Radiosynthesis and evaluation of 188Re-c(RGDyK)-His as a novel radiotherapeutic agent for integrin αvβ3 targeting tumour

The successes of noninvasive methods to visualize and quantify integrin α_vβ₃ expression in vivo have paved the way for radiolabeling anti-integrin therapy in clinic. Arginine-glycine-aspartice (RGD) peptide and related derivatives labeled with radionuclides for radio-therapy, which specifically targeting integrin α_vβ₃-positive tumors, could be used to treat these tumors. We have labeled c(RGDyK)-His, a RGD derivative, with ¹⁸⁸Re and the radio-therapy efficiency has been evaluated in model nude mice. c(RGDyK)-His was labeled with ¹⁸⁸Re by chelating with [¹⁸⁸Re(CO)₃(H₂O)₃]⁺ under a slightly basic condition. The in vitro specific binding affinity to U87 MG cell lines and the biodistribution of ¹⁸⁸Re-c(RGDyK)-His in the animal tumor models was measured. The inhibitory effects of ¹⁸⁸Re-c(RGDyK)-His were observed more than 1 month, and evaluated by microPET/CT imaging with ¹⁸F-FDG. Results of in vivo, cell uptake demonstrated ¹⁸⁸Re-c(RGDyK)-His had a high specific binding affinity to receptor integrin α_vβ₃. In biodistribution experiment, ¹⁸⁸Re-c(RGDyK)-His was accumulated in the tumor and cleared fast from the normal tissues. In radiotherapy study, tumor growth inhibition was significantly higher in the treatment groups than in the control groups. These studies showed that ¹⁸⁸Re-c(RGDyK)-His could be effectively used for integrin α_vβ₃ targeting therapy. This may offer a potential therapeutic strategy for the treatment of integrin-positive tumors in clinic.     

新型吡唑联吡咯类杂环化合物的合成及杀菌活性

为寻找具有更高生物活性、更环保的新农药杀菌剂,基于杀菌剂氟咯菌腈设计并合成了10个新型吡唑联吡咯类杂环化合物,以吡唑环代替氟咯菌腈上原有的苯环,以期提高其杀菌活性.采用1H NMR,FTIR,单晶X射线衍射、元素分析和熔点测定等测试手段对目标化合物及其中间体的结构进行了表征与确认,并通过挥发法培养得到了6个目标化合物的单晶.还对其中6个化合物进行了生物活性测试,测试结果表明各化合物对水稻纹枯病、黄瓜灰霉病、黄瓜霜霉病均表现出一定的抑菌效果,可作为先导化合物对其结构进行深入的研究,为新农药杀菌剂的开发提供了理论支持.     

Sensitive detection of T4 polynucleotide kinase activity based on coupled exonuclease reaction and nicking enzyme-assisted fluorescence signal amplification

As a prominent member of the 5′-kinase family, T4 polynucleotide kinase (PNK) plays an important role in gene function regulations, and the study of PNK activity and its potential inhibitors is significant for research related to the DNA phosphorylation process. Here, we proposed a novel strategy for the detection of PNK activity and its inhibition, which combines exonuclease enzyme reaction and nicking enzyme-assisted fluorescence signal amplification. Through recycling cleavage of DNA fluorescence probe for signal amplification, a highly sensitive PNK sensing platform is developed, and a very low detection limit of 0.05 mU/mL is achieved, which is better than or comparable to that of the previously reported PNK assays. The present approach adopts a simple separation-free procedure in which the enzyme assay is conducted in homogeneous solutions. Additionally, the inhibitory effects of several known kinase inhibitors on PNK have been successfully detected. Since the proposed assay exhibits the advantages of high sensitivity and simplicity, it holds great potential in providing a promising platform for convenient and highly sensitive detection of PNK activity and its inhibitors.

Ethanol synthesis from syngas on Mn- and Fe-promoted Rh/γ-Al2O3

The catalytic hydrogenation of CO was studied over Mn- and/or Fe-promoted Rh/γ-Al₂O₃ catalysts. The catalysts were characterized by means of XRD, BET, H₂-TPR·H₂-TPD, XPS and DRIFTS. CO hydrogenation results showed that the doubly Mn- and Fe-promoted Rh/γ-Al₂O₃ catalysts exhibited superior catalytic activity and better ethanol selectivity. The DRIFTS results showed that Mn promoter stabilized the adsorbed CO on Rh⁺ and Fe stabilized adsorbed CO on Rh⁺ and Rh⁰, especially Rh⁰. The fact that doubly Mn- and Fe-promoted Rh/γ-Al₂O₃ owned more (Rhx⁰–Rhy⁺)–O–Fe³⁺·(Fe²⁺) active species was proposed to be a crucial factor accounting for its higher ethanol selectivity.     

