Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.

Poly(lactic acid)-aspirin microspheres prepared via the traditional and improved solvent evaporation methods and its application performances

Drug-loaded microspheres are significant for the development of modern pharmaceutical products. It is well known that the taken of aspirin for long-term increases the risk of serious gastrointestinal complications, therefore a controllable delivery of aspirin is of importance to lighten those side effects. In this work, poly(lactic acid)(PLA) was chosen as the carrier to prepare PLA-aspirin microspheres by using the traditional and the improved solvent evaporation methods. It was found that no matter which experimental condition was, the encapsulation efficiency of aspirin was higher by using the improved method than that of the traditional method. Specifically, when the concentration of polyvinyl alcohol = 1%(mass),the polymer concentration = 1:20, the oil/water rate = 1:2.5, PLA-aspirin microspheres were obtained via the improved method with a high yield of 82.83%(mass) and an encapsulation efficiency of 44.09%. PLAaspirin microspheres were then prepared continuously using the improved method, which further enhanced the encapsulation efficiency to 54.56%. Approximate 85% aspirin released from microspheres within 7 days. Obvious degradation which was represented by reduction on hardness was observed by soaking microspheres in PBS for 60 days. This work is of interest because it provides a continuous route to prepare PLA-aspirin microspheres continuously with a high drug encapsulation efficiency.

Effects of Processing Variables on the Morphology and Diameter of Electrospun Poly(amino acid ester)phosphazene Nanofibers

Poly[（alanino ethyl ester）0.67 （glycino ethyl ester）0.33 phosphazene] （PAGP） was synthesized, and morphology and diameter of the electrospun PAGP nanofibers were systematically evaluated by using a cool field emission scanning electron microscope （SEM） with changing the important processing variables such as applied voltage, polymeric concentration, and ambient temperature. The average diameter of PAGP nanofibers was inversely proportional to the applied voltage, but increased with the increase of solution concentration. Lower environmental temperature was unfavorable due to the nanofibers conglutination.

SYNTHESIS AND CHARACTERIZATION OF HYPERBRANCHED POLY(ESTER-AMIDE)S BASED ON GALLIC ACID AND DL-2-AMINOBUTYRIC ACID

A novel AB3-type monomer was prepared from gallic acid and DL-2-aminobutyric acid, and used for the synthesis of the biocompatible hyperbranched poly(ester-amide)s by self-polycondensation. The polymers were characterized via FTIR and NMR spectroscopy and thermal analysis, and the average degree of branching of the polymers was estimated to be 0.75. The polymers with abundant acetyl end groups were found to be amorphous with lower intrinsic viscosity, better thermal stability and excellent solubility.

Swelling acidic poly(ionic liquid)s as efficient catalysts for the esterification of cyclohexene and formic acid

Acidic poly(ionic liquid)s(PILs)with swelling ability were synthesized by free radical copolymerization of N-vinylimidazolium ionic liquids,divinylbenzene(DVB)and sodium acrylate(NaAA),and further acidification by sulfuric acid.The swelling ability of acidic PILs was greatly affected by cross-linker content and chain length of 3-alkyl-substituents on imidazolium.Cross-linked network structures could be observed from the cryogenic scanning electron microscopy(cryo-SEM)images of the swollen acidic PILs in formic acid.Acidic PILs with network structures in swollen state exhibited excellent activities in the esterification of cyclohexene and formic acid,and the catalytic activities were in positive correlation with their swelling abilities.Acidic PIL with 3-octyl-substituent and 2.5 mol%DVB(PIL-C8-2.5DVB-HSO4)had the highest swelling ability in formic acid and exhibited comparable catalytic activities with homogeneous catalysts such as sulfuric acid and p-toluenesulfonic acid.

Adsorption of Phthalic Acid Esters by Humic Acid and Its Research Progress

Humic acid is rich in highly electronegative oxygen-containing organic functional groups,so it has high reactivity and can adsorb phthalic acid ester(PAEs)in the environment to reduce the risk of environmental pollution from PAEs.In this paper,the extraction,characterization and adsorption models of humic acid were reviewed,and the research status of adsorption of PAEs by humic acid was further summarized.Based on these,the feasibility and observable application prospect of humic acid as a cheap adsorbent were analyzed.

