Incorporation of Lysine-Containing Copolymer with Polyurethane Affording Biomaterial with Specific Adsorption of Plasminogen

A novel biomaterial based on polyurethane (PU) was prepared through physical incorporation of lysine-containing copolymer to improve its hemocompatibility and surface recognition of plasminogen.The lysine-containing copolymer was synthesized via the copolymerization of 2-ethylhexyl methacrylate (EHMA),oligo (ethylene glycol)methyl ether methacrylate (OEGMA) and 6-tert-butoxycarbonyl amino-2-(2-methyl-acryloylamino)-hexanoic acid tert-butyl ester (Lys(P)MA),followed by the deprotection of COOH and ε-NH2 groups on lysine residues in the copolymer.The composition of the copolymer can be adjusted by varying the monomer feed ratio.The three components contribute to improving the compatibility with PU,resistance to nonspecific protein adsorption and specific binding of plasminogen,respectively.The binding capacity towards plasminogen increased with the lysine content in the copolymer.This approach illustrates a simple way for the generation of novel biomaterials with improved hemocompatibility and surface recognition of specific biomolecules.     

Efficient Chemical Protein Synthesis using Fmoc-Masked N-Terminal Cysteine in Peptide Thioester Segments

We report an operationally simple method to facilitate chemical protein synthesis by fully convergent and one-pot native chemical ligations utilizing the fluorenylmethyloxycarbonyl (Fmoc) moiety as an N-masking group of the N-terminal cysteine of the middle peptide thioester segment(s). The Fmoc group is stable to the harsh oxidative conditions frequently used to generate peptide thioesters from peptide hydrazide or o-aminoanilide. The ready availability of Fmoc-Cys(Trt)-OH, which is routinely used in Fmoc solid-phase peptide synthesis, where the Fmoc group is pre-installed on cysteine residue, minimizes additional steps required for the temporary protection of the N-terminal cysteinyl peptides. The Fmoc group is readily removed after ligation by short exposure (<7 min) to 20 % piperidine at pH 11 in aqueous conditions at room temperature. Subsequent native chemical ligation reactions can be performed in presence of piperidine in the same solution at pH 7.     

Single-Step Hydrothermal Synthesis of Biochar from H3PO4-Activated Lettuce Waste for Efficient Adsorption of Cd(II) in Aqueous Solution

Developing an ideal and cheap adsorbent for adsorbing heavy metals from aqueous solution has been urgently need. In this study, a novel, effective and low-cost method was developed to prepare the biochar from lettuce waste with H₃PO₄ as an acidic activation agent at a low-temperature (circa 200 °C) hydrothermal carbonization process. A batch adsorption experiment demonstrated that the biochar reaches the adsorption equilibrium within 30 min, and the optimal adsorption capacity of Cd(II) is 195.8 mg∙g⁻¹ at solution pH 6.0, which is significantly improved from circa 20.5 mg∙g⁻¹ of the original biochar without activator. The fitting results of the prepared biochar adsorption data conform to the pseudo-second-order kinetic model (PSO) and the Sips isotherm model, and the Cd(II) adsorption is a spontaneous and exothermic process. The hypothetical adsorption mechanism is mainly composed of ion exchange, electrostatic attraction, and surface complexation. This work offers a novel and low-temperature strategy to produce cheap and promising carbon-based adsorbents from organic vegetation wastes for removing heavy metals in aquatic environment efficiently.     

反相高效液相色谱/电喷雾质谱法测定血浆中盐酸舍曲林

采用反相高效液相色谱-电喷雾质谱法(LC-ESI/MS)测定人体血浆中盐酸舍曲林。以盐酸丙咪嗪为内标,按内标法定量。血浆样品经pH 10.00碳酸钠溶液碱化,加入甲基叔丁基醚萃取,离心分离,取上清液吹干,用流动相溶解进样。色谱柱:RP-Extend-C18(150 mm×4.6 mm,5μm),柱温:40℃;流动相:pH 3.00的三氟乙酸溶液-甲醇(40∶60,V/V),流速0.6 mL/m in。质谱采用选择离子监控模式,检测离子的核质比(m/z)分别是281(丙咪嗪)和159(舍曲林)。舍曲林和丙咪嗪的保留时间分别是5.4 m in和3.8 m in;舍曲林标准曲线线性范围为1~80μg/L;检出限为1.0μg/L(S/N>10);日间、日内相对标准差均小于6.0%,相对回收率为90%~106%;提取回收率在75%~93%范围内。此法适合人体药代动力学的血浆样品的分析,结果准确、可靠。     

Design and Activity of Novel Oxadiazole Based Compounds That Target Poly(ADP-ribose) Polymerase

Novel PARP inhibitors with selective mode-of-action have been approved for clinical use. Herein, oxadiazole based ligands that are predicted to target PARP-1 have been synthesized and screened for the loss of cell viability in mammary carcinoma cells, wherein seven compounds were observed to possess significant IC₅₀ values in the range of 1.4 to 25 µM. Furthermore, compound 5u, inhibited the viability of MCF-7 cells with an IC₅₀ value of 1.4µM, when compared to Olaparib (IC₅₀ = 3.2 µM). Compound 5s also decreased cell viability in MCF-7 and MDA-MB-231 cells with IC₅₀ values of 15.3 and 19.2 µM, respectively. Treatment of MCF-7 cells with compounds 5u and 5s produced PARP cleavage, H2AX phosphorylation and CASPASE-3 activation comparable to that observed with Olaparib. Compounds 5u and 5s also decreased foci-formation and 3D Matrigel growth of MCF-7 cells equivalent to or greater than that observed with Olaparib. Finally, in silico analysis demonstrated binding of compound 5s towardsthe catalytic site of PARP-1, indicating that these novel oxadiazoles synthesized herein may serve as exemplars for the development of new therapeutics in cancer.     

