Plasminogen degrades α-synuclein, Tau and TDP-43 and decreases dopaminergic neurodegeneration in mouse models of Parkinson's disease.

Parkinson's disease (PD) is the second most frequently diagnosed neurodegenerative disease, and it is characterized by the intracellular and extracellular accumulation of α-synuclein (α-syn) and Tau, which are major components of cytosolic protein inclusions called Lewy bodies, in the brain. Currently, there is a lack of effective methods that preventing PD progression. It has been suggested that the plasminogen activation system, which is a major extracellular proteolysis system, is involved in PD pathogenesis. We investigated the functional roles of plasminogen in vitro in an okadaic acid-induced Tau hyperphosphorylation NSC34 cell model, ex vivo using brains from normal controls and methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, and in vivo in a widely used MPTP-induced PD mouse model and an α-syn overexpression mouse model. The in vitro, ex vivo and in vivo results showed that the administered plasminogen crossed the blood‒brain barrier (BBB), entered cells, and migrated to the nucleus, increased plasmin activity intracellularly, bound to α-syn through lysine binding sites, significantly promoted α-syn, Tau and TDP-43 clearance intracellularly and even intranuclearly in the brain, decreased dopaminergic neurodegeneration and increased the tyrosine hydroxylase levels in the substantia nigra and striatum, and improved motor function in PD mouse models. These findings indicate that plasminogen plays a wide range of pivotal protective roles in PD and therefore may be a promising drug candidate for PD treatment.

An efficient binary Gradient-based optimizer for feature selection.

Feature selection (FS) is a classic and challenging optimization task in the field of machine learning and data mining. Gradient-based optimizer (GBO) is a recently developed metaheuristic with population-based characteristics inspired by gradient-based Newton's method that uses two main operators: the gradient search rule (GSR), the local escape operator (LEO) and a set of vectors to explore the search space for solving continuous problems. This article presents a binary GBO (BGBO) algorithm and for feature selecting problems. The eight independent GBO variants are proposed, and eight transfer functions divided into two families of S-shaped and V-shaped are evaluated to map the search space to a discrete space of research. To verify the performance of the proposed binary GBO algorithm, 18 well-known UCI datasets and 10 high-dimensional datasets are tested and compared with other advanced FS methods. The experimental results show that among the proposed binary GBO algorithms has the best comprehensive performance and has better performance than other well known metaheuristic algorithms in terms of the performance measures.

Tibial Nail Combined with Vacuum Sealing Drainage for Gustilo Grade IIIB Open Tibial Fractures: A Patient Series.

Gustilo grade IIIB open tibial fractures are relatively difficult to treat. We investigated the treatment effects of tibial intramedullary nails combined with vacuum sealing drainage (VSD) for Gustilo grade IIIB open tibial fractures. From March 2015 to March 2017, 13 cases of Gustilo grade IIIB open tibial fractures were treated with Expert Tibial Nails combined with VSD. Causes of injury included falls from a height (n = 9, 69.2%) and road accidents (n = 4, 30.8%). The duration from time of injury to hospital intake was 7.3 hours (range 5 to 9.5), and the time between injury and operation was 6.7 days (range 3 to 11). Six months after the operation, overall patient general health was investigated via the American Orthopaedic Foot and Ankle Society (AOFAS) ankle score and the physical and mental health dimensions of the Short-Form Health Survey 36 (SF-36). Postoperative complications and infections also were recorded. The results indicated that the median AOFAS score was 93.7 (range 89 to 97), with all individuals having either excellent (90 to 100; n = 10, 76.9%) or good (80 to 89; n = 3, 23.1%) outcomes. The median physical SF-36 score was 83.1 (range 72.5 to 93.0), and the median mental SF-36 score was 80.6 (range 69.7 to 92.0). Moreover, there were no instances of tibial shortening, neurovascular injury, postoperative complications, implant failure, malunion, or serious infections. In conclusion, intramedullary tibial nail combined with VSD is a safe and effective method to treat type grade IIIB open tibial fractures.

Facile reversible UV-controlled and fast transition from emulsion to gel by using a photoresponsive polymer with a malachite green group.

In this paper we describe the facile reversible UV-controlled and fast transition from emulsion to gel by using a photoresponsive polymer with a malachite green group. The photoresponsive polymer with the hydrophobic malachite green group can be used for the formation of an oil-in-water emulsion. However, upon UV irradiation of 5 min, the photochromic malachite green group could be ionized to its corresponding cation, leading to the transformation from emulsion to gel. Upon shaking, such gel can recover the emulsion state, and further UV irradiation can turn the emulsion into gel again. Such transition from emulsion to gel by photochemical reaction and reverse shaking treatment can be repeated several times. It is anticipated greatly that this line of research may provide new insight into the mechanism behind stimuli-responsive systems, facilitating the design and synthesis of new responsive molecules for the fabrication of stimuli-responsive materials with designed functions.

Fabrication of reactivated biointerface for dual-controlled reversible immobilization of cytochrome C.

A light or pH dual-responsive reactivated biointerface is fabricated using of photocontrolled reversible inclusion and exclusion reactions between photoresponsive azobenzene-containing self-assembled monolayer and pH-responsive poly(acrylic acid) polymer grafted with cyclodextrins. The dual-controlled reactivated biointerface can be employed for reversible immobilization of redox protein-Cytochrome c, triggered by dual external stimuli-light and pH.