Quantitative characterization by asymmetrical flow field-flow fractionation of IgG thermal aggregation with and without polymer protective agents

Complexes formed between poly(acrylates) and polyclonal immunoglobulin G (IgG) in its native conformation and after heat stress were characterized using asymmetric flow field-flow fractionation (AF4) coupled with on-line UV-Vis spectroscopy and multi-angle light-scattering detection (MALS). Mixtures of IgG and poly(acrylates) of increasing structural complexity, sodium poly(acrylate) (PAA), a sodium poly(acrylate) bearing at random 3 mol % n-octadecyl groups, and a random copolymer of sodium acrylate (35 mol %), N-n-octylacrylamide (25 mol %) and N-isopropylacrylamide (40 mol %), were fractionated in a sodium phosphate buffer (0.02 M, pH 6.8) in the presence, or not, of 0.1 M NaCl. The AF4 protocol developed allowed the fractionation of solutions containing free poly(acrylates), native IgG monomer and dimer, poly(acrylates)/IgG complexes made up of one IgG molecule and a few polymer chains, and/or larger poly(acrylates)/IgG aggregates. The molar mass and recovery of the soluble analytes were obtained for mixed solutions of poly(acrylates) and native IgG and for the same solutions incubated at 65 °C for 10 min. From the combined AF4 results, we concluded that in solutions of low ionic strength, the presence of PAA increased the recovery ratio of IgG after thermal stress because of the formation of electrostatically-driven PAA/IgG complexes, but PAA had no protective effect in the presence of 0.1 M NaCl. Poly(acrylates) bearing hydrophobic groups significantly increased IgG recovery after stress, independently of NaCl concentration, because of the synergistic effect of hydrophobic and electrostatic interactions. The AF4 results corroborate conclusions drawn from a previous study combining four analytical techniques. This study demonstrates that AF4 is an efficient tool for the analysis of protein formulations subjected to stress, an important achievement given the anticipated important role of proteins in near-future human therapies. ?      

氮掺杂氧化石墨催化苄胺氧化

酰胺类化合物是重要的化工原料和生物医药合成的中间体,但其制备大部分需要使用贵金属催化剂,因此,发展廉价金属乃至非金属催化剂具有重大意义.本文使用化学气相沉积法合成了氮掺杂的层状氧化石墨材料,并将其应用于苄胺氧化反应中,实现了液相中酰胺合成的非金属催化过程.在水相中可以活化氧气较高产率地生成亚胺化合物N-苄亚甲基苄胺,并且成功实现了在氨水反应介质中高转化率和选择性地生成苯甲酰胺.此外,对反应中的影响因素进行了逐一研究,并从多方面探究了该反应中氨水的作用以及反应最可能的历程,提出了一条经过包括亚胺在内的多个中间产物的反应路径.本工作对于研究碳氢键的活化过程以及拓宽碳催化领域进行了有益的尝试.     

Nitrogen-doped graphene as an excellent candidate for selective gas sensing

The toxic gases,such as CO and NO,are highly dangerous to human health and even cause the death of person and animals in a tiny amount.Therefore,it is very necessary to develop the toxic gas sensors that can instantly monitor these gases.In this work,we have used the first-principles calculations to investigate adsorption of gases on defective graphene nanosheets to seek a suitable material for CO sensing.Result indicates that the vancancy graphene can not selectivly sense CO from air,because O2 in air would disturb the sensing signals of graphene for CO,while the nitrogen-doped graphene is an excellent candidate for selectivly sensing CO from air,because only CO can be chemisorbed on the pyridinic-like N-doped graphene accompanying with a large charge transfer,which can serve as a useful electronic signal for CO sensing.Even in the environment with NO,the N-doped graphene can also detect CO selectively.Therefore,the N-doped graphene is an excellent material for selectively sensing CO,which provides useful information for the design and fabrication of the CO sensors.     

Lipid profiling of mammalian cells with in situ matrix-assisted laser desorption ionization-mass spectrometry

The analysis of cellular lipids and phospholipids has been of continuously increasing research interest due to the importance of these molecules in psychological process. In this work, a mass spectrometry-based method for direct, in situ analysis of lipids in cells was reported. Mammalian cells were directly cultured on ITO-coated glass and then analyzed by matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS). The matrix application process was achieved by electrospray coating, which produced a homogenous layer of matrix crystal on the sample. The detection results and reproducibility are satisfactory. With this method, a profile of abundant membrane lipids is generated, which is characteristic of cell type. In conclusion, this in situ MALDI-MS cellular lipid analysis method provides a platform for sensitive and robust molecular profiling of mammalian cells.     

Thermo-responsive gelatin-functionalized PCL film surfaces for improvement of cell adhesion and intelligent recovery of gene-transfected cells

Efficient local gene transfection on a tissue scaffold is dependent on good cell-adhesion characteristics. In this work, the thermo-responsive gelatin-functionalized polycaprolactone (PCL) films were proposed for improvement of cell adhesion and intelligent recovery of gene-transfected cells. Functional copolymer brushes (PCL-g-P(NIPAAm-co-MAAS)) were first prepared via surface-initiated ATRP of N-isopropylacrylamide (NIPAAm) and methacrylic acid sodium salt (MAAS) from the initiator-funcationalized PCL surfaces. The pendant carboxyl end-groups of the PCL-g-P(NIPAAm-co-MAAS) surface were subsequently coupled with gelatin via carbodiimide chemistry to produce the thermo-responsive gelatin-functionalized PCL surface. The thermo-responsive gelatin-functionalized PCL film surface can improve cell adhesion and proliferation above the LCST of P(NIPAAm) without destroying cell detachment properties at lower temperatures. The dense transfected cells can be recovered simply by lowering culture temperature. The thermo-responsive gelatin-functionalized PCL films are potentially useful as intelligent adhesion modifiers for directing cellular functions within tissue scaffolds.