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The complications of hemodialysis accompanied the hemodialysis and threaten the patients life. Besides the loss of nutrient substance, such as amino acid and vitamin, we found new clues that the adsorbed proteins on common-used polysulfone-based dialysis membrane might be the reason according to the qualitative proteomic study by ionic liquid assisted sample preparation method. Our results indicated that the adsorbed proteins on the membrane were related with complement activation, blood coagulation, and leukocyte-related biological process. The quantitative proteome further demonstrated some significant changes of signal proteins in the post-dialysis plasma after the hemodialysis, such as beta-2-microglobulin and platelet factor-4, which would further verify these new clues.

We recently reported the identification and characterization of a novel small chemical molecule designated FL118. FL118 selectively inhibits multiple cancer survival and proliferation-associated antiapoptotic proteins (survivin, Mcl-1, XIAP, cIAP2) and eliminates small and large human tumor xenografts in animal models (Ling et al., PLoS One 2012, 7, e45571). Here, we report a follow-up study on the structure-activity relationship (SAR) of the hydroxyl group in the lactone ring of FL118. We found that the superior antitumor efficacy of FL118 heavily depends on its steric configuration through comparing the antitumor activity of FL118 with FL113 (the racemic mixture of FL118). Consistently, FL118 proved much more effective in inhibiting the expression of survivin, Mcl-1, and cIAP2, both in vitro and in vivo, compared to FL113. Additionally, Tet-on controlled induction of survivin or forced expression of Mcl-1 protects cancer cells from FL118-mediated growth inhibition and cell death. To further explore the SAR, we synthesized seven position 20-esterifiable FL118 and FL113 derivatives. Studies on these seven new compounds revealed that keeping a free hydroxyl group of FL118 is also important for high antitumor efficacy. Together, these studies confirm the superior anticancer activity of FL118 and narrow the window for further SAR studies to generate novel analogues based on FL118 core structure on its other potential chemical positions.

A series of novel potential DNA bis-intercalators were designed and synthesized, in which two glucuronic acids were linked by ethylenediamine, and the glucuronic acid was coupled with various chromophores, including quinoline, acridine, indole and purine, at the C-1 position. The preliminary binding properties of these compounds to calf thymus DNA (CT-DNA) have been investigated by UV-absorption and fluorescence spectroscopy. The results indicated that all the target compounds can interact with CT-DNA, and the acridine derivative, 3b, showed the highest key selection vector (KSV) value, which suggested that compound 3b binds most strongly to CT-DNA.

High-performance unipolar n-type polymer semiconductors are critical for advancing the field of organic electronics, which relies on the design and synthesis of new electron-deficient building blocks with good solubilizing capability, favorable geometry, and optimized electrical properties. Herein, two novel imide-functionalized thiazoles, 5,5'-bithiazole-4,4'-dicarboxyimide (BTzI) and 2,2'-bithiazolothienyl-4,4',10,10'-tetracarboxydiimide (DTzTI), are successfully synthesized. Single crystal analysis and physicochemical study reveal that DTzTI is an excellent building block for constructing all-acceptor homopolymers, and the resulting polymer poly(2,2'-bithiazolothienyl-4,4',10,10'-tetracarboxydiimide) (PDTzTI) exhibits unipolar n-type transport with a remarkable electron mobility (μe ) of 1.61 cm2 V-1 s-1 , low off-currents (Ioff ) of 10-10 -10-11 A, and substantial current on/off ratios (Ion /Ioff ) of 107 -108 in organic thin-film transistors. The all-acceptor homopolymer shows distinctive advantages over prevailing n-type donor-acceptor copolymers, which suffer from ambipolar transport with high Ioff s > 10-8 A and small Ion /Ioff s < 105 . The results demonstrate that the all-acceptor approach is superior to the donor-acceptor one, which results in unipolar electron transport with more ideal transistor performance characteristics.

Tissue kallikrein, generally existing in living bodies as prokallikrein, is a serine proteinase that has proven of great significance to treat hypertension, cardiopathy and nephropathy. Although the extraction of tissue kallikrein from human urine is the most commonly used method to obtain such a protein, not only the yield is very little, but also the procedure is rather complex. Furthermore, the biological safety is uncertain. Therefore, the preparation of such a protein by genetic engineering method, including gene expression, cell culture, separation and purification, is very important. In this paper, a new method to obtain purified tissue prokallikrein excreted from insect cells by liquid chromatography has been proposed. In contrast to the previously published papers, the purification procedure is simplified to only three steps with the final yield of 57% and the purity of 95%, which is not only convenient, but also low-cost and suitable for the large-scale preparation of such a protein. The purified protein is further validated as prokallikrein by high performance liquid chromatography-mass spectrometry and amino acid sequencing.

Hemodialysis is one of the most important therapies for patients with uremia, and the dialysis membrane is the predominant factor that impacts the efficiency of dialysis. Here, a protein adsorption on two different membranes is investigated to provide a basis for improving dialysis materials. Two cases treated with the Polyflux 14L low-flux dialyzer and the Polyflux 140H high-flux dialyzers during two continuous therapies are selected. Four used dialyzers from selected patients are infused with C12Im-Cl to elute the adsorbed proteins. Then labeled digested proteins adsorb by Polyflux 140H and Polyflux 14L with 13 CD2 O and NaCNBD3 (light labeling, L) and CD2 O and NaCNBH3 (heavy labeling, H), respectively. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used to identify the proteins. According to the ratio (Light labeling/Heavy labeling), the eluted proteins are divided into three groups: significantly higher, significantly lower, and no significant differences with a ratio of >2, 2), 320 proteins are retained more by the Polyflux 14L membrane (ratio

Tangential flow affinity membrane cartridge (TFAMC) fs a new model of immunoadsorption therapy for hemoperfusion. Recombinant Protein A was immobilized on the membrane cartridge through Schiff base formation for extracorporeal IgG and immune complex removal from blood. Flow characteristics, immunoadsorption capacity and biocompatibility of protein A TFAMC were studied. The results showed that the pressure drop increased with the increasing flow rate of water, plasma and blood, demonstrating reliable strength of membrane at high now rare. The adsorption capacities of protein A TFAMC for IgG from human plasma and blood were measured. The cartridge with 139 mg protein A immobilized on the matrix (6 mg protein A/g dry matrix) adsorbed 553 mg IgG (23.8 mg IgG/g dry matrix) from human plasma and 499.4 mg IgG (21.5 mg IgG/g dry matrix) from human blood, respectively. The circulation time had a major influence on IgG adsorption capacity, but the flow rate had little influence. Experiments in vitro and in vivo confirmed that protein A TFAMC mainly adsorbed Ige and Little of other plasma proteins, and that blood cell damage was negligible. The extracorporeal circulation system is safe and reliable. Copyright (C) 1999 John Wiley & Sons, Ltd.