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Extended lipid anchorage and peripheral binding appear to prevail at low and high CL/ycc molar ratios, respectively. Simultaneous deletion of two or three surface positive charges from Site A does not abolish CL binding, but instead increases protein affinity for CL. MD calculations suggest this unexpected behavior results from the mutation-induced severe weakening of the H-bond connecting the Nε of His26 with the backbone oxygen of Glu44, which lowers the conformational stability compared to the wt species, overcoming the decreased surface electrostatic interaction.Nanoformulations, prodrugs, and targeted therapies are among the most intensively investigated approaches to new cancer therapeutics. Human ferritin has been used extensively as a nanocarrier for the delivery of drugs and imaging agents to cancerous tumor cells both in vitro and in vivo. We report exploitation of the native properties of ferritin, which can be co-loaded with simple forms of iron (FeOOH) and arsenic (arsenate) in place of the native phosphate. The As(III) form arsenic trioxide has been successfully used to treat one blood cancer, but has so far proven too systemically toxic for use on solid tumors in the clinic. The As(V) form, arsenate, on the other hand, while much less systemically toxic upon bolus injection has also proven ineffective for cancer therapy. We extended the C-terminal ends of the human ferritin subunits with a tumor cell receptor targeting peptide and loaded this modified ferritin with ~ 800 arsenates and ~ 1100 irons. Our results demonstrate targeting and uptake of the iron, arsenate-loaded modified human ferritin by breast cancer cells. At the same arsenic levels, the cytotoxicity of the iron, arsenate-loaded human ferritin was equivalent to that of free arsenic trioxide and much greater than that of free arsenate. The iron-only loaded human ferritin was not cytotoxic at the highest achievable doses. The results are consistent with the receptor-targeted human ferritin delivering arsenate as a reductively activated 'prodrug'. This targeted delivery could be readily adapted to treat other types of solid tumor cancers.PURPOSE A retrospective analysis was carried out to compare the results of patch repair using ready-made, synthetic mesh (PR) and sutured repair (SR) based on standard protocols. The accumulated recurrence rate was accepted as the primary outcome. Pain at rest and during exercise, cosmetic effect and treatment satisfaction were chosen as the secondary endpoints. METHODS Adult patients after elective, open surgical repair of a single, primary umbilical hernia less then 2 cm in diameter were included. Patients with incarceration or strangulation, after previous umbilical hernia repair or other abdominal surgical interventions were excluded. In the SR group, single-layer sutures were placed using the short-stitch technique. In PR group, a 6.3-mm ready-made Parietene Ventral Patch (Medtronic) was used. RESULTS 161 patients (104 in PR and 57 in SR groups) were included in the study (22 months follow-up). Nine recurrences were observed [six in PR (5.8%) and three in SR group (5.2%)]. In PR group, three patients (2.9%) reported complaints at rest and none in SR group, while 18 patients (17.3%) in PR group reported pain during exercises and 7 (12.3%) in SR group. CONCLUSION For the smallest umbilical hernias, the use of dense fascia suturing (short-stitch technique) may be an effective alternative to patch repair techniques in patients with no additional risk factors for recurrence. The mesh patch repair method is associated with a significantly higher risk of postsurgical pain. Diastasis recti is a factor favoring umbilical hernia recurrence after both pure tissue repair and patch repair.The poly[(9,9-dioctylfuorenyl-2,7-diyl)-alt-co-(1,4-benzo-2,1',3-thiadiazole)] (PFBT) was carboxyl-functionalized to prepare polymer dots (C-PFBT Pdots), which served as a self-ECL emitter for producing an extraordinary ECL signal without any exogenous coreactants. The C-PFBT Pdots-modified electrode captured the substrate DNA and further hybridized with a ferrocene (Fc)-labeled DNA. The ECL emission of C-PFBT Pdots was quenched by Fc (a signal off state). After the DNAzyme was added, the DNAzyme-substrate hybrids were formed through hybridizing between DNAzyme and substrate and the Fc-labeled DNA was released. see more In the presence of target Pb2+, the DNAzyme-substrate hybrids could be specifically recognized and cleaved to release the DNAzyme and Pb2+. Ultimately, the released DNAzyme would further hybridize with the substrate for producing the DNAzyme-substrate hybrids and then were cleaved by the released Pb2+. As a result, the DNA walking machine was generated and the substantial Fc was away from C-PFBT Pdots to obtain a signal on state. Such a strategy achieved a sensitive detection of Pb2+ and the detection limit was as low as 0.17 pM. Moreover, making this ECL biosensor for an intracellular Pb2+ detecting, a convincing performance was achieved. The self-ECL emitter C-PFBT Pdots combining with the quencher Fc provided a new strategy and platform for constructing a coreactant-free ECL assay.In order to overcome the antibody-based sensor's shortcomings, an electrochemical aptamer (Apt)-based sensor was developed for amyloid-β40 oligomer (Aβ40-O). The aptasensor was constructed by locating Apt and ferrocence (Fc) on streptavidin-modified gold (SA-gold) nanoparticles. The obtained AptFc@SA-gold nanoparticles were linked onto the Au electrode via the connection of double-stranded DNA (dsDNA) as a "conductive spring." The determination of Aβ40-O was performed with square-wave voltammetry (SWV). Upon bio-recognition between Apt and Aβ40-O, the conformation of Apt changed and the formed Apt/Aβ40-O complex separated from the SA-gold surface. As a result, the surface charge of SA-gold positively shifted, weakening the electrostatic attraction between the SA-gold and the positively charged Au electrode surface (at potential range of 0.1~0.5 V, corresponding to the Fc redox transformation), and stretching the dsDNA chain. Based on the exponential decay of dsDNA's electron transfer efficiency on its chain stretching, the oxidation current density from Fc decreased and displayed linear correlation to the concentration of Aβ40-O.
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