Parkinson's disease (PD) is a progressively debilitating neurodegenerative condition that leads to motor and cognitive dysfunction. At present, clinical treatment can only improve symptoms, but cannot effectively protect dopaminergic neurons. Several reports have demonstrated that human umbilical cord mesenchymal stem cells (hucMSCs) afford neuroprotection, while their application is limited because of their uncontrollable differentiation and other reasons. Stem cells communicate with cells through secreted exosomes (Exos), the present study aimed to explore whether Exos secreted by hucMSCs could function instead of hucMSCs. hucMSCs were successfully isolated and characterized, and shown to contribute to 6-hydroxydopamine (6-OHDA)-stimulated SH-SY5Y cell proliferation; hucMSC-derived Exos were also involved in this process. The Exos were purified and identified, and then labeled with PKH 26, it was found that the Exos could be efficiently taken up by SH-SY5Y cells after 12 h of incubation. Pretreatment with Exos promoted 6-OHDA-stimulated SH-SY5Y cells to proliferate and inhibited apoptosis by inducing autophagy. Furthermore, Exos reached the substantia nigra through the blood-brain barrier (BBB) in vivo, relieved apomorphine-induced asymmetric rotation, reduced substantia nigra dopaminergic neuron loss and apoptosis, and upregulated the level of dopamine in the striatum. These results demonstrate that hucMSCs-Exos have a treatment capability for PD and can traverse the BBB, indicating their potential for the effective treatment of PD.
Finite element numerical simulations were carried out in 2D geometries to map the magnetic field and force distribution produced by rectangular permanent magnets as a function of their size and position with respect to a microchannel. A single magnet, two magnets placed in attraction and in repulsion have been considered. The goal of this work is to show where magnetic beads are preferentially captured in a microchannel. These simulations were qualitatively corroborated, in one geometrical case, by microscopic visualizations of magnetic bead plug formation in a capillary. The results show that the number of plugs is configuration dependent with: in attraction, one plug in the middle of the magnets; in repulsion, two plugs near the edges of the magnets; and with a single magnet, a plug close to the center of the magnet. The geometry of the magnets (h and l are the height and length of the magnets respectively) and their relative spacing s has a significant impact on the magnetic flux density. Its value inside a magnet increases with the h/l ratio. Consequently, bar magnets produce larger and more uniform values than flat magnets. The l/s ratio also influences the magnetic force value in the microchannel, both increasing concomitantly for all the configurations. In addition, a zero force zone in the middle appears in the attraction configuration as the l/s ratio increases, while with a single magnet, the number of maxima and minima goes from one to two, producing two focusing zones instead of only one.
Protein A-coated magnetic beads (0.3 mm) have been trapped in a small portion of a neutrally coated capillary (50 mm id). Anti-b-lactoglobulin (b-LG) antibodies have then been immobilized on the beads through strong affinity with protein A to subsequently capture b-LG from model or real samples. Once the immunocomplexes formed at physiological pH, a discontinuous buffer system has been used to release the partners and preconcentrate them by transient ITP. The antigens and antibodies have finally been separated by CZE and detected by UV absorbance. An LOQ of 55 nM has been achieved. This methodology has been applied to quantify native b-LG in pasteurized and ultra-high-temperature-treated bovine milk. All the described procedures, including immunosorbent preparation, sample extraction, cleanup, preconcentration, and separation are completely automated on a commercial CE instrument. As this CE immunoassay method is simple, rapid, selective, and sensitive, it should be a practical and attractive technology for the analysis of complicated biological samples.
A magnetic beads based immunoaffinity capillary electrophoresis method for total Immunoglobulin E quantification in serum has been developed. The method combines speed, automation ability, and minimal sample consumption. Only 1 µL of serum is required while the whole immunoaffinity capillary electrophoresis method is performed in less than 50 min. The concomitant use of online immunocapture, transient isotachophoresis, and laserinduced fluorescence detection provides a sensitivity in the low picomolar range and a highly linear fluorescence response over 4 orders of magnitude (IgE concentration ranging from 2.4 to 2400 ng/mL). After validation with a reference material, the method has been successfully applied to the quantification of total IgEs in patient sera. The results compared well with classical ImmunoCap data.
Garnet-bearing mafic granulite and amphibolite exposed as lenses, boudins, or interlayers within metasediments in the Qingshigou area, Dunhuang block, southernmost Central Asian orogenic belt, record important information for understanding the tectono-metamorphic evolution of subduction and collision zones in the southern Central Asian orogenic belt during the mid-Paleozoic. Three stages of metamorphic assemblages (M1, M2, M3) are recognized in the high-and medium-pressure mafic granulite and amphibolite. In the high-pressure mafic granulite, the prograde assemblage (M1) is represented by inclusion minerals (hornblende + plagioclase + quartz) preserved in garnet porphyroblasts; the metamorphic peak assemblage (M2) is characterized by garnet porphyroblasts and matrix minerals (garnet + clinopyroxene + plagioclase + quartz ± zircon ± titanite); and the retrograde assemblage (M3) is marked by coronitic symplectite (hornblende + plagioclase + quartz ± magnetite) rimming the garnet porphyroblasts. In the medium-pressure mafic granulite, the prograde assemblage (M1) of hornblende + plagioclase + quartz is included in the garnet porphyroblasts; the peak assemblage (M2) consists of garnet + orthopyroxene + clinopyroxene + plagioclase + quartz ± zircon ± titanite (M2) in the matrix; and the retrograde assemblage (M3) of hornblende + orthopyroxene + plagioclase + quartz (M3) surrounds the garnet porphyroblasts. In the amphibolite, the prograde assemblage (hornblende + plagioclase + quartz + ilmenite) is preserved as inclusions in garnet (M1); the peak assemblage (M2) is composed of garnet + hornblende + plagioclase + quartz ± zircon ± titanite; and the retrograde assemblage (M3), consisting of hornblende + biotite + plagioclase + quartz + epidote + magnetite, rings the garnet porphyroblasts. Geothermobarometric calculations suggest that the metamorphic pressure-temperature paths pass from 568 °C and 8.8 kbar through 607 °C and 10.6 kbar and 861 °C and 16.9 kbar and finally to 598 °C and 4.4 kbar for the high-pressure mafic granulite; from 756 °C and 9.0 kbar through 750-874 °C and 9.3-11.6 kbar to 675 °C and 4.7 kbar for the medium-pressure mafic granulite; and from 686 °C and 7.6 kbar through 715-766 °C and 10.6-11.2 kbar to 671 °C and 5.6 kbar for the amphibolite, and the paths show clockwise pressuretemperature loops typical of an orogenic process. The metamorphic peak of the high-pressure mafic granulite lies in the eclogite facies, which is indicative of a subduction zone environment. High-resolution secondary ion mass spectrometry (SIMS) U-Pb dating of metamorphic zircon indicates that the metamorphism occurred in the Early Silurian (ca. 430 Ma) and lasted for at least 65 m.y. This study reveals a possible southward subduction history of a branch of the Paleo-Asian Ocean, the Liuyuan Ocean, from the Silurian to Late Devonian, which may be an important event in the accretionary history of the Central Asian orogenic belt.
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