-101 had very similar gas transport properties. These results suggest that the functional groups of the filler particle and the resulting interaction with the polymer matrix may have had more influence on the gas separation properties of the mixed matrix membrane than the adsorption properties of the fillers.

Zwitterionic materials have been widely used to modify membrane surfaces to increase surface hydrophilicity and mitigate fouling, which would otherwise decrease water permeance. However, zwitterionic materials are water-soluble, and it is challenging to graft or coat zwitterions for long-term underwater operation. In this work, we demonstrate a facile two-step coating of membrane surface using a novel zwitterionic copolymer that contains thiol groups, which is achieved using bioadhesive polydopamine (PDA) as the intermediate layer. The copolymers were synthesized by reverse addition–fragmentation chain transfer (RAFT) copolymerization of phosphobetaine methacrylate (MPC) and 2-(methacryloyloxy) ethyl lipoate (MAEL), followed by reducing the MAEL units of the resulting copolymers to dithiol-containing units (i.e., DTMAEL). While strongly bound to the membrane surface, PDA reacted with the thiol groups through Michael addition reaction to covalently graft the zwitterionic polymer (p(MPC160-co-DTMAEL42) or P...

Mixed matrix membranes (MMMs) were prepared by incorporating 10 wt%, 20 wt% and 30 wt% silica gel filler particles into novel ionic cross-linked polyether (IXPE) polymers. Porous silica gel has the advantage of high surface area that can increase the free volume and permeability in a polymer film while also being commercially available and low cost. The MMMs featured high chemical and thermal stability as well as a modest improvement in storage modulus. These features are due to the excellent interfacial interaction between silica gel filler particles and the polymer matrix. Increasing the loading of silica gel particles in MMMs resulted in higher permeability up to 120 Barrer for CO 2 , which is about 40% higher than the neat polymer matrix. Most importantly, the MMMs maintained a very high CO 2 /N 2 selectivity performance of around 41 for all particle loadings that were tested.

Tumor angiogenesis and PI3K/Akt/mTOR pathway are two major molecular objectives for the treatment and management of breast cancer. Here we first time report the molecular mechanism of a marine sponge alkaloid derivative 4-chloro fascapysin (4-CF) for its anticancer and antiangiogenesis potential. It simultaneously targets multiple cancer and angiogenesis dynamics, such as proliferation, chemotaxis cell migration, and invasion, growth factors signaling cascade, autophagy and apoptosis in HUVEC and MDAMB-231 breast cancer cells. It inhibited the VEGF mediated microvessel sprouting and blood vessel formation in the matrigel plug of C57/BL6J mice. It inhibits the tumor growth in ET (solid) mouse tumor model. It significantly inhibited cell survival through PI3K/Akt/mTOR pathway, with attendant effects on key pro-angiogenesis factors like HIF-1α, eNOS and MMP-2/9. The cytotoxicity of 4-CF was reversed by co-treatment with the VEGF and Akt inhibitors sunitinib and perifosine, respectively or by the addition of neutralizing VEGF antibodies. The apoptotic potential of 4-CF was through mitochondrial dependent as illustrated through loss of mitochondrial membrane potential. The safety profile of 4-CF was acceptable as it exhibits five times high cytotoxic IC50 value in normal cells as well as no apparent toxicities in experimental tumor mice at therapeutic doses.

Polymeric membranes for wastewater reuse are often fouled by suspended solids and dissolved organic matters, resulting in a dramatic decrease in water flux. Fouling can be mitigated by enhancing hydrophilicity of the membrane surface to avoid favorable interactions between the membranes and foulants. However, the modification of the membrane surface is often complicated and difficult to integrate into industrial membrane production processes. Herein we demonstrate a facile one-step coating of superhydrophilic zwitterions on the surface of ultrafiltration (UF) membranes by codepositing dopamine and sulfobetaine methacrylate (SBMA). In the presence of oxygen, dopamine forms polydopamine (PDA) adhering onto the membrane surface and anchors SBMA via Michael addition to form a robust thin superhydrophilic layer, as confirmed by contact angle measurement and X-ray photoelectron spectroscopy (XPS). The modified UF membranes demonstrate up to 80% higher water flux than the uncoated ones, when tested with water co...