Direct conversion of furfural to levulinic acid/ester in dimethoxymethane:Understanding the mechanism for polymerization

This study investigated the conversion of furfural to 5-hydroxymethylfurfural(HMF)and further to levulinic acid/ester in dimethoxymethane under acidic conditions,with the particular focus on understanding the mechanism for polymer formation.The results showed that furfural could react with dimethoxymethane via electrophilic substitution reaction to form HMF or the ether/acetal of HMF,which were further converted to levulinic acid and methyl levulinate.The polymerization of furfural and the cross-polymerization between dimethoxymethane and the levulinic acid/ester produced were the main side reactions leading to the decreased yields of levulinic acid/ester.Comparing to the other solvent,methanol as the co-solvent helped to alleviate but not totally inhibited the occurrences of the polymerization,as the polymerization reactions via aldol condensation did not eliminate the C=O functionalities.As a consequence,the polymerization reactions continued to proceed.Other co-solvent used such as guaiacol,dimethyl sulfoxide and acetone interfered with the transformation of furfural to HMF or aided the polymerization reactions.The polymer produced from the reactions between furfural and DMM was different from that produced from levulinic acid/ester.The former had a higher crystallinity,while the latter was more aliphatic.The DRIFTS and TG-MS studies showed that the polymer had the carboxylic group,methyl group and the aliphatic structure in the skeleton.The removal of these functionalities was accompanied by the aromatization of the polymer.The condensation of DMM with levulinic acid/ester was the key reason for the diminished production of levulinic acid/ester.

Synthesis and Properties of Lactic Acid-based Cross-linked Poly(ester-amide)

A novel lactic acid-based cross-linked poly（ester-amide） （LCPEA） was synthesized. The gel fraction of the LCPEA could be modulated by the reaction conditions and it affected the mechanical and thermal properties of the LCPEA. The tensile strength, elastic modulus and bend strength of the LCPEA of 65% gel fraction were 4.65, 136.55 and 39.63 MPa, respectively. The thermal decomposition temperature （50 wt%） of the LCPEA was around 410℃.

High-performance and robust high-temperature polymer electrolyte membranes with moderate microphase separation by implementation of terphenyl-based polymers

Acid loss and plasticization of phosphoric acid(PA)-doped high-temperature polymer electrolyte membranes(HT-PEMs)are critical limitations to their practical application in fuel cells.To overcome these barriers,poly(terphenyl piperidinium)s constructed from the m-and p-isomers of terphenyl were synthesized to regulate the microstructure of the membrane.Highly rigid p-terphenyl units prompt the formation of moderate PA aggregates,where the ion-pair interaction between piperidinium and biphosphate is reinforced,leading to a reduction in the plasticizing effect.As a result,there are trade-offs between the proton conductivity,mechanical strength,and PA retention of the membranes with varied m/p-isomer ratios.The designed PA-doped PTP-20m membrane exhibits superior ionic conductivity,good mechanical strength,and excellent PA retention over a wide range of temperature(80–160°C)as well as satisfactory resistance to harsh accelerated aging tests.As a result,the membrane presents a desirable combination of performance(1.462 W cm^(-2) under the H_(2)/O_(2)condition,which is 1.5 times higher than that of PBI-based membrane)and durability(300 h at 160°C and 0.2 A cm^(-2))in the fuel cell.The results of this study provide new insights that will guide molecular design from the perspective of microstructure to improve the performance and robustness of HT-PEMs.

