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.

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.

Rapid, accurate and serotype independent pipeline for in silico epitope mapping of SARS-CoV-2 antigens: a combined machine learning and Chou’s pseudo amino acid composition method

Here,a new integrated machine learning and Chou’s pseudo amino acid composition method has been proposed for in silico epitope mapping of severe acute respiratorysyndrome-like coronavirus antigens.For this,a training dataset including 266 linear B-cell epitopes,1,267 T-cell epitopes and 1,280 non-epitopes were prepared.The epitope sequences were then converted to numerical vectors using Chou’s pseudo amino acid composition method.The vectors were then introduced to the support vector machine,random forest,artificial neural network,and K-nearest neighbor algorithms for the classification process.The algorithm with the highest performance was selected for the epitope mapping procedure.Based on the obtained results,the random forest algorithm was the most accurate classifier with an accuracy of 0.934 followed by K-nearest neighbor,artificial neural network,and support vector machine respectively.Furthermore,the efficacies of predicted epitopes by the trained random forest algorithm were assessed through their antigenicity potential as well as affinity to human B cell receptor and MHC-I/II alleles using the VaxiJen score and molecular docking,respectively.It was also clear that the predicted epitopes especially the B-cell epitopes had high antigenicity potentials and good affinities to the protein targets.According to the results,the suggested method can be considered for developing specific epitope predictor software as well as an accelerator pipeline for designing serotype independent vaccine against the virus.

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.

Branched-chain amino acids to tyrosine ratio value as a potential prognostic factor for hepatocellular carcinoma

The prognosis of hepatocellular carcinoma(HCC) depends on tumor extension as well as hepatic function.Hepatic functional reserve is recognized as a factor affecting survival in the treatment of HCC;the ChildPugh classif ication system is the most extensively used method for assessing hepatic functional reserve in patients with chronic liver disease,using serum albumin level to achieve accurate assessment of the status of protein metabolism.However,insuff icient attention has been given to the status of amino acid(AA) metabolism in chronic liver disease and HCC.Fischer's ratio is the molar ratio of branched-chain AAs(BCAAs:leucine,valine,isoleucine) to aromatic AAs(phenylalanine,tyrosine) and is important for assessing liver metabolism,hepatic functional reserve and the severity of liver dysfunction.Although this ratio is diff icult to determine in clinical situations,BCAAs/tyrosine molar concentration ratio(BTR) has been proposed as a simpler substitute.BTR correlates with various liver function examinations,including markers of hepatic f ibrosis,hepatic blood flow and hepatocyte function,and can thus be considered as reflecting the degree of hepatic impairment.This manuscript examines the literature to clarify whether BTR can serve as a prognostic factor for treatment of HCC.

Evolution from Primitive Life to Homo sapiens Based on Visible Genome Structures: The Amino Acid World

It is not too much to say that molecular biology, including genome research, has progressed based on the determination of nucleotide or amino acid sequences. However, these ap-proaches are limited to the analysis of relatively small numbers of the same genes among spe-cies. On the other hand, by graphical presenta-tion of the ratios of the numbers of amino acids present to the total numbers of amino acids presumed from the target gene(s) or genome or those of the numbers of nucleotides present to the total numbers of nucleotides calculated from the target gene(s) or genome, we can readily draw conclusions from extraordinarily huge data sets integrated by human intelli-gence. 1) Assuming polymerization of amino acids or nucleotides in a simulation analysis based on a random choice, proteins were formed by simple amino acid polymerization, while nucleotide polymerization to form nucleic acids encoding specific proteins needed certain specific control. These results proposed that protein formation chronologically preceded codon formation during the establishment of primitive life forms. In the prebiotic phase, amino acid composition was a dominant factor that determined protein characteristics;the “Amino Acid World”. 2) The genome is constructed homogeneou- sly from putative small units displaying similar codon usages and coding for similar amino acid compositions;the unit is a gene assembly en-coding 3,000 - 7,000 amino acid residues and this unit size is independent not only of genome size, but also of species. 3) In codon evolution, all nucleotide alterna-tions are correlated, not only in coding regions, but also in non-coding regions;the correlations can be expressed by linear formulas;y = ax + b, where “y” and “x” represent nucleotide con-tents, and “a” and “b” are constant. 4) The basic pattern of cellular amino acid compositions obtained from whole cell lysates is conserved from bacteria to Homo sapiens, and resembles that calculated from complete genomes. This basic pattern is characterized by a “star-shape” that changes slightly among species, and changes in amino acid composi-tion seem to reflect biological evolution. 5) Organisms can essentially be classified according to two codon patterns. Biological evolution due to nucleotide sub-stitutions can be expressed by simple linear formulas based on mathematical principles, while natural selection must affect species pre- servation after nucleotide alternations. There-fore, although Darwin’s natural selection is not directly involved in nucleotide alternations, it contributes obviously to the selection of nu-cleotide alternations. Thus, Darwin’s natural selection is doubtless an important factor in biological evolution.