A constant pressure, mixed gas permeation testing skid was deployed at the National Carbon Capture Center to test membrane performance when continuously exposed to slipstream post-combustion flue gas. Small, laboratory scale membranes can be loaded for testing and the degree of automation allowed the skid to be run unattended for several weeks at a time. In this report, we share our experience in commissioning the skid and quantifying CO2, N2 and O2 permeances of several membranes during the first round of testing. Dense films of polydimethylsiloxane and poly(bistrifluoroethoxyphosphazene) were tested with flue gas for approximately 20 h each. In addition, we successfully tested four thin film composite hollow fiber membranes made by a dip coating process, consisting of porous Torlon hollow fibers coated with a selective layer of poly(bistrifluoroethoxyphosphazene) or its mixed matrix with a metal organic framework SIFSIX-Cu-2i filler particles. Initial results suggest the polydimethylsiloxane showed comparable results to the literature data, but the coated hollow fiber membranes have lower CO2 permeances relative to N2 or O2 permeances compared to their performance under idealized, dry, contaminant-free mixed gas conditions. While quantification of H2O permeance was performed, we found it was affected by concentration polarization even with small membrane area and a low stage cut.

Interpenetrated metal organic framework (MOF) Cu(dpa)2SiF6-i (dpa = dipyridyl acetylene) with 6-coordinate copper takes up CO2 with isosteric heat of sorption Qst ≅ 40 kJ/mol, comparable to MOFs designed to have specific, strong chemisorption interactions. Although small pore size contributes to this high Qst, any preferred microscopic physisorption mechanisms were incompletely understood. We present in situ X-ray absorption spectroscopy results sensitive to local electronic structure around copper, fluorine, and nitrogen to look for signatures of CO2 interaction with and near ionic species in Cu(dpa)2SiF6-i. No changes in F or N K edge spectra imply no structural or electronic distortions to SiF62– or dpa molecules on CO2 uptake. Cu L2,3 edge spectra confirm Cu2+ valence and show weak systematic CO2-induced effects that result from distortions of the copper coordination shell. We suggest that electrostatic interaction between Cu2+ and axially aligned CO2 quadrupole moments contributes to the large Qst.

Protein carbonylation is an irreversible modification of Lys, Arg, Thr and Pro amino acids under conditions of oxidative stress. Previous studies have reported specific carbonylated residues in purified recombinant albumins, albeit with a lack of agreement between the studies. Currently, structural factors that determine site-specific protein carbonylation are not well understood. In this study, we utilized metal-catalyzed oxidizing conditions to generate carbonylation in recombinant human serum albumin (HSA) and granulocyte-colony stimulating factor (G-CSF), two proteins with distinct metal-binding abilities. To estimate predictability of HSA carbonylation sites, the same oxidative reaction was repeated based on the previously reported conditions. For G-CSF, oxidative conditions were gradually adjusted to achieve substantial levels of protein carbonylation. Corresponding accumulation of specific oxidized residues was identified and confirmed with high-resolution mass spectrometry. Our HSA dataset contained 55 carbonylated residues and showed a significant overlap with the previously published pooled data, indicating a certain level of carbonylation site specificity for albumins. Oxidation of G-CSF under multiple oxidative conditions consistently showed a highly specific carbonylation at position Pro45. We also detected a previously unreported, oxidation-induced cleavage site in G-CSF between His44 and Pro45, which might be attributed to a presence of a potential metal-binding site near residue Pro45. Our results show distinct patterns of protein carbonylation for HSA and G-CSF. Thus, specificity of protein carbonylation induced by metal-catalyzed oxidation is protein dependent and might be predicted by availability of transition metal binding site(s) within the protein.