Synthesis and characterization of new biodegradable thermosensitive polyphosphazenes with lactic acid ester and methoxyethoxyethoxy side groups

Two novel biodegradable thermosensitive polyphosphazenes with lactic acid ester and methoxyethoxyethoxy side groups were synthesized via the macromolecular substitution reactions of poly(dichlorophosphazene) with the sodium salt of lactic acid ester and sodium methoxyethoxyethoxide.Their structures were confirmed by ^(31)p NMR,~1H NMR,^(13)C NMR,IR,DSC,and elemental analysis.The lower critical solution temperature(LCST) behavior in water and in vitro degradation property of the polymers was investigated.The...

An Anionic Polymer Incorporating Low Amounts of Hydrophobic Residues Is a Multifunctional Surfactant. Part 2: Emulsification, Moisture Absorption, and Moisture Retention of Alkyl Esterified Poly-γ-Glutamic Acid

In the accompanying paper (Part 1), we showed that the fatty acid moiety and the acidity of the polysaccharide-backbone of a fatty acid-containing polysaccharide might be involved in its emul-sification, moisture absorption, and moisture retention abilities. In this study, we synthesized alkyl esterified poly-γ-glutamic acid (PGA) with various chain lengths and degrees of substitution of the alkyl moieties to examine how hydrophobic groups incorporated in the anionic polymer contribute to enhanced emulsification, moisture absorption, and moisture retention. With a low degree of alkylation of PGA, these abilities were drastically improved. To improve the moisture absorption of PGA, alkylation with a short chain length is effective in forming interspaces between PGA chains to trap water molecules. Hydrophobic-hydrophilic balance may also be important to improve the emulsification and moisture retention abilities of PGA alkylates. To the best of our knowledge, this is the first report of the relationship between the structure and the multifunctional abilities of an anionic polymer incorporated with a small amount of hydrophobic residue. PGA alkylates, as well as fatty acid-containing polysaccharides, have potential use as multifunctional surfactants throughout various industries.

Vinylic polymerization of Norbornenecarboxylic Acid Esters by Palladium Complexes

New thermoplastic norbornene polymers containing ester groups were prepared byvinylic polymerization of norbornene-carboxylic acid esters by Pd(Ⅱ)-based catalysts. Themonomers were obtained by Diels-Alder reaction of cyclopentadiene with acrylic acid esters(methyl and butyl) as mixtures of endo/exo (ratio 40/60)-isomers and were converted topolymers in 60%～70% conversion. The endo-isomer was less reactive than the exo-isomer.To obtain higher molecular weight the more reactive pure exo-isomer was prepared andpolymerized with the Pd (Ⅱ)-catalysts, tetrakis (acetonitrile) Pd (Ⅱ) bis (tetrafluoroborate)and (η3-allyl)Pd(Ⅱ)SbF6, in high conversion. These polymers showed high glass transitiontemperatures, high transparency and good solubility in common solvents.

Research on the Sizing Performance of Starch Grafted Poly-hydroxy Alkyl-acid Esters

Starch grafted poly-hydroxy alkyl-acid esters were prepared via graft polymerization.Different characteristics of grafted starches were tested such as viscosity,viscosity stability,adhesion as well as properties of sized yarns.Sizing performance was analyzed from the aspect of physical and chemical reactions between polymer molecules.It shows that starch grafted poly-hydroxy alkyl-acid esters have excellent sizing performance and could absolutely be used as sizes for polyester-cotton yarns.

Anticancer Activities of Substituted Cinnamic Acid Phenethyl Esters on Human Cancer Cell Lines

Caffeic acid phenethyl ester (CAPE) and sixteen substituted cinnamic acid phenethyl esters were prepared via conventional procedures in order to test their in vitro anticancer activities by either MTT assay or SRB assay on six different human cancer cell lines. The results indicated that in the concentration of 10μmol·L^-1 the lead compmuM CAPE possessed anficancer activities against human HL-60, Bel-7402, and Hela cell lines, and two other compounds possessed potent anticancer activities against Bel-7402 and Hela cell lines.

