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Olfactory ensheathing cells (OECs) are unique glial cells with axonal growth-promoting properties in the olfactory epithelium and olfactory bulb, covering the entire length of the olfactory nerve. The proliferation of OECs is necessary for the formation of the presumptive olfactory nerve layer (ONL) during development and OECs transplantation. However, the molecular mechanism underlying the regulation of OEC proliferation in the ONL still remains unknown. In the present study, we examined the role of sphingosine 1-phosphate (S1P) and S1P receptors (S1PRs) on OEC proliferation. Initially, reverse transcription-PCR (RT-PCR), western blot and immunostaining revealed that S1PRs were highly expressed in the OECs in vitro and in vivo. Furthermore, we found that S1P treatment promoted the proliferation of primary cultured OECs mediated by S1PR1. Mechanistically, yes-associated protein (YAP) was required for S1P-induced OEC proliferation through RhoA signaling. Finally, conditional knockout of YAP in OECs reduced OEC proliferation in ONL, which impaired the axonal projection and growth of olfactory sensory neurons, and olfactory functions. Taken together, these results reveal a previously unrecognized function of S1P/RhoA/YAP pathway in the proliferation of OECs, contributing to the formation of ONL and the projection, growth, and function of olfactory sensory neurons during development.

Aims Autophagy has been regarded as a promising therapeutic target for spinal cord injury (SCI). Erythropoietin (EPO) has been demonstrated to exhibit neuroprotective effects in the central nervous system (CNS); however, the molecular mechanisms of its protection against SCI remain unknown. This study aims to investigate whether the neuroprotective effects of EPO on SCI are mediated by autophagy via AMP-activated protein kinase (AMPK) signaling pathways. Methods Functional assessment and Nissl staining were used to investigate the effects of EPO on SCI. Expressions of proteins were detected by Western blot and immunohistochemistry. Results Treatment with EPO significantly reduced the loss of motor neurons and improved the functional recovery following SCI. Erythropoietin significantly enhanced the SCI-induced autophagy through activating AMPK and inactivating mTOR signaling. The inhibitor of AMPK, compound C, could block the EPO-induced autophagy and beneficial action on SCI, whereas the activator of AMPK, metformin, could mimic the effects of EPO. In the in vitro studies, EPO enhanced the hypoxia-induced autophagy in an AMPK-dependent manner. Conclusions The AMPK-dependent induction of autophagy contributes to the neuroprotection of EPO on SCI.

Polymeric hydrogels have been increasingly studied for wound sealants, adhesives, hemostats, and dressings, however, multi-component gelation, adhesion-causing tissue damage, inefficient hemostasis, and skin scarring in wound healing hamper their advances. So it is urgent to develop multifunctional single-component polymeric hydrogels with benign tissue detachment, high performance hemostasis, and scarless wound healing attributes. Herein, a dopamine-modified poly(l-glutamate) hydrogel at an ultralow concentration of 0.1 wt% is serendipitously constructed by physical treatments, in which a gelation mechanism is disclosed via oxidative catechol-crosslinking and sequential dicatechol-carboxyl hydrogen-bonding interactions. The covalent/H-bonding co-crosslinked and highly negative-charged networks enable the polypeptide hydrogels thermo-, salt-, urea-resistant, self-healing, injectable, and adhesive yet detachable. In vitro and in vivo assays demonstrate they have superior biocompatibility with ≈0.5% hemolysis and negligible inflammation. The polypeptide/graphene oxide hybrid hydrogel performs fast and efficient hemostasis of 12 s and 1.4% blood loss, surpassing some hydrogels and commercial counterparts. Remarkably, the polypeptide hydrogels achieve scarless and full wound healing and regenerate thick dermis with some embedded hair follicles within 14 days, presenting superior full-thickness wound healing and skin scar-preventing capabilities. This work provides a simple and practicable method to construct multifunctional polypeptide hemostatic and healing hydrogels that overcome some above-mentioned hurdles.

Two kinds of coordinated and covalent glycopolypeptide hydrogels are fabricated, which present tunable tissue adhesion strength, microporous structure, and lower hemolysis. The large microporous hydrogels achieve superior hemostasis and regenerate thick dermis/epidermis with some hair follicles during wound healing. Significantly, this work discloses the correlation of microstructure‐hemostasis‐wound healing, guiding the design of high‐performance hydrogels‐based hemostatic and healing adhesives and dressings.

Graphene has attracted great interest for its uses in tissue regeneration. Multilayered graphene hydrogel (MGH) membranes show great potential as barrier membranes in guided bone regeneration. However, when using the conventional methyl methacrylate-embedding process, the MGH membrane swells and loses its natural form, which seriously limits the observation of bone regeneration. A rapid embedding method is developed by adding the cross-linker tetra(ethylene glycol)diacrylate and increasing the polymerization temperature (45 °C) and initiator concentration (64% benzoyl peroxide in penetration liquid). By the rapid embedding method, the shape and properties of the MGH membrane can be well preserved, and the bone tissue can also be well embedded. The resulting blocks have uniform hardness, which makes it possible to obtain thin sections using a cutting and grinding procedure. The rapid embedding method has no significant effect on the conventional methods of bone regeneration detection. The interface between the MGH membrane and new bone tissue can be clearly observed. This new hard-tissue-embedding method can lead to better observation of the interaction between bone and graphene, providing an optimized experimental technology for the study of hard tissue regeneration with graphene in the future.

Adrenoreceptors (ARs) are widely expressed and play essential roles throughout the body. Different subtype adrenoceptors elicit distinct effects on cell proliferation, but knowledge remains scarce about the subtype-specific effects of β2-ARs on the proliferation of embryonic pluripotent stem (PS) cells that represent different characteristics of proliferation and cell cycle regulation with the somatic cells. Herein, we identified a β2-AR/AC/cAMP/PKA signaling pathway in embryonic PS cells and found that the pathway stimulation inhibited proliferation and cell cycle progression involving modulating the stem cell growth and cycle regulatory machinery. Embryonic stem (ES) cells and embryonal carcinoma stem (ECS) cells expressed functional β-ARs coupled to AC/cAMP/PKA signaling. Agonistic activation of β-ARs led to embryonic PS cell cycle arrest and proliferation inhibition. Pharmacological and genetic analyzes using receptor subtype blocking and RNA interference approaches revealed that this effect selectively depended on β2-AR signaling involving the regulation of AKT, ERK, Rb, and Cyclin E molecules. Better understanding of the effects of β2-ARs on embryonic PS cell proliferation and cycle progression may provide new insights into stem cell biology and afford the opportunity for exploiting more selective ligands targeting the receptor subtype for the modulation of stem cells.

The probability hypothesis density (PHD) filter is a practical alternative to the optimal Bayesian multiple-targets filter based on random finite sets (RFS). It propagates the posterior intensity of the random sets of targets. In this paper, we apply the PHD filter to track a random number of moving targets in visual sequences. The PHD filter is implemented using a Gaussian mixture. Obtaining the PHD only for one visual frame at a time remains a challenge. To meet this challenge, we propose a method to approximate the posterior intensity using feature measurement. To improve the representability of tracking target, we adopt an adaptive weight to fuse the color and local binary pattern (LBP) features which are extracted by the Monte Carlo method. Experimental results demonstrate the effectiveness of our method. © 2014 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.

In this paper, three kinds of memristors with memristance functions obtained from the Chebyshev polynomials are used in the Muthuswamy-Chua system, which has only three circuit elements: a linear passive inductor, a linear passive capacitor and a nonlinear active memristor. We use multivariable second-order polynomial functions of current and memristor state for the internal state function of the memristor. This enables our system to generate not only double-scroll but also four-scroll attractors. Systematic studies of chaotic behavior in these systems are performed using phase portraits, bifurcation diagrams and Lyapunov exponents. Simulation results show that all these systems exhibit chaotic behavior over a range of control parameters. Copyright © 2014 John Wiley & Sons, Ltd.

The construction of different types of substituted arenes was demonstrated through the photocyclization of 2-(fur-3-yl)ethenylarenes using a 3-furyl group as an isopropenyl equivalent synthon in the photocyclization reaction. The furan portion of the photocyclization intermediate could be fragmented via a base-induced elimination reaction to yield a series of substituted polyaromatics, including naphthalene, benzofuran, benzothiophene, phenanthrene, phenalene, acenaphthene, and triphenylene. Using different reagents, this method made it possible to introduce methyl or 2-hydroxyethyl groups as substituents at specific positions in these arenes.

A 53-year-old man presented with a 1-week history of the acute onset of low back pain and fatigue. Physical examination showed decreased breath sounds over both lower lungs. Chest radiography revealed bilateral pleural effusions. A full blood count showed leucocytosis (white cell count 11AE5 · 10/l), anaemia (haemoglobin concentration 80 g/l) and thrombocytopenia (platelet count 103 · 10/l). Biochemical tests showed elevated serum creatinine (185AE6 lmol/l) and lactate dehydrogenase (2518 iu/l). Bone marrow examination disclosed hypercellularity with increased myeloblasts. Flow cytometric immunophenotyping of bone marrow cells showed expression of CD34, CD33 and CD13, but not of CD14, CD3, CD10 or CD20. Cytogenetic study with a G banding technique showed t(8;21)(q22;q22) and loss of Y (top). Based on morphology, surface markers and cytogenetic studies, a diagnosis of acute myeloid leukaemia with recurrent genetic abnormality was made. He was treated with induction chemotherapy with idarubicin 12 mg/m from day 1 to day 3, and cytarabine 100 mg/m from day 1 to day 7. He achieved complete haematological remission as assessed by bone marrow and peripheral blood examination. His pleural effusion, however, did not resolve. Pleural fluid (bottom left) showed large blasts positive for CD34, CD33, and CD13 with homogenous salmon-colored granules and vacuoles. A normal karyotype of pleural effusion cells was shown by a G banding technique, but fluorescence in situ hybridization analysis using an AML1 (red)/ ETO (green) dual-fusion probe was positive (bottom right), indicating t(8;21)(q22;q22) and RUNX1-RUNX1T1 fusion. After re-induction with high dose cytarabine the pleural effusion disappeared. Having a HLA-matched sibling donor, he underwent allogeneic haematopoietic stem cell transplantation with reduced intensity conditioning. One year later, he is now free of disease and has limited chronic graft-versus-host disease. Leukaemic pleural effusion in acute myeloid leukaemia is rare. In this patient, leukaemic cells in the bone marrow and effusion fluid belonged to the same clone, as showed by presence of t(8;21)(q22;q22). Complete remission in the bone marrow with persistent disease in the pleural cavity is unusual.