Background: Stroke is the second leading cause of death after ischemic heart disease and the third leading cause of disability-adjusted life-years lost worldwide. There is a great need for developing more effective strategies to treat stroke and its resulting impairments. Among several neuroprotective strategies tested so far, the kynurenine pathway (KP) seems to be promising, but the evidence is still sparse. Methods: Here, we performed a systematic review of preclinical and clinical studies evaluating the involvement of KP in stroke. We searched for the keywords: (“kynurenine” or “kynurenic acid” or “quinolinic acid”) AND (“ischemia” or “stroke” or “occlusion) in the electronic databases PubMed, Scopus, and Embase. A total of 1,130 papers was initially retrieved. Results: After careful screening, forty-five studies were included in this systematic review, being 39 pre-clinical and six clinical studies. Despite different experimental models of cerebral ischemia, the results are concordant in implicating the KP in the pathophysiology of stroke. Preclinical evidence also suggests that treatment with kynurenine and KMO inhibitors decrease infarct size and improve behavioral and cognitive outcomes. Few studies have investigated the KP in human stroke, and results are consistent with the experimental findings that the KP is activated after stroke. Conclusion: Well-designed preclinical studies addressing the expression of KP enzymes and metabolites in specific cell types and their potential effects at cellular levels alongside more clinical studies are warranted to confirm the translational potential of this pathway as a pharmacological target for stroke and related complications.

This study sought to investigate the cardioprotective potency and interaction of muskmelon (Cucumis melo) with enalapril (ENA) against myocardial damage caused by acute and chronic isoprenaline (ISO) treatments in rats. In the acute model, 150 mg/kg (s.c) of ISO was administered for two consecutive days at the end of pretreatment with either ENA, muskmelon, or both in their respective groups. ISO was introduced into the chronic therapy of ENA/muskmelon/ENA + muskmelon groups during the last 10 days at 3 mg/kg. Muskmelon was tested at three doses (100, 200, and 500 mg/kg, p.o., 30 days), and one normal dose of ENA (10 mg/kg) was used. Blood samples were taken at the end of treatment, and the animals were sacrificed. Biochemical markers such as LDH and CK-MB, as well as antioxidant (superoxide dismutase (SOD) and catalases) and thiobarbituric acid reactive species (TBARS) were measured in both serum and heart tissue homogenate (HTH). To confirm the biochemical findings, histological slides of heart tissue were prepared. ISO administration induced an elevation in the amount of TBARS, which was increased in all groups in which it was administered. Prior treatment with muskmelon and ENA in animals resulted in a rise in biomarker activity in homogenated heart tissue and a decrease in serum. In terms of alleviating the abnormal conditions caused by ISO, the group given a high dose of muskmelon and combined therapy had the best outcomes. The activities of SOD and catalase were substantially higher in the treated classes. Histological findings showing the cytoprotective actions of the high dose of muskmelon and ENA have confirmed the biochemical outcomes of both models. It is therefore concluded that the high dose of muskmelon (500 mg/kg) has a promising cardioprotective potential that is improved more efficiently in the acute injury model in the presence of ENA.

Cryopreservation of immature testis is a feasible approach for germplasm preservation of male animals. Combinations of dimethyl sulfoxide (DMSO) and foetal bovine serum (FBS) are used for testis cryopreservation. However, an alternative to FBS is needed, because FBS is expensive. Buffalo ocular fluid (BuOF), a slaughter house by-product, could be an economical option. The objective of the present study was to assess whether BuOF can replace FBS for cryopreservation of immature mouse (Mus musculus), rat (Rattus norvegicus), and buffalo (Bubalus bubalis) testes. Results showed that rodent and buffalo testes frozen in DMSO (10% for rodents and 20% for buffalo) with 20% FBS or BuOF had similar numbers of viable and DNA-damaged cells (P 0.05). The expression of cell proliferation- (PCNA) and apoptosis-specific proteins (Annexin V and BAX/BCL2 ratio) were also comparable in mouse and buffalo testes frozen in DMSO with FBS or BuOF (P 0.05). Interestingly, rat testis frozen in DMSO with BuOF had lower expression of Annexin V protein than testis frozen in DMSO with FBS (P 0.05). The percentage of meiotic germ cells (pachytene-stage spermatocytes) in xenografts from testis frozen either in DMSO with BuOF or FBS did not significantly differ in rats or buffalo (P 0.05). These findings provide evidence that BuOF has potential to replace FBS for cryopreservation of immature rodent and buffalo testis. Further investigation is needed to explore whether BuOF can replace FBS for testis cryopreservation of other species.