Abiotic degradation of four phthalic acid esters in aqueous phase under natural sunlight irradiation

Abiotic degradability of four phthalic acid esters （PAEs） in the aquatic phase was evaluated over a wide pH range 5-9. The PAE solutions in glass test tubes were placed either in the dark and under the natural sunlight irradiation for evaluating the degradation rate via hydrolysis or photolysis plus hydrolysis, respectively, at ambient temperature for 140 d from autumn to winter in Osaka, Japan. The efficiency of abiotic degradation of the PAEs with relatively short alkyl chains, such as butylbenzyl phthalate （BBP） and di-nbutyl phthalate （DBP）, at neutral pH was significantly lower than that in the acidic or alkaline condition. Photolysis was considered to contribute mainly to the total abiotic degradation at all pH. Neither hydrolysis nor photolysis of di-ethylhexyl phthalate （DEHP） proceeded significantly at any pH, especially hydrolysis at neutral pH was negligible. On the other hand, the degradation rate of di- isononyl phthalate （DINP） catalyzed mainly by photolysis was much higher than those of the other PAEs, and was almost completely removed during the experimental period at pH 5 and 9. As a whole, according to the half-life （t1/2） obtained in the experiments, the abiotic degradability of the PAEs was in the sequence： DINP （32-140 d） 〉 DBP （50-360 d）, BBP （58-480 d） 〉 DEHP （390-1600 d） under sunlight irradiation （via photolysis plus hydrolysis）. Although the abiotic degradation rates for BBP, DBP, and DEHP are much lower than the biodegradation rates reported, the photolysis rate for DINP is comparable to its biodegradation rate in the acidic or alkaline condition.

Identification of differential proteins in colorectal cancer cells treated with caffeic acid phenethyl ester

AIM: To investigate the molecular mechanisms of the anti-cancer activity of caffeic acid phenethyl ester(CAPE).METHODS: Protein profiles of human colorectal cancer SW480 cells treated with or without CAPE were analysed using a two-dimensional(2D) electrophoresis gelbased proteomics approach. After electrophoresis, the gels were stained with Coomassie brilliant blue R-250. Digital images were taken with a GS-800 Calibrated Densitometer, and image analysis was performed using PDQuest 2-D Analysis software. The altered proteins following CAPE treatment were further identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry following a database search. The identified proteins were validated by Western blot and immunofluorescence assay.RESULTS: CAPE induced human colorectal cancer cell apoptosis. Four up-regulated proteins and seven down-regulated proteins in colorectal cancer cells treated with CAPE were found. The identified downregulated proteins in CAPE-treated colorectal cancer cells were Triosephosphate Isomerase(Tim), Proteasome subunit alpha 4(PSMA4) protein, Guanine nucleotide binding protein beta, Phosphoserine aminotransferase 1(PSAT1), PSMA1, Myosin XVIIIB and Tryptophanyl-tRNA synthetase. Notably, CAPE treatment led to the down-regulation of PSAT1 and PSMA1, two proteins that have been implicated in tumorigenesis. The identified up-regulated proteins were Annexin A4, glyceraldehyde-3-phosphate dehydrogenase, Glucosamine-6-phosphate deaminase 1(GNPDA1), and Glutathione peroxidase(GPX-1). Based on high match scores and potential role in cell growth control, PSMA1, PSAT1, GNPDA1 and GPX-1 were further validated by Western blotting and immunofluorescence assay. PSMA1 and PSAT1 were down-regulated, while GNPDA1 and GPX-1 were up-regulated in CAPE-treated colorectal cancer cells. CONCLUSION: These differentiated proteins in colorectal cancer cells following CAPE treatment, may be potential molecular targets of CAPE and involved in the anti-cancer effect of CAPE.

