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It has recently been reported that Parkinson's disease (PD) is preceded and accompanied by daytime sleep attacks, nocturnal insomnia, REM sleep behaviour disorder, hallucinations and depression, symptoms which are frequently as troublesome as the motor symptoms of PD. All these symptoms are present in narcolepsy, which is linked to a selective loss of hypocretin (Hcrt) neurons. In this study, the Hcrt system was examined to determine if Hcrt cells are damaged in PD. The hypothalamus of 11 PD (mean age 79 +/- 4) and 5 normal (mean age 77 +/- 3) brains was examined. Sections were immunostained for Hcrt-1, melanin concentrating hormone (MCH) and alpha synuclein and glial fibrillary acidic protein (GFAP). The substantia nigra of 10 PD brains and 7 normal brains were used for a study of neuromelanin pigmented cell loss. The severity of PD was assessed using the Hoehn and Yahr scale and the level of neuropathology was assessed using the Braak staging criteria. Cell number, distribution and size were determined with stereologic techniques on a one in eight series. We found an increasing loss of hypocretin cells with disease progression. Similarly, there was an increased loss of MCH cells with disease severity. Hcrt and MCH cells were lost throughout the anterior to posterior extent of their hypothalamic distributions. The percentage loss of Hcrt cells was minimal in stage I (23%) and was maximal in stage V (62%). Similarly, the percentage loss of MCH cells was lowest in stage I (12%) and was highest in stage V (74%). There was a significant increase (P = 0.0006, t = 4.25, df = 15) in the size of neuromelanin containing cells in PD patients, but no difference in the size of surviving Hcrt (P = 0.18, t = 1.39, df = 14) and MCH (P = 0.28, t = 1.39, df = 14) cells relative to controls. In summary, we found that PD is characterized by a massive loss of Hcrt neurons. Thus, the loss of Hcrt cells may be a cause of the narcolepsy-like symptoms of PD and may be ameliorated by treatments aimed at reversing the Hcrt deficit. We also saw a substantial loss of hypothalamic MCH neurons. The losses of Hcrt and MCH neurons are significantly correlated with the clinical stage of PD, not disease duration, whereas the loss of neuromelanin cells is significantly correlated only with disease duration. The significant correlations that we found between the loss of Hcrt and MCH neurons and the clinical stage of PD, in contrast to the lack of a relationship of similar strength between loss of neuromelanin containing cells and the clinical symptoms of PD, suggests a previously unappreciated relationship between hypothalamic dysfunction and the time course of the overall clinical picture of PD.

Hypertrophic scars are pathological scars that result from abnormal responses to trauma, and could cause serious functional and cosmetic disability. To date, no optimal treatment method has been established. A variety of cell types are involved in hypertrophic scar formation after wound healing, but the underlying molecular mechanisms and cellular origins of hypertrophic scars are not fully understood. Macrophages are major effector cells in the immune response after tissue injury that orchestrates the process of wound healing. Depending on the local microenvironment, macrophages undergo marked phenotypic and functional changes at different stages during scar pathogenesis. This review intends to summarize the direct and indirect roles of macrophages during hypertrophic scar formation. The in vivo depletion of macrophages or blocking their signaling reduces scar formation in experimental models, thereby establishing macrophages as positive regulatory cells in the skin scar formation. In the future, a significant amount of attention should be given to molecular and cellular mechanisms that cause the phenotypic switch of wound macrophages, which may provide novel therapeutic targets for hypertrophic scars.

A new nanocomposite system based on Fe3O4 nanoparticles confined in three-dimensional (3D) dual-mode cubic porous carbon is developed using the nanocasting and wet-impregnation methods to assess its performance as an anode for lithium-ion batteries. Several Fe3O4 precursor concentrations are chosen to optimize and determine the best-performing nanocomposite composition. The cubic mesoporous carbon CMK-9 offers a better ability for the Fe3O4 nanoparticles to be accommodated inside the mesopores, efficiently buffering the variation in volume and equally enhancing electrode/electrolyte contact for rapid charge and mass transfer. Among the prepared nanocomposites, the Fe3O4(13)@C9 anode delivers an excellent reversible discharge capacity of 1222 mA h g−1 after 150 cycles at a current rate of 100 mA g−1, with a capacity retention of 96.8% compared to the fourth cycle (1262 mA h g−1). At a higher current rate of 1000 mA g−1, the nanocomposite anode offers a superior discharge capacity of 636 mA h g−1 beyond 300 cycles. The present study reveals the use of a 3D mesoporous carbon material as a scaffold for anchoring Fe3O4 nanoparticles with impressive potential as an anode for new-generation lithium-ion batteries. [ABSTRACT FROM AUTHOR]

Solving well-structured problems often requires using considerable related concepts which are usually scattered and introduced throughout different learning units of a subject. In addition, poor learning of related concepts of preceding units may block the learning of subsequent units, and eventually leads to the inability to solve well-structured problems of a subject. Thus, this work proposes using across-unit diagnostic feedback, which can identify weak concepts not only within a unit but also in different units. Furthermore, the provided feedback can be used to recommend remedial learning paths for students, and inform the students the priority of the paths to understand which weak unit should be remedied first and which weak concepts within a unit should be remedied first. Students can refer to the instructions and use the provided corresponding remedial materials to conduct remedial learning in a systematic way. To discriminate the learning effect among various feedback types, this project will compare the proposed system, the Across-Unit Diagnostic Feedback System (AUDFS), with two other systems, the Single-Unit Diagnostic Feedback System (SUDFS) and the Traditional Feedback System (TFS). Experiment results show that the proposed system significantly enhanced learning achievement and the ability to solve well-structured problems for students. The mean student retention time of the proposed system is significantly higher than that of other systems, indicating that the proposed system enables sustained connection between students and the system. Additionally, positive correlations exist between student retention time of the proposed system and student post-test scores. Through a questionnaire and interviews, most students expressed positive attitudes to the proposed system.

Osteoporosis is a metabolic bone disease characterized by a decrease in bone mass and degradation of the bone microstructure, which increases bone fragility and fracture risk. However, the molecular mechanisms of osteoporosis remain unclear. Long non-coding RNAs (lncRNAs) have become important epigenetic regulators controlling the expression of genes and affecting multiple biological processes. Accumulating evidence of the involvement of lncRNAs in bone remolding has increased understanding of the molecular mechanisms underlying osteoporosis. This review aims to summarize recent progress in the elucidation of the role of lncRNAs in bone remodeling, and how it contributes to osteoblast and osteoclast function. This knowledge will facilitate the understanding of lncRNA roles in bone biology and shed new light on the modulation and potential treatment of osteoporosis.

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, play an important role in cellular communication during skeletal growth and homeostasis. Bioactive molecules carried by EVs are transported to neighboring and distant cells to trigger a series of signaling cascades influencing bone homeostasis. The bioactive activities of osteoclast-derived EVs include regulation of osteoclastogenesis and osteoclast–osteoblast communication. As osteoclast-derived EVs have the potential to regulate osteoclasts and osteoblasts, their application in osteoporosis and other bone metabolic disorders is currently under investigation. However, very few reviews of osteoclast-derived EVs in bone remodeling regulation have yet been published. This article aims to review recent advances in this field, summarizing a new regulator of osteoclastogenesis and osteoclast–osteoblast communication mediated by osteoclast-derived EVs. We will analyze the major challenges in the field and potential for the therapeutic application of EVs.