Tuning surface wettability through photocontrolled reversible molecular shuttle.

A photocontrolled molecular shuttle SAM based on an alpha-cyclodextrin (alpha-CD)/azobenzene inclusion complex on rough gold surfaces is fabricated, which can reversibly switch the surface wettability by transferring external energy (light) to molecular mechanical motion.

Light-controlled single-walled carbon nanotube dispersions in aqueous solution.

We have succeeded in dispersing single-walled carbon nanotubes (SWNTs) into an aqueous solution of poly(ethylene glycol)-terminated malachite green derivative (PEG-MG) through simple sonication. It was found that UV exposure caused reaggregation of these predispersed SWNTs in the same aqueous medium, as adsorbed PEG-MG photochromic chains could be effectively photocleavaged from the nanotube surface. The observed light-controlled dispersion and reaggragation of SWNTs in the aqueous solution should facilitate the development of SWNT dispersions with a controllable dispersity for potential applications.

Reversible self-organization of a UV-responsive PEG-terminated malachite green derivative: vesicle formation and photoinduced disassembly.

This paper describes the assembly and disassembly of vesicles formed by a UV-responsive poly(ethylene glycol) terminated malachite green derivative. The UV-responsive amphiphile with both a hydrophobic malachite green group and a hydrophilic PEG group can self-organize into vesicles in water before UV irradiation. However, upon UV irradiation, the photochromic moiety can be ionized to its corresponding cation, leading to the disassembly of these vesicles. In addition, the cation can thermally recover its electrically neutral form, and the disassembled species can form vesicles reversibly on the basis of a thermal reverse reaction. The reverse reaction is temperature-controlled and can be speeded up by thermal treatment. By using various characterization techniques, e.g., transmission electron microscopy, dynamic light scattering, UV-visible spectroscopy, and NMR spectroscopy, we have confirmed that the vesicle structures can be formed, disassembled, and recovered by the above-mentioned treatments. It is anticipated greatly that this line of research may provide new insights into the mechanism behind stimuli-responsive formation and rupture of molecular assemblies, facilitating the design and synthesis of new surface active molecules for the fabrication of stimuli-responsive materials with designed functions.

Surface gradient material: from superhydrophobicity to superhydrophilicity.

We have developed a simple method to fabricate a gradient from superhydrophobicity to superhydrophilicity. It is based on the controlled self-assembled monolayer consisting of a thiol molecule on a gold surface and the amplifying effect of the wetting property on a rough surface. Using a relatively dilute HS(CH2)11CH3 solution (0.05 mmol/L), we found that the density of molecules on the surface can be controlled by varying the immersion time. Slowly adding the dilute solution to the container holding the rough gold substrate will lead to a density gradient along the surface. After the complementary adsorption of HS(CH2)10CH2OH, the surface exhibits a gradient from superhydrophobicity to superhydrophilicity. The slope of the gradient can be conveniently tuned by varying the speed of addition. Cassie-Baxter and Wenzel equations are employed to explain this special property based on the rough structure and the molecular composition gradient that have been determined by XPS. This kind of material would provide a larger oriented driving force for many important biological and physical processes and might have potential applications in water droplet movement, oriented axonal specification of neurons, protein adhesion, and so on.

Investigation into pH-responsive self-assembled monolayers of acylated anthranilate-terminated alkanethiol on a gold surface.

This article describes the preparation of pH-responsive self-assembled monolayers (SAMs) of acylated anthranilate-terminated alkanethiol. These monolayers are formed by chemisorption of the alkanethiol molecules onto a gold surface, resulting in different wetting properties of the surfaces depending upon the pH. By using various characterization techniques (e.g., infrared spectroscopy, cyclic voltammetry, contact angle measurements, and surface energy analysis), we have found that the changes in the wetting properties originate from the different surface structures of the monolayers in different pH environments. From surface energy analysis, we found that the disperse components of the surface energy on such SAMs predominate after treatment with pH 1 water, whereas the polar components of the surface energy on such SAMs predominate after treatment with pH 13 water. It is greatly anticipated that this line of research will provide new insight into the mechanism behind pH-responsive properties, facilitating the design and synthesis of new surface-active molecules for the fabrication of pH-responsive functional surfaces.

Self-assembled monolayers of dendron thiols for electrodeposition of gold nanostructures: toward fabrication of superhydrophobic/superhydrophilic surfaces and pH-responsive surfaces.

This paper describes the fabrication of surfaces with different wettability, superhydrophobic/superhydrophilic, and pH-responsive properties. We used a self-assembled monolayer (SAM) of a dendron thiol as the underlying surface for electrodeposition of gold nanostructures. After this modification with a SAM of n-dodecanethiol or 11-mercaptoundecanol, the surface shows remarkable superhydrophobic properties with a contact angle of about 155 degrees and a tilt angle of less than 2 degrees or superhydrophilic properties with a contact angle of about 0 degrees , respectively. Moreover, a large-scale pH-responsive surface was obtained by modification with 2-(11-mercaptoundecanamido)benzoic acid (7) (MUABA). The pH-responsive behavior was amplified by using rough surfaces.