Ketamine has been used safely in clinics for decades for analgesia and anesthesia. It is increasingly popular in clinical practice due to its new uses and importance for emergency procedures. It is known that ketamine is sequestered in the bone marrow and the major receptors for ketamine, noncompetitive N-methyl-d-aspartate receptors (NMDARs), are expressed in osteoclasts (OCs) and osteoblasts. However, the impact of ketamine on OCs or osteoblasts is unknown. In this study, we investigated the effects of ketamine on osteoclastogenesis and regulation of NMDARs expression in vitro. Bone marrows (BMs) or bone marrow macrophages (BMMs) were cultured in the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL) with or without ketamine for up to 6 days. OC formation peaked at day 5. On day 5 of culture, ketamine inhibited OC formation from both BM and BMM cultures at clinically relevant concentrations (3-200 µM). Ketamine inhibited RANKL-induced expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) in BMM cultures. Inhibition of ketamine on RANKL-induced osteoclastogenesis is associated with down-regulation of NMDARs. In addition, ketamine significantly inhibited the M-CSF induced migration of BMMs, inhibited cell fusion and significantly increased mature OC apoptosis. We conclude that clinically relevant concentrations of ketamine inhibit OC formation in both BM and BMM cultures in vitro through inhibiting migration and fusion process and enhancing mature OC apoptosis. It is likely that ketamine regulates osteoclastogenesis, at least in part, via its effects on NMDAR expression. J. Cell. Biochem. 118: 914-923, 2017. © 2016 Wiley Periodicals, Inc.

International audience; A series of cross-linked polyether-based 1,2,3-triazolium ion conducting membranes are prepared via the combination of thermally promoted Huisgen 1,3-dipolar cycloaddition of a dialkyne and a diazide poly(trimethylene ether glycol) monomers with in-situ N-alkylation of the resulting poly(1,2,3-triazole)s with varying contents of 1,10-diiododecane as cross-linking agent. The resulting free-standing membranes have T(g)s below -60 degrees C, T(d)s up to 230 degrees C, and Young's modulus up to 4.2 MPa. The overall combined reaction kinetics were studied by DSC yielding an activation energy of 76 kJ/mol by the Kissinger method. These ion conducting membranes have conductivities up to 10(-6) S/cm at 30 degrees C under anhydrous conditions. They have potential to be used in CO2 separation applications as they exhibit CO2 permeability of 59-110 Barrer and CO2/N-2 selectivity of 25-48.

Interfacial structures of polymer matrix-filler particle composites play a crucial role in determining the properties of the composite materials, such as the gas separation performance of mixed matrix membranes. Monte Carlo simulations employing coarse-graining models show that the density distribution and the fraction of free volume of the polymer at the interface are dominated by the interaction of the polymer with the filler particle and the geometry of the filler particle surface. Here, we studied two different filler particles with smooth and brush-like (rough) surfaces and three different polymer chains with rigid, medium and soft flexibility. Five different interaction strengths between the polymers and filler particles were studied. The polymer chains deform into pancake-like conformations on the filler particle surface in all the cases. Interestingly, the polymer chains are deformed more on the surfaces of particles that have strong repulsion in comparison to attractive and neutral surfaces. Filler particles that have brush-like surfaces tend to results in larger free volume at the interface than occurs with smooth surfaced filler particles. By contrast, the rigidity of the polymer chain introduced by considering the angle potential in the coarse-grain model only slightly influences the chain conformation at the interface.

Aging is associated with cognitive decline and decreased concentrations of short-chain fatty acids (SCFAs) in the gut. SCFAs are significant in that they are protective to the gut and other organs. We tested the hypothesis that the aged gut microbiome alone is sufficient to decrease SCFAs in the host and produce cognitive decline. Fecal transplant gavages (FTGs) from aged (18–20 months) or young (2–3 months) male C57BL/6 mice into germ-free male C57BL/6 mice (N = 11 per group) were initiated at ~3 months of age. Fecal samples were collected and behavioral testing was performed over the study period. Bacterial community structures and relative abundances were measured in fecal samples by sequencing the bacterial 16S ribosomal RNA gene. Mice with aged and young microbiomes showed clear differences in bacterial β diversity at 30, 60, and 90 d (P = .001 for each) after FTGs. The fecal SCFAs, acetate, propionate, and butyrate (microbiome effect, P