DCHA AS A NEW REAGENT FOR THE ESTERIFICATION OF OBSTINATED AMINO ACIDS BY THE MERRIFIELD'S RESIN

The obstinated amino acid,Boc-Asn(or Boc-Gln),was directly anchored onto the Merrifield's resin using DCHA as the base in present reaction.The yield(71.88%)of Boc-Asn-OCH_2-resin was much better than those(0-33.5%)using Cs_2CO_3,KOH,KF.DEA and TEA as the base.which are efficient reagents for other amino acids in the same reaction.

Study on the synthesis of spin labeled poly(styrene-co-maleic acid)s and their segmental motion

Study of the segmental mobility of polymer chains is important when the polymer is used as drag reduction agents of crude oil.Electron spin resonance(ESR)spectroscopy can provide important information about segmental dynamics of polymer chains,which is related to their microenvironment.In this article,we employed an amphiphilic polymer to study the effect of hydrophilic/hydrophobic balance of the polymers on the segmental motion of polymer chains.Poly(styrene-co-maleic acid)(PSMA)was spin labeled with 4-amino TEMPO radicals by increasing the concentration of radical moiety on the polymer chains.The PSMA and spin labeled-PSMAs(SL-PSMAs)were characterized by nuclear magnetic resonance(NMR),Fourier transform infrared(FT-IR)spectroscopy,Cyclic voltammetry(CV)and ESR techniques.Inter-polymer complexes(IPCs)of SL-PSMA-2 were prepared by employing polyethylene glycols(PEGs)of varying molecular weights.The results showed that the increased hydrophobic interactions of nitroxide radicals on the SLPSMAs’chains reduced the rotational mobility of spin labels and the random coil-toglobular transition of polymer chains occurred at higher pH value for SL-PSMAs,which showed a slow motion component in the ESR spectra of SL-PSMAs.Further,by increasing the molecular weight of PEGs in IPCs the complexation was increased,which also reduced the rotational motion of spin labels due to interpolymer hydrogen bonding causing a slow motion component in the ESR spectra.©2021 The Authors.

Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

Therapeutic effects of Lingguizhugan decoction in a rat model of high-fat diet-induced insulin resistance

BACKGROUND Lingguizhugan(LGZG)decoction is a widely used classic Chinese medicine formula that was recently shown to improve high-fat diet(HFD)-induced insulin resistance(IR)in animal studies.AIM To assess the therapeutic effect of LGZG decoction on HFD-induced IR and explore the potential underlying mechanism.METHODS To establish an IR rat model,a 12-wk HFD was administered,followed by a 4-wk treatment with LGZG.The determination of IR status was achieved through the use of biochemical tests and oral glucose tolerance tests.Using a targeted metabolomics platform to analyze changes in serum metabolites,quantitative real-time PCR(qRT-PCR)was used to assess the gene expression of the ribosomal protein S6 kinase beta 1(S6K1).RESULTS In IR rats,LGZG decreased body weight and indices of hepatic steatosis.It effectively controlled blood glucose and food intake while protecting islet cells.Metabolite analysis revealed significant differences between the HFD and HFDLGZG groups.LGZG intervention reduced branched-chain amino acid levels.Levels of IR-related metabolites such as tryptophan,alanine,taurine,and asparagine decreased significantly.IR may be linked to amino acids due to the contemporaneous increase in S6K1 expression,as shown by qRT-PCR.CONCLUSIONS Our study strongly suggests that LGZG decoction reduces HFD-induced IR.LGZG may activate S6K1 via metabolic pathways.These findings lay the groundwork for the potential of LGZG as an IR treatment.