Caffeic acid phenethyl ester inhibits liver fibrosis in rats

AIM: To investigate the hepatoprotective effects and antioxidant activity of caffeic acid phenethyl ester(CAPE) in rats with liver fibrosis. METHODS: A total of 75 male Sprague-Dawley rats were randomly assigned to seven experimental groups: a normal group(n = 10), a vehicle group(n = 10), a model group(n = 15), a vitamin E group(n = 10), and three CAPE groups(CAPE 3, 6 and 12 mg/kg, n = 10, respectively). Liver fibrosis was induced in rats by injecting CCl4 subcutaneously, feeding with high fat forage, and administering 30% alcohol orally for 10 wk. Concurrently, CAPE(3, 6 and 12 mg/kg) was intraperitoneally administered daily for 10 wk. After that, serum total bilirubin(TBil), aminotransferase(ALT) and aspartate aminotransferase(AST) levels were measured to assess hepatotoxicity. To investigate antioxidant activity of CAPE, malondialdehyde(MDA), glutathione(GSH) levels, catalase(CAT) and superoxide dismutase(SOD) activities in liver tissue were determined. Moreover, the effect of CAPE on α-smooth muscle actin(α-SMA), a characteristic hallmark of activated hepatic stellate cells(HSCs), and NF-E2-related factor 2(Nrf2), a key transcription factor for antioxidant systems, was investigated by immunohistochemistry. RESULTS: Compared to the model group, intraperitoneal administration of CAPE decreased TBil, ALT, and AST levels in liver fibrosis rats(P < 0.05), while serum TBil was decreased by CAPE in a dose-dependent manner. In addition, the liver hydroxyproline contents in both the 6 and 12 mg/kg CAPE groups were markedly lower than that in the model group(P < 0.05 and P < 0.001, respectively). CAPE markedly decreased MDA levels and, in turn, increased GSH levels, as well as CAT and SOD activities in liver fibrosis rats compared to the model group(P < 0.05). Moreover, CAPE effectively inhibited α-SMA expression while increasing Nrf2 expression compared to the model group(P < 0.01). CONCLUSION: The protective effects of CAPE against liver fibrosis may be due to its ability to suppress the activation of HSCs by inhibiting oxidative stress.

Synergistic extraction of rare earth by mixtures of 2-ethylhexyl phosphoric acid mono-2-ethylhexyl ester and di-(2-ethylhexyl) phosphoric acid from sulfuric acid medium

The extraction of Nd^3＋ and Sm^3＋, including the extraction and stripping capability as well as the separation effect of Nd^3＋ or Sm^3＋, from a sulfuric acid medium, by mixtures of di-（2-ethylhexyl） phosphoric acid （HDEHP, H2A2（0）） and 2-ethylhexyl phosphoric acid mono-2-ethylhexyl ester （HEH/EHP, H2L2（0）） were studied. The distribution ratios and synergistic coefficients of Nd^3＋ and Sm^3＋ in different acidities were also determined. A synergistic extractive effect was found when HDEHP and HEH/EHP were used as mixed extractants for Sm^3＋ or Nd^3＋. The chemical compositions of the extracted complex were determined as Nd.（HA2）2-HL2 and Sm.（HA2）2-HL2. The extraction equilibrium constants, enthalpy change, and entropy change of the extraction reaction were also determined.

Synthesis of the Biomimetic Polymer: Aliphatic Diamine and RGDS Modified Poly(d,l-lactic acid)

A novel poly（d, /-lactic acid） （PDLLA） based biomimetic polymer was synthesized by grafting maleic anhydride, butanediamine and arg-gly-asp-ser （RGDS） peptides onto the backbone of PDLLA, aiming to overcome the acidity and auto-accelerating degradation of PDLLA during degradation and to improve its biospecificity and biocompatibility. The synthetic copolymer was characterized by FTIR, ^13C NMR and amino acid analyzer （AAA）.

CLAY CATALYZED SYNTHESIS OF BIO-DEGRADABLE POLY(GLYCOLIC ACID)

Glycolic acid was polymerized under vacuum in the presence and absence of nano sized clay.The added clay catalyzed the condensation polymerization which can be confirmed by recording FTIR spectroscopy and intrinsic viscosity (Ⅳ)values.The relative intensity of C=O/CH is increased while increasing the amount of clay.DSC showed the appearance of multiple endotherms of poly(glycolic acid).TGA showed the percentage weight residue remain above 750℃for polymer-nano composite system was 21% and hence proved the fl...