Summary Mixed-matrix membranes have great potential for post-combustion carbon capture. To make membrane-based carbon capture economically viable, new formulations with high selectivity and CO2 permeance must be identified. We demonstrate here the ability to break the permeability-selectivity trade-off by using multicomponent mixed-matrix membranes (McMMMs) with two, three, or four components. Each of these components has a specific function and is designed for compatibility and high separation performance. A highly permeable polymer of intrinsic microporosity, PIM-1, and a CO2-selective polyphosphazene polymer, MEEP80, are chosen as polymer matrices. Chemical interaction between MOF nanoparticles and polymers is a key factor for optimizing the MOF-polymer interfacial compatibility. The systematic study of the impact of MOF pore size and the binding site is investigated to produce 10 different composite membranes. The permeability-selectivity values surpass the Robeson upper bound, while the predicted cost of carbon capture is reduced, which suggests the potential of these membranes for practical CO2 separations.

Membranes with high water permeance, near-zero rejection to inorganic salts (such as NaCl and Na2SO4), and almost 100% rejection to organic dyes are of great interest for the dye desalination (the separation of dyes and salts) of textile wastewater. Herein, we prepared reduced graphene oxide membranes in a solvation state (S-rGO) with nanochannel sizes rightly between the salt ions and dye molecules. The S-rGO membrane rejects >99.0% of Direct Red 80 (DR 80) and has almost zero rejection for Na2SO4. By contrast, conventional GO or rGO membranes often have channel sizes smaller than divalent ions (such as SO42–) and thus high rejection for Na2SO4. More interestingly, high salinity in typical dye solutions decreases the channel size in the S-rGO membranes and thus increases the dye rejection, while the Na2SO4 rejection decreases because of the negatively charged surface on GO and the salt screening effect. The membranes also show pure water permeance as high as 80 L m–2 h–1 bar–1, which is about 8 times tha...

Metal organic framework (MOF)/polymer composite membranes are of interest for gas separations, as they often have performance that exceeds the neat polymer. However, traditional composite membranes, known as mixed matrix membranes (MMMs), can have complex and time-consuming preparation procedures. The MOF and polymer are traditionally prepared separately and require priming and mixing to ensure uniform distribution of particles and compatibility of the polymer–particle interface. In this study, we reduce the number of steps using an in situ MOF growth strategy. Herein, MMMs are prepared by growing MOF (UiO-66) in situ within a Matrimid polymer matrix while simultaneously curing the matrix. The gas separation performance for MMMs, prepared using this approach, was evaluated for the CO2/N2 separation and compared with MMMs made using the traditional postsynthesis mixing. It was found that MMMs prepared using both the in situ MOF growth strategy and by traditional postsynthesis mixing are equivalent in perfo...

A 40-year-old man presented with altered mentation, preceded a few days earlier by a 38°C fever and shortness of breath. He was diagnosed “....influenza A pneumonia, of the H3N2 subtype, with parainfectious...” hemorrhagic encephalitis and required intubation for hypoxia and depressed consciousness. Brain MRI showed numerous hemorrhages (figure 1). He received oseltamivir, switched to peramivir for better gut absorption. He was discharged to rehabilitation 1 month later. At 6-month follow-up (figure 2), he had residual deficits in memory and concentration. Montreal Cognitive Assessment score was 28/30. He returned to full-time work as a financial manager at 9 months, and felt subjective normal cognition at 1.5 years after onset.

Homogenous amphiphilic crosslinked polymer films comprising of poly(ethylene oxide) and polysiloxane were synthesized utilizing thiol-ene “click” photochemistry. A systematic variation in polymer composition was Carried out to obtain high quality films with varied amount of siloxane and poly(ethylene oxide). These films showed improved gas separation performance with high gas permeabilities with good CO2/N2 selectivity. Furthermore, the resulting films were also tested for its biocompatibility, as a carrier media which allow human adult mesenchymal stem cells to retain their capacity for osteoblastic differentiation after transplantation. The obtained crosslinked films were characterized using differential scanning calorimetry, dynamic mechanical analysis, thermogravimetric analysis, FTIR, Raman-IR, and small angle X-ray scattering. The synthesis ease and commercial availability of the starting materials suggests that these new crosslinked polymer networks could find applications in wide range of applications. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 1548–1557

In this paper we review research progress on metal organic framework membranes which have demonstrated ability to separate carbon dioxide from different light gases. More specifically, we focus mainly on CO 2 /N 2 , CO 2 /CH 4 , and CO 2 /H 2 , gas separations which are highly relevant compositions in flue gas treatment, natural gas purification, and hydrogen purification, respectively. We also discuss several conventional and novel strategies developed by several research groups for the continuous defect-free MOF membrane fabrication. Finally, the advantages of using MOFs in mixed matrix membranes and improvements in gas separation performances with the MOF based mixed matrix membranes are presented.

Phytoestrogens (PEs) are naturally available bioactive compounds widely available in a spectrum of sources such as plant foods and are said to exhibit estrogen-like, antioxidant, and anticancer properties. There are wide range of PE-containing sources which are usually consumed by humans such as isoflavones (IF), coumestans, and lignans. Many of the fruits, vegetables, and whole grains are known to contain PE. For example, soybeans mainly contain IF, and flaxseeds mostly contain lignans, while clover, alfalfa, and soybean sprouts are rich in coumestans. There are many factors which affect the way these compounds act in a cell type such as estrogen receptor (ER)-α and ER-β levels and the amount of co-activators and corepressors present. The proposed mechanism by which these PEs work is by exerting their antioxidant effects through the inhibition of tyrosine kinase as well as DNA topoisomerase activities and also by suppressing the process of angiogenesis. Findings from molecular, cellular, and animal studies suggest that PE may potentially confer health benefits related to colon cancer (CC) pathology. High incidence of CC might be resulted with the intake of high-calorie diet including consumption of saturated fat and practicing sedentary lifestyle, whereas PEs from fiber-rich food could serve as prophylactics. The aim of this chapter is to elucidate the mechanistic approaches of different plant-based estrogens in combating colon cancer and their possible beneficial and clinical effects and therapeutic implications.

Mixed matrix membranes (MMM) have the potential to overcome the limitations of traditional polymeric membranes for gas separation by improving both the permeability and selectivity. The most difficult challenge is accessing defect free and optimized MMM membranes. Defects are generally due to incompatible interfaces between the polymer and the filler particle. Herein, we present a new approach to modify and optimize the surface of UiO-66-NH2 based MOF particles to improve its interaction with Matrimid® polymer. A series of surface modified UiO-66-NH2 particles were synthesized and characterized using 1H NMR spectroscopy, mass spectrometry, XPS, and powder X-ray diffraction. MMMs containing surface optimized MOF particles exhibit improved thermal and mechanical properties. Most importantly, the MMMs show significantly enhanced gas separation properties; CO2 permeability was increased by ∼200% and CO2/N2 ideal selectivity was increased by ∼25%. These results confirm the success of the proposed technique to mitigate defective MOF/Matrimid® interfaces.

Modification of polyurethane by adding fillers such as bentonite can improve the physical properties of polyurethane coatings. Polyurethane synthesis is carried out using the prepolymer method by reacting toluene diisocyanate (TDI) with palm oil based polyols. Bentonite addition is used to provide heat resistance in polyurethane coating material. The concentration of bentonite used was 1.5% b / b, 3.5% b / b, and 5.5% b / b. The resulting polyol synthesis will be analyzed using FTIR to see the OH group formed. The bentonite purification process was carried out by using cetyltrimethyl ammonium bromide in bentonite solution. The target in this study is the anti-bacterial properties of the products produced. Whereas to see the characteristics carried out SEM and FTIR analysis.

The continuing discovery of broad classes of materials, such as ionic liquids, zeolites, metal–organic frameworks, and block copolymers, presents an enormous opportunity in developing materials for new applications. Polymerized ionic liquid block copolymers (PIL-BCPs) fall at the union of two already large sets of materials, and are an emerging class of materials useful in gas separation membranes, ion and electron conducting materials, and as mechanical actuators. A wide range of ionic liquid moieties can be used as pendant groups along the polymer backbone, potentially allowing for a wide variation in the resulting material properties; however in practice the range of ionic liquids explored is hindered by the need to optimize polymerization conditions for each new monomer. Here, we present a modular approach to PIL-BCP synthesis where a variety of olefin bearing cations are readily conjugated to polymers using thiol-Michael click chemistry. This approach allowed for the rapid development of a diverse material library including phase separated thin films, ion-gels, and liquid PIL-BCPs, with a reduced investment in synthetic time. Finally, we demonstrate that this approach identified PIL-BCPs with increased CO2 permeability relative to PILs, which could find use in carbon capture from flue gas.

Herein we demonstrate the synthesis of ZIF-8 membranes via secondary seeded growth on tubular stainless steel porous supports. The membranes were characterized and evaluated for the separation of CO2/N2 and N2/CH4 gas mixtures. The adsorbate polarizability correlated with the adsorption capacity on ZIF-8, and the amounts of gases adsorbed were in the order: CO2 > CH4 > N2. The CO2/N2 separation selectivity’s for the ZIF-8 membranes were close to the Knudsen selectivity, suggesting that Knudsen diffusion through non-ZIF pores dominated the separation. On the other hand, the separation selectivity’s for N2/CH4 were slightly higher than the Knudsen selectivity, indicating that the flow contribution from the ZIF pores favored the transport of N2 over CH4.

The bicyclic pyran thiolone tetrahydro-3αH-[1,3]dithiolo[4,5-β]pyran-2-thione (3a) engages in a highly unusual fragmentation in the presence of DDQ. The pyran thiolone, 3a, was synthesized by chlorination of 3,4-dihydro-2H-pyran (1), followed by condensing with CS2 and NaSH. Reaction of 3a with DDQ generates the isomerized pyran thiolone tetrahydro-3αH-[1,3]dithiolo[4,5-β]pyran-2-thione (3b) and 4-benzyl-5-(3-hydroxypropyl)-1,3-dithiole-2-thione (4) via a deep-seated rearrangement. The identity of 3b was confirmed by single crystal X-ray analysis: P21/c, a=5.807(9) A, b = 12.99(2) A, c = 11.445(15), β=113.23(6)°. Mechanistic experiments and computational insight is used to explain the likely sequence of events in the highly unusual formation of 4. Collectively, these results establish fundamental reactivity patterns for further research in this area.

This study presents the fabrication of a new mixed matrix membrane using two microporous polymers: a polymer of intrinsic microporosity PIM-1 and a benzimidazole linked polymer, BILP-101, and their CO2 separation properties from post-combustion flue gas. 17, 30 and 40 wt% loadings of BILP-101 into PIM-1 were tested, resulting in mechanically stable films showing very good interfacial interaction due to the inherent H-bonding capability of the constituent materials. Gas transport studies showed that BILP-101/PIM-1 membranes exhibit high CO2 permeability (7200 Barrer) and selectivity over N2 (15). The selected hybrid membrane was further tested for CO2 separation using actual flue gas from a coal-fired power plant.

Retinal vasculopathy with cerebral leukodystrophy (RVCL) is a rare, autosomal dominant condition caused by mutations of the three-prime repair exonuclease-1 (TREX1). The phenotypic expressions range from isolated retinal involvement to varying degrees of retinopathy, cerebral infarction with calcium depositions, nephropathy, and hepatopathy. We report a case of RVCL caused by a novel TREX1 mutation. This patient’s multisystem presentation, retinal involvement interpreted as “retinal vasculitis”, and improvement of neuroimaging abnormalities with dexamethasone led to the accepted diagnosis of a rheumatologic disorder resembling Behçet’s disease. Clinicians should consider RVCL in any patient with retinal capillary obliterations associated with tumefactive brain lesions or nephropathy.

Peptide loading of major histocompatibility complex class I (MHC-I) molecules is central to antigen presentation, self-tolerance, and CD8(+) T-cell activation. TAP binding protein, related (TAPBPR), a widely expressed tapasin homolog, is not part of the classical MHC-I peptide-loading complex (PLC). Using recombinant MHC-I molecules, we show that TAPBPR binds HLA-A*02:01 and several other MHC-I molecules that are either peptide-free or loaded with low-affinity peptides. Fluorescence polarization experiments establish that TAPBPR augments peptide binding by MHC-I. The TAPBPR/MHC-I interaction is reversed by specific peptides, related to their affinity. Mutational and small-angle X-ray scattering (SAXS) studies confirm the structural similarities of TAPBPR with tapasin. These results support a role of TAPBPR in stabilizing peptide-receptive conformation(s) of MHC-I, permitting peptide editing.