Free amino acid content in trunk,branches and branchlets of Araucaria angustifolia(Araucariaceae)

Araucaria angustifolia(Bertol.) O. Kuntze exhibits dimorphism in its stem structure, where the trunk is orthotropic and branches and branchlets(primary and secondary branches) are plagiotropic. These stems exhibit different behavior when used for vegetative propagation,and only segments of trunk can form a complete plant. The physiological and biochemical mechanisms that characterize these stems are still little known. The aim of this study was to describe the free amino acid profiles in trunks,branches, and branchlets of A. angustifolia. Segments of 5 cm in length were excised from young individuals below the stem apex. The needles were removed and samples were frozen and lyophilized. The determinations were made by high-performance liquid chromatography, and the results were expressed as lg/g fresh weight(FW). The trunks and branches had the highest content of total amino acids, which were 112.23 ± 20.57 lg/g FW and 111.97 ± 27.78 lg/g FW, respectively. The amino acids—glutamine, aspartate and c-aminobutyric acid and tyrosine—were noticeably higher in the three types of stems.In the trunk, a higher amount of asparagine and tryptophan,was also detected. Glutamic acid and glutamine were found in higher quantities in the branches. The branchlets had very low total amino acid content (30.79 ± 4.19 lg/g FW), wherein asparagine is the only amino acid not detected. Thus, it was observed that the profile of the free amino acid differs among trunks, branches, and branchlets in A. angustifolia, indicating that they perform different functions.

Synthesis,Characterization and Structure of Chiral Amino Acids and Their Corresponding Amino Alcohols with Camphoric Backbone

Chiral amino acids and their corresponding amino alcohols bearing camphoric backbone were prepared from D-（＋）-camphoric imide and characterized by infrared, elemental analysis, ESI-MS, and NMR measurements. Among them, one intermediate （1S,3R）-3-amino-2,2,3- trimethyl cyclopentane-1-carboxylic acid hydrochloride 3 was structurally elucidated by X-ray diffraction techniques. Versatile intermolecular hydrogen bonding interactions observed in its packing structure result in a two-dimensional framework.

Natural selection in vertebrate evolution under genomic and biosphere biases based on amino acid content: Primitive vertebrate hagfish (<i>Eptatretus burgeri</i>)

Cluster analyses using the amino acid content predicted from the coding regions (13 genes) of complete vertebrate mitochondrial genomes as traits grouped selected vertebrates into two clusters, terrestrial and aquatic vertebrates. Exceptions were the hagfish (Eptatretus burgeri), thought to be an early ancestor of vertebrates, and the black spotted frog (Rana nigromaculata), which is terrestrial as an adult and aquatic as a larva. These two species fall into the terrestrial and aquatic clusters, respectively. Using the nucleotide (G, C, T and A) content in the coding and non-coding regions, and in the complete genome as traits, similar results were obtained but with some additional exceptions. In addition, phylogenetic analyses of 16S rRNA sequences produced a consistent result. The results of this study indicated that vertebrate evolution is controlled by natural selection under both an internal bias as a result of nucleotide replacement genomic rules, and an external bias caused by environmental biospheric conditions.

PLA/PBS/PEG共混体系非等温热分解动力学

为了探究聚乳酸/聚丁二酸丁二醇酯/聚乙二醇(PLA/PBS/PEG)共混体系的热分解行为,通过熔融开炼共混法制备了PLA/PBS/PEG共混体系,利用同步热分析仪考察了不同加热速率下复合材料的热解行为。使用无模型方法Kissinger方程和Ozawa方程计算出了平均活化能,运用模型方法Coats-Redfern方程,将不同的热解机理函数带入其中,计算出活化能,将两个活化能进行对比,以明确最合适的反应模型。结果表明,该复合材料的热解机理函数为G(α)=[1-(1-α)^(-3)]/(-3),即随机成核随后生长。