Unravelling the Helianthus tuberosus L. (Jerusalem Artichoke,Kiku-Imo) Tuber Proteome by Label-Free Quantitative Proteomics

The present research investigates the tuber proteome of the ‘medicinal’ plant Jerusalem artichoke (abbreviated as JA) (Helianthus tuberosus L.) using a high-throughput proteomics technique. Although JA has been historically known to the Native Americans, it was introduced to Europe in the late 19th century and later spread to Japan (referred to as ‘kiku-imo’) as a folk remedy for diabetes. Genboku Takahashi research group has been working on the cultivation and utilization of kiku-imo tuber as a traditional/alternative medicine in daily life and researched on the lowering of blood sugar level, HbA1c, etc., in human subjects (unpublished data). Understanding the protein components of the tuber may shed light on its healing properties, especially related to diabetes. Using three commercially processed JA tuber products (dried powder and dried chips) we performed total protein extraction on the powdered samples using a label-free quantitate proteomic approach (mass spectrometry) and catalogued for the first time a comprehensive protein list for the JA tuber. A total of 2967 protein groups were identified, statistically analyzed, and further categorized into different protein classes using bioinformatics techniques. We discussed the association of these proteins to health and disease regulatory metabolism. Data are available via ProteomeXchange with identifier PXD030744.     

Are Words the Quanta of Human Language? Extending the Domain of Quantum Cognition

In previous research, we showed that ‘texts that tell a story’ exhibit a statistical structure that is not Maxwell–Boltzmann but Bose–Einstein. Our explanation is that this is due to the presence of ‘indistinguishability’ in human language as a result of the same words in different parts of the story being indistinguishable from one another, in much the same way that ’indistinguishability’ occurs in quantum mechanics, also there leading to the presence of Bose–Einstein rather than Maxwell–Boltzmann as a statistical structure. In the current article, we set out to provide an explanation for this Bose–Einstein statistics in human language. We show that it is the presence of ‘meaning’ in ‘texts that tell a story’ that gives rise to the lack of independence characteristic of Bose–Einstein, and provides conclusive evidence that ‘words can be considered the quanta of human language’, structurally similar to how ‘photons are the quanta of electromagnetic radiation’. Using several studies on entanglement from our Brussels research group, we also show, by introducing the von Neumann entropy for human language, that it is also the presence of ‘meaning’ in texts that makes the entropy of a total text smaller relative to the entropy of the words composing it. We explain how the new insights in this article fit in with the research domain called ‘quantum cognition’, where quantum probability models and quantum vector spaces are used in human cognition, and are also relevant to the use of quantum structures in information retrieval and natural language processing, and how they introduce ‘quantization’ and ‘Bose–Einstein statistics’ as relevant quantum effects there. Inspired by the conceptuality interpretation of quantum mechanics, and relying on the new insights, we put forward hypotheses about the nature of physical reality. In doing so, we note how this new type of decrease in entropy, and its explanation, may be important for the development of quantum thermodynamics. We likewise note how it can also give rise to an original explanatory picture of the nature of physical reality on the surface of planet Earth, in which human culture emerges as a reinforcing continuation of life.     

An In Vitro Anticancer,Antioxidant, and Phytochemical Study on Water Extract of Kalanchoe daigremontiana Raym.-Hamet and H. Perrier

Kalanchoe species are succulents with anti-inflammatory, antioxidant, and analgesic properties, as well as cytotoxic activity. One of the most popular species cultivated in Europe is Kalanchoe daigremontiana Raym.-Hamet and H. Perrier. In our study, we analyzed the phytochemical composition of K. daigremontiana water extract using UHPLC-QTOF-MS and estimated the cytotoxic activity of the extract on human ovarian cancer SKOV-3 cells by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, flow cytometry, luminometric, and fluorescent microscopy techniques. The expression levels of 92 genes associated with cell death were estimated via real-time PCR. The antioxidant activity was assessed via flow cytometry on human keratinocyte HaCaT cell line. The DPPH (2,2-diphenyl-1-picrylhydrazyl) radical and FRAP (ferric-reducing antioxidant power) assays were also applied. We identified twenty bufadienolide compounds in the water extract and quantified eleven. Bersaldegenin-1,3,5-orthoacetate and bryophyllin A were present in the highest amounts (757.4 ± 18.7 and 573.5 ± 27.2 ng/mg dry weight, respectively). The extract showed significant antiproliferative and cytotoxic activity, induced depolarization of the mitochondrial membrane, and significantly arrested cell cycle in the S and G2/M phases of SKOV-3 cells. Caspases-3, 7, 8, and 9 were not activated during the treatment, which indicated non-apoptotic cell death triggered by the extract. Additionally, the extract increased the level of oxidative stress in the cancer cell line. In keratinocytes treated with menadione, the extract moderately reduced the level of oxidative stress. This antioxidant activity was confirmed by the DPPH and FRAP assays, where the obtained IC₅₀ values were 1750 ± 140 and 1271.82 ± 53.25 μg/mL, respectively. The real-time PCR analysis revealed that the extract may induce cell death via TNF receptor (tumor necrosis factor receptor) superfamily members 6 and 10.