Ischemic preconditioning (IPC) induces endogenous neuroprotection from a subsequent ischemic injury. IPC involves downregulation of metabolic pathways. As adenosine 5'-monophosphate-activated protein kinase (AMPK) is a critical sensor of energy balance and plays a major role in cellular metabolism, its role in IPC was investigated. A brief 3-min middle cerebral artery occlusion (MCAO) was employed to induce IPC in male mice 72 h before 90-min MCAO. Levels of AMPK and phosphorylated AMPK (pAMPK), the active form of the kinase, were assessed after IPC. A pharmacological activator or inhibitor of AMPK was used to determine the dependence of IPC on AMPK signaling. Additionally, AMPK-α2 null mice were subjected to IPC, and subsequent infarct damage was assessed. IPC induced neuroprotection, enhanced heat shock protein-70 (HSP-70), and improved behavioral outcomes. These beneficial effects occurred in parallel with a significant inhibition of pAMPK protein expression. Although both pharmacological inhibition of AMPK or IPC led to neuroprotection, IPC offered no additional protective effects when co-administered with an AMPK inhibitor. Moreover, pharmacological activation of AMPK with metformin abolished the neuroprotective effects of IPC. AMPK-α2 null mice that lack the catalytic isoform of AMPK failed to demonstrate a preconditioning response. Regulation of AMPK plays an important role in IPC-mediated neuroprotection. AMPK may be a potential therapeutic target for the treatment of cerebral ischemia.

Migration of both uninfected and infected monocytes into the brain during acute HIV infection likely initiates metabolic changes that can be observed with magnetic resonance spectroscopy (MRS). Herein, we measured changes in brain metabolism during the first year of HIV infection and examined the relationship of these metabolite levels to CD16+ monocyte populations measured in the blood. MRS was performed on nine HIV+ subjects identified during acute HIV infection and nine seronegative control subjects. HIV+ subjects were examined within 90 days of an indeterminate Western blot, then again 2 and 6 months later, during early infection. Blood samples were collected for plasma viral RNA and monocyte subset quantification. HIV+ subjects were identified with acute viral ailment and did not display severe cognitive deficits such as dementia or minor cognitive motor disorder. Changes in lipid membrane metabolism (choline levels) in the frontal cortex and white matter were observed during the initial year of HIV infection. Greater numbers of CD16+ monocytes were associated with lower N-acetylaspartate levels and higher choline levels in the brain. These results suggest that HIV infection induces metabolic changes in the brain early during infection and that these changes may be related to monocyte dynamics in the periphery.

SAPO-34 seeds and membranes were functionalized with several organic amino cations, such as ethylenediamine, hexylamine, and octylamine. The successful incorporation of the amino groups in the SAPO-34 framework was confirmed by Fourier transform infrared (FTIR) and X-ray photoemission (XPS) spectroscopies. The resultant SAPO-34 membranes were evaluated for the separation of CO2/CH4 and CO2/N2 gas mixtures. CO2/CH4 selectivities as high as 245, with CO2 permeances of ∼5 × 10(-7) mol m(-2) s(-1) Pa(-1) at 295K and 138 kPa, were observed for an optimum ethylenediamine-functionalized membrane, which corresponded to a ∼40% increase in the separation index, as compared to the nonfunctionalized SAPO-34 membrane. Similarly, the CO2/N2 separation performance was highly improved with the incorporation of ethylenediamine. CO2/N2 selectivities as high as 39, with CO2 permeances of ∼2.1 × 10(-7) mol m(-2) s(-1) Pa(-1) at 295K and 138 kPa, were observed for an optimum ethylenediamine-functionalized membrane, which corresponded to a ∼167% increase in the separation index, as compared to the nonfunctionalized SAPO-34 membrane.

We report the structural evolution of zeolitic imidazolate framework-8 (ZIF-8) as a function of time at room temperature. We have identified the different stages of ZIF-8 formation (nucleation, crystallization, growth, and stationary periods) and elucidated its kinetics of transformation. We hypothesize that the observed semicrystalline-to-crystalline transformation may take place via solution- and solid-mediated mechanisms, as suggested by the observed phase transformation evolution and Avrami's kinetics, respectively. A fundamental understanding of ZIF-8 structural evolution as demonstrated in this study should facilitate the preparation of functional metal-organic framework phases with controlled crystal size and extent of crystallinity.