猪胰脂肪酶固定化及连续流催化拆分合成(S)-2-四氢糠酸

通过筛选实验确定了树脂ESQ-3为PPL的最佳固定化载体,并确定了最佳固定化条件和固定化酶PPL@ESQ-3拆分四氢呋喃-2-甲酸丁酯(2-THFAD)的最适条件,将此固定化条件应用于连续流反应器系统并进行条件优化。实验结果表明:在该条件下,59 min即可将60 mmol 2-THFAD完全拆分得到(S)-四氢呋喃-2-甲酸丁酯((S)-2-THFAD,ee_(s)≥99%),催化效率达到3.347μmol/(min·g),催化效果远胜于间歇式反应;(S)-2-THFAD直接由Novozym 435水解得(S)-2-THFA(ee_(p)≥99%),比旋度[α]_(D)^(21)=3.542(2.0mol/L,甲醇)。PPL@ESQ-3连续流反应体系表现出了优秀的催化能力,具有适用于工业化生产(S)-2-THFA的应用潜力。

Synthesis of Poly(aryl amide imide)s Derived from o-diphenyltrimellitic Anhydride

The synthesis and characterization of a series of novel poly(aryl amide imide)s based on o diphenyltrimellitic anhydride are described.The poly(aryl amide imide)s having inherent viscosities of 0.39-1.43dL/g in N methyl 2 pyrrolidinone at 30℃,were prepared by polymerization with aromatic diamines in N,N-dimethylacetamide and subsequent chemical imidization.All the polymers were amorphous,readily soluble in aprotic polar solvents such as DMAC,NMP,DMF,DMSO,and m cresol,and could be cast to form flexible and tough films.The glass trsanition temperatures were in the range of 284-336℃,and the temperatures for 5% weight loss in nitrogen were above 468℃.

Alterations in gut microbiota are related to metabolite profiles in spinal cord injury

Studies have shown that gut microbiota metabolites can enter the central nervous system via the blood-spinal cord barrier and cause neuroinflammation, thus constituting secondary injury after spinal cord injury. To investigate the correlation between gut microbiota and metabolites and the possible mechanism underlying the effects of gut microbiota on secondary injury after spinal cord injury, in this study, we established mouse models of T8–T10 traumatic spinal cord injury. We used 16 S rRNA gene amplicon sequencing and metabolomics to reveal the changes in gut microbiota and metabolites in fecal samples from the mouse model. Results showed a severe gut microbiota disturbance after spinal cord injury, which included marked increases in pro-inflammatory bacteria, such as Shigella, Bacteroides, Rikenella, Staphylococcus, and Mucispirillum and decreases in anti-inflammatory bacteria, such as Lactobacillus, Allobaculum, and Sutterella. Meanwhile, we identified 27 metabolites that decreased and 320 metabolites that increased in the injured spinal cord. Combined with pathway enrichment analysis, five markedly differential amino acids(L-leucine, L-methionine, L-phenylalanine, L-isoleucine and L-valine) were screened out, which play a pivotal role in activating oxidative stress and inflammatory responses following spinal cord injury. Integrated correlation analysis indicated that the alteration of gut microbiota was related to the differences in amino acids, which suggests that disturbances in gut microbiota might participate in the secondary injury through the accumulation of partial metabolites that activate oxidative stress and inflammatory responses. Findings from this study provide a new theoretical basis for improving the secondary injury after spinal cord injury through fecal microbial transplantation.

Synthesis and Characterization of Novel Copolymers Based on 3(S)-Methyl-Morpholine-2,5-Dione

A series of novel copolymers were successfully synthesized by ring-opening polymerization （ROP） of 3 （S）-methyl-morpholine-2,5-dione （MMD） and 5-methyl-5-benzyloxycarbonyl-1,3-dioxan-2-one （MBC） using stan- nous octoate as catalyst. The copolymers were characterized by means of ~H-NMR and FT-IR spectroscopy. Gel permeation chromatography （GPC） test shows that the average-number relative molecular mass and average-weight rela- tive molecular mass slightly increase with the increase of MBC content in feed. The results of differential scanning calorimetry （DSC） demonstrate that the glass transition temperature of copolymers increases with the increase of MBC content in copolymers. The copolymers of MMD and MBC are amorphous copolymers, as indicated by DSC results, while the homopolymer of MMD is semicrystalline.