Extracellular α-synuclein is important in the pathogenesis of Parkinson disease (PD) and also as a potential biomarker when tested in the cerebrospinal fluid (CSF). The performance of blood plasma or serum α-synuclein as a biomarker has been found to be inconsistent and generally ineffective, largely due to the contribution of peripherally derived α-synuclein. In this study, we discovered, via an intracerebroventricular injection of radiolabeled α-synuclein into mouse brain, that CSF α-synuclein was readily transported to blood, with a small portion being contained in exosomes that are relatively specific to the central nervous system (CNS). Consequently, we developed a technique to evaluate the levels of α-synuclein in these exosomes in individual plasma samples. When applied to a large cohort of clinical samples (267 PD, 215 controls), we found that in contrast to CSF α-synuclein concentrations, which are consistently reported to be lower in PD patients compared to controls, the levels of plasma exosomal α-synuclein were substantially higher in PD patients, suggesting an increased efflux of the protein to the peripheral blood of these patients. Furthermore, although no association was observed between plasma exosomal and CSF α-synuclein, a significant correlation between plasma exosomal α-synuclein and disease severity (r=0.176, p=0.004) was observed, and the diagnostic sensitivity and specificity achieved by plasma exosomal α-synuclein were comparable to those determined by CSF α-synuclein. Further studies are clearly needed to elucidate the mechanism involved in the transport of CNS α-synuclein to the periphery, which may lead to a more convenient and robust assessment of PD clinically.

Wild relatives of crops are an important source of genetic diversity for agriculture, but their gene repertoire remains largely unexplored. We report the establishment and analysis of a pan-genome of Glycine soja, the wild relative of cultivated soybean Glycine max, by sequencing and de novo assembly of seven phylogenetically and geographically representative accessions. Intergenomic comparisons identified lineage-specific genes and genes with copy number variation or large-effect mutations, some of which show evidence of positive selection and may contribute to variation of agronomic traits such as biