Development of a Freeze-Dried Skin Care Product Composed of Hyaluronic Acid and Poly(γ-Glutamic Acid) Containing Bioactive Components for Application after Chemical Peels

Eight types of spongy sheet were prepared by freeze-drying aqueous solutions of hyaluronic acid (HA) and poly(γ-glutamic acid) (PGA) with or without bioactive components including vitamin C derivative (VC), glucosylceramide (GC), and epidermal growth factor (EGF). Spongy sheets were categorized into the following groups: Group I (HA/PGA), Group II (HA/PGA + VC), Group III (HA/PGA + GC), Group IV (HA/PGA + VC, GC), Group V (HA/PGA + EGF), Group VI (HA/PGA + VC, EGF), Group VII (HA/PGA + GC, EGF), and Group VIII (HA/PGA + VC, GC, EGF). In the first experiment, we examined fibroblast proliferation in conditioned medium that had been prepared by immersing each spongy sheet in a conventional culture medium. EGF-incorporating spongy sheets (Groups V-VIII) enhanced fibroblast proliferation more than EGF-free spongy sheets (Groups I-IV). In the second experiment, cytokine production by fibroblasts was evaluated using a wound surface model. This involved elevation of fibroblasts-incorporating collagen gel sheets to the air-liquid interface, on which a spongy sheet (Groups I, IV, V and VIII) was placed and cultured for 1 week. EGF-incorporating spongy sheets (Groups V and VIII) enhanced the production of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) by fibroblasts more than EGF-free spongy sheets (Groups I and IV). The effect of these four types of spongy sheet on wounds was investigated in animal experiments. Chemical peel was performed by contacting 50% trichloroacetic acid (TCA) on the dorsal region of mice, after which a spongy sheet was placed, and the wound condition was then observed in a two-week period. Angiogenesis was facilitated to a greater degree in Group VIII compared with Groups I, IV and V. This finding indicates that Group VIII spongy sheet is a promising aid for skin recovery after chemical peel.

Preparation and Evaluation of Poly-γ-Glutamic Acid Hydrogel Mixtures with Basic Drugs or Acidic Drugs: Effect on Ease of Swallowing and Taste Masking

The purpose of this study was to prepare a poly-γ-glutamic acid hydrogel (PGA gel), to examine its ease of swallowing using texture profile analysis (TPA) and to evaluate its taste-masking effects on basic or acidic drugs using the artificial taste sensor. Using TPA, 0.5% and 1.0% PGA gels, 0.5% and 1.0% agar and 1.0% ι-carrageenan in the absence of drug was examined the hardness, adhesiveness and cohesiveness, ranked according to permission criteria published by the Japanese Consumers Affairs Agency. 0.5% PGA gel and 1.0% agar were classified into grade II. In the taste sensor measurement, the bitterness suppressions by 0.5% PGA gel were larger than that by 1.0% agar in all drugs and the bitterness suppressions of basic drugs in 0.5% PGA gel were more potent than those of acidic drugs in 0.5% PGA gel. 1H-nuclear magnetic resonance spectroscopic analysis was carried out to examine the difference in mechanism of bitterness suppression between basic drugs and acidic drugs mixed with PGA gel. The signals of the proton nearest to the nitrogen atom of basic drugs shifted clearly upfield, suggesting an interaction between the amino group of basic drugs and the carboxyl group of PGA gel. In conclusion, PGA gel is expected to be a useful excipient in formulations contained various drugs, especially basic drugs;it also has advantage for not only increasing ease of swallowing but also masking the bitterness of drugs even though a small amount of a single drug dose might be preferred.

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.

Adsorption of La^(3+) and Ce^(3+) by poly-γ-glutamic acid crosslinked with polyvinyl alcohol

With the exploitation of rare earth ore, more and more rare earth elements came into groundwater, caused waste of resources and toxicity to the organisms. This study aimed to find an efficient adsorption material to mitigate the above issue. Through doping polyvinyl alcohol with poly-γ-glutamic acid, an immobilised PSP gel particle was produced and had the adsorption rate of La3＋ up to 97.10%. The factors including initial concentration of La3＋ or Ce3＋, adsorbent dosage, pH and temperature of the solution, which potentially affected the adsorption rate and were studied in batch mode. It was found that the optimum adsorption conditions were composed of 50 mg/L La3 VCe3＋ of initial concentration, 600 mg/L （dry mass） biomass for adsorption, pH 6, temperature 30 ℃, 150 r/min rotational speed, and 1 h adsorption time. The selective adsorption of 15 different rare earth ions in mixed aqueous solu- tions were investigated. However, no significant selective differences were observed. Scanning electron microscopy showed that the morphological characteristic of the novel gel was its porous structure, while polyvinyl alcohol gel had a compact structure. Fourier transform infrared spectroscopy suggested that carboxyl groups in the poly-γ-glutamic acid might played a key role in the adsorption process. The adsorption mechanism forecasted to be cation exchange between -COOH and R3＋. The adsorption kinetic and thermodynamic process for La3＋ and Ce3＋ was consistent with the pseudo-second-order equation and Langmuir adsorption isotherm model. It demonstrated that PSP gels particles were useful for removing REEs from wastewater.

Enhanced production of poly-γ-glutamic acid via optimizing the expression cassette of Vitreoscilla hemoglobin in Bacillus licheniformis

Poly-γ-glutamic acid(γ-PGA)is a natural polymer with various applications,and its high-viscosity hinders ox-ygen transmission and improvement of synthesis level.Vitreoscilla hemoglobin(VHB)has been introduced into various hosts as oxygen carrier,however,its expression strength and contact efficiency with oxygen hindered efficient oxygen transfer and metabolite synthesis.Here,we want to optimize the expression cassette of VHB for γ-PGA production.Firstly,our results implied that γ-PGA yields were enhanced when introducing twin-arginine translocation(Tat)signal peptides(SP_(YwbN),SP_(PhoD) and SP_(TorA))into VHB expression cassette,and the best per-formance was attained by SP YwbN from Bacillus subtilis,theγ-PGA yield of which was 18.53% higher than that of control strain,and intracellular ATP content and oxygen transfer coefficient(K_(L)a)were increased by 29.71% and 73.12%,respectively,indicating that VHB mediated by SP YwbN benefited oxygen transfer and ATP generation forγ-PGA synthesis.Furthermore,four promoters were screened,and P vgb was proven as the more suitable promoter for VHB expression andγ-PGA synthesis,andγ-PGA yield of attaining strain WX/pPvgb-YwbN-Vgb was further increased to 40.59 g/L by 10.18%.Finally,WX/pPvgb-YwbN-Vgb was cultivated in 3 L fermentor for fed-batch fermentation,and 46.39 g/Lγ-PGA was attained by glucose feeding,increased by 49.26%compared with the initial yield(31.01 g/L).Taken together,this study has attained an efficient VHB expression cassette for oxygen transfer andγ-PGA synthesis,which could also be applied in the production of other metabolites.

Electrostatic assembly functionalization of poly(γ-glutamic acid)for biomedical antibacterial applications

Poly(γ-glutamic acid)(γ-PGA)has been found widespread applications in biomedical field because of its excellent water solubility,biocompatibility,and bioactivity.Herein,a water-insoluble γ-PGA antibacterial compound is facilely fabricated via one-pot electrostatic assembly of γ-PGA with cationic ethyl lauroyl arginate(ELA).The functionalized γ-PGA compound(γ-PGA-ELA)ethanol solution can facilely produce colorless and transparent coatings on various inorganic,metal,and polymeric substrates,especially for the lumen of slender catheters(length up to 2 m,and inner diameter down to 1 mm).The functionalized γ-PGA coating presents remarkable antibacterial efficacy in vitro and in vivo.In addition,the γ-PGA compound is used as antibacterial additives of polyolefin via melting extrusion,and the asprepared antibacterial polyolefin demonstrates advantageous antibacterial efficacy.More importantly,the functionalized γ-PGA coating exhibit good hemocompatibility,low cytotoxicity,and satisfactory histocompatibility.The as-proposed γ-PGA compound has a great potential to serve as a safe and multifunctional antibacterial candidate to combat biomedical devices-related infections.

Genomic and metabolomic analysis of Bacillus licheniformis with enhanced poly-γ-glutamic acid production through atmospheric and room temperature plasma mutagenesis

Poly-γ-glutamic acid is an extracellular polymeric substance with various applications owing to its valuable properties of biodegradability,flocculating activity,water solubility,and nontoxicity.However,the ability of natural strains to produce poly-γ-glutamic acid is low.Atmospheric and room temperature plasma was applied in this study to conduct mutation breeding of Bacillus licheniformis CGMCC 2876,and a mutant strain M32 with an 11%increase in poly-γ-glutamic acid was obtained.Genome resequencing analysis identified 7 nonsynonymous mutations of ppsC encoding lipopeptide synthetase associated with poly-γ-glutamic acid metabolic pathways.From molecular docking,more binding sites and higher binding energy were speculated between the mutated plipastatin synthase subunit C and glutamate,which might contribute to the higher poly-γ-glutamic acid production.Moreover,the metabolic mechanism analysis revealed that the upregulated amino acids of M32 provided substrates for glutamate and promoted the conversion between L-and D-glutamate acids.In addition,the glycolytic pathway is enhanced,leading to a better capacity for using glucose.The maximum poly-γ-glutamic acid yield of 14.08 g·L^(–1)was finally reached with 30 g·L^(–1)glutamate.

Efficient production of poly-γ-glutamic acid by Bacillus velezensis via solid-state fermentation and its application

A novel glutamate-dependent poly-γ-glutamic acid(γ-PGA)-producing strain Bacillus velezensis CAU263 isolated from Chinese traditional Douchi was evaluated.An efficient method ofγ-PGA production was performed by this strain via solid-state fermentation(SSF)using guar meal.The maximal yield ofγ-PGA reached 158.5 g/kg dry weight(DW)in 250 mL flasks and 155.1 g/kg DW in shallow tray,respectively.The molecular weight ofγ-PGA was 3.8×106 Da,the ratio of L/D-glutamic acid was 26.1%and 73.9%.Additionally,γ-PGA significantly improved the operating characteristics of wheat dough,the specific volume of bread was increased by 15.8%and the bread hardness was reduced by 44.2%owing to the addition of 0.3 g/kgγ-PGA.Thus,γ-PGA could be produced by Bacillus velezensis CAU263 at high level using guar meal and might have potential application prospect in food industry.

Preparation and Characterization of Poly(γ-glutamic acid) Hydrogels as Potential Tissue Engineering Scaffolds

In this paper, methacrylated γ-PGA（m PGA） precursor was synthesized via reaction between γ-PGA and glycidyl methacrylate（GMA）. Hydrogels from this precursor were prepared under 365 nm ultraviolet irradiation. The swelling behavior and mechanical properties were studied in detail as functions of the degree of substitution（DS）, precursor concentration, and environmental p H. Results showed that the crosslink density, swelling kinetics and mechanical properties of the hdyrogel could be tailored by adjusting the DS and concentration of the precursor as well as the environmental p H. Three-dimensional photo-encapsulation of swine cartilage chondrocytes and Live/Dead assay proved the cytocompatibility of the hydrogel.

Safety and photochemotherapeutic application of poly(γ-glutamic acid)-based biopolymeric nanoparticle

The safety of nanomaterials, a crucial consideration for clinical translation, is enhanced by using building blocks that are biologically nontoxic. Here, we used poly(γ-glutamic acid)(γ-PGA) and dopamine as building blocks of polymeric nanomaterials for carrying hydrophobic anticancer drugs. The introduction of phenylalanine onto γ-PGA enabled the resulting amphiphilic derivative of γ-PGA acid to self-assemble in the presence of the anticancer drug paclitaxel(PTX) to form PTX-encapsulated micelles.The surfaces of PTX-loaded micelles were then coated with polymerized dopamine(PDA). The PDAcoated, amphiphilic γ-PGA-based micelles(AM) carrying PTX(PDA/AM/P) exerted near-infraredresponsive photothermal effects. Near-infrared irradiation of cancer cells treated with PDA/AM/P nanoparticles produced a greater anticancer effect than that observed in other treatment groups, indicating a synergistic effect. Intravenous administration of PDA/AM/P completely ablated tumors and prevented their recurrence. Notably, the in vivo safety profile of PDA/AM/P nanoparticles allowed PTX to be delivered at a 3.6-fold higher dose than was possible with PTX solubilized in surfactant, and circumvented the side effects of the surfactant. These results support the multifunctional potential of PDA/AM for the delivery of various hydrophobic drugs and imaging dyes for safe translation of nanomaterials into the clinic.

Metal ion-binding properties of L-glutamic acid and L-aspartic acid, a comparative investigation

A comparative research has been developed for acidity and stability constants of M(Glu)1, M(Asp)2 and M(Ttr)3 complexes, which have been determined by potentiometric pH titration. Depending on metal ion-binding properties, vital differences in building complex were observed. The present study indicates that in M(Ttr) com-plexes, metal ions are arranged to the carboxyl groups, but in M(Glu) and M(Asp), some metal ions are able to build chelate over amine groups. The results mentioned-above demonstrate that for some M(Glu) and M(Asp) complexes, the stability constants are also largely determined by the affinity of metal ions for amine group. This leads to a kind of selectivity of metal ions, and transfers them through building complexes accompanied with glutamate and aspartate. For heavy metal ions, this building complex helps the absorption and filtration of the blood plasma, and consequently, the excursion of heavy metal ions takes place. This is an important method in micro-dialysis. In this study the different as-pects of stabilization of metal ion complexes regarding to Irving-Williams sequence have been investigated.

Recovery of rare-earth metal neodymium from aqueous solutions by poly-γ-glutamic acid and its sodium salt as biosorbents:Effects of solution pH on neodymium recovery mechanisms

For recovery of metals from low-concentration sources, biosorption is one of promising technologies and poly-γ-glutamic acid（γ-PGA） has been known as a potential biosorbent for recovery of heavy metals from aqueous solutions. Effects of solution pH on recovery of rare-earth metal Nd are systematically examined to clarify mechanisms of Nd recovery by y-PGA and its sodium salt（y-PGANa）. The recovery efficiency of Nd by y-PGA increases from 2.4 to 19.6% as pH increases from 2 to 4. Subsequently the Nd recovery efficiencies for y-PGA and y-PGANa remain almost constant in the range of pH from 4 to 7. For pH 〉 7 the increase in Nd recovery is significant and 100% recovery of Nd is achieved at pH 9. The pH dependency on Nd recovery by y-PGANa is similar to that by y-PGA. Contributions of adsorption and precipitation/coagulation to Nd recovery process are quantified. Whereas the adsorption dominates Nd recovery at lower pH（〈～4）, the precipitation/coagulation controls Nd recovery process for pH 〉 7. At higher pH, purple gel precipitates are observed. The maximum adsorption capacities for γ-PGA and yPGANa are 215 mg-Nd/（g-γ-PGA） at pH 4 and 305 mg-Nd/（g-y-PGANa） at pH 3, respectively. From the spectra of FT-IR and XPS, the biosorption of Nd onto y-PGA and y-PGANa via electrostatic interaction with carboxylate anions at pH 3 is verified. The Nd complexation with amide and carboxylate anion groups on γ-PGA and γ-PGANa may also contribute to the Nd recovery. The biosorption isotherms for Nd recovery by γ-PGA and γ-PGANa can be satisfactorily fitted by the Langmuir model. The thermodynamic studies suggest that the biosorptions of Nd by γ-PGA and γ-PGANa are endothermic. The utilization of γ-PGA and γ-PGANa as potential and eco-friendly biosorbents for the highly effective recovery of Nd from aqueous solution is confirmed.

Stiff-Person Syndrome Associated with Anti-Glutamic Acid Decarboxylase Autoimmune Encephalitis in a Young Woman: A Case Report

A 34-year-old female with stiff-person syndrome(SPS)is reported in this paper.She experienced short-term memory impairment and was diagnosed with anti-glutamic add decarboxylase(GAD)autoimmune encephalitis(AE)at the local hospital.However,after the treatment with intravenous immunoglobulin and highdose glucocorticoids,her symptoms unchanged.Two months later,she was admitted to our hospital due to an unstable gait and persistent leg stiffness,at which point she was diagnosed as anti-GAD AE concomitant with SPS.Her clinical symptoms improved with an increased dose of y-aminobutyric acid(GABA)-enhancing drug and plasma exchange.Anti-GAD antibody-associated AE combined with SPS is extremely rare.Treatment with GABA-enhancing drugs and appropriate immunotherapy can improve the neurological function of patients suffering from the combination of SPS and limbic encephalitis.

Decoding the nexus:branched-chain amino acids and their connection with sleep,circadian rhythms,and cardiometabolic health

The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly in elucidating the intricate connections between the circadian clock,sleep/wake,and metabolism.Consequently,the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle.They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health,paving the way for potential therapeutic interventions.

Interfacial chemistry ofγ-glutamic acid-derived block polymer binder directing the interfacial compatibility of high voltage LiNi0.5Mn1.5O4 electrode

LiNi0.5Mn1.5O4(LNMO)spinel is one of the most promising high voltage cathode candidates for lithium ion batteries(LIBs).However,owing to the instability for organic electrolytes at 5V high voltage,it exhibits continuous oxidation,leading to the formation of unstable interface and the notorious dissolution of transition metal,which prevents the successful commercialization of LNMO.Herein,on the basis of energy level simulation,we present a high voltage resistant binder shielding strategy to address the challenging interfacial issue of LiNi0.5Mn1.5O4cathode.Our strategy is to design a novel poly(γ-glutamic acid)-c-1H,1H,9H,9H-perfluoro-1,9-nonanediol(γ-PGFO)binder with superior transition metal chelating effect and well-matched energy level to guarantee fantastic interfacial compatibility.It is demonstrated that the dissolution of transition metal is significantly suppressed in the presence ofγ-PGFO binder,which excels in the literature.It is also noted that intramolecular hydrogen binding of the well-designed binder can generate powerful facial-contact binding,which is significant for a promising binder.By encapsulating this binder inside the cathode matrix,the Li Ni0.5Mn1.5O4electrode exhibits a capacity of 105.8 m Ah g^(-1)after 500cycles at 1 C with a capacity retention of 88.2%,which is significantly superior to that of polyvinylidene fluoride(PVDF)/Li Ni0.5Mn1.5O4electrode(a capacity of 82.9 m Ah g^(-1)and a capacity retention of 63.4%).The overall Coulombic efficiency ofγ-PGFO/Li Ni0.5Mn1.5O4electrode is prominently improved to be 99.1%,compared with 95.5%of PVDF counterpart.The presented results demonstrate a promising strategy of amino acid-based binder with strong transition metal chelating capability for boosting the rapid development of high voltage lithium ion battery.

Increased excitatory amino acid transporter 2 levels in basolateral amygdala astrocytes mediate chronic stress–induced anxiety-like behavior

The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.

Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is well-documented.Nevertheless,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely understudied.The release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the penumbra.Our findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma concentrations.These amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate receptors.Blocking N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during hypoxia.It is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor activation.Thus,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain injury.Understanding these pathways co uld highlight new therapeutic targets to mitigate brain injury.

Synthesis,Crystal Structure and Luminescent Properties of a Novel Zinc(II) Complex of N-Acetyl-L-glutamic Acid and Imidazole Ligands

A novel complex [Zn（Im）2（A-glu）]-0.5H2O（Im = imidazole, A-glu = N-acetyi- L-glutamic acid） has been synthesized from the reaction of A-glu with Zn（CH3COO）2·2H20 in the presence of Im at 65 ℃, and structurally characterized by single-crystal X-ray diffraction. The complex crystallizes in tetragonai, space group P43212 with a = b = 8.9078（6）, c = 43.458（6） A, C26H36N10O11Zn2, Mr = 795.39, V= 3448.3（6） A^3, De = 1.532 g/cm^3, Z = 4,μ（MoKα） = 1.461 mm^-1, F（000） = 1640, the final R = 0.0453 and wR = 0.0992. X-ray analysis reveals that the crystal structure is constructed by mixed iigands. A-glu adopts the bis-monodentate coordination mode linking two adjacent metal ions to form a one-dimensional chain. Zinc（Ⅱ） ions are four-coordinated with a distorted tetrahedral geometry. Luminescent properties of the complex have been inves- tigated.

Combretastatin A4/poly(L-glutamic acid)-graft-PEG conjugates self-assembled to nanoparticles

Combretastatin A4(CA4) possesses varying ability to cause vascular disruption in tumors,while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficacy and drug stability. A novel macromolecular conjugate of CA4(CA4-PL) was synthesized by covalent bonding of CA4 onto poly(L-glutamic acid)-graft-polyethylene glycol(PLG-g-PEG) via Yamaguchi reaction. The obtained CA4-PL was characterized by ~1H NMR, GPC, and UV methods, and the properties of the nanoparticles composed of CA4-PL, including critical aggregation concentration, size and size distribution, and morphology, were investigated. CA4-PL can self-assemble to form micelle-like nanoparticles of 80～120 nm in diameter, which may have potential to improve the blood circulation period as well as the targetability of CA4, and find applications to treat various tumors when combined with traditional chemotherapy or radio therapy.

Additive neurorestorative effects of exercise and docosahexaenoic acid intake in a mouse model of Parkinson’s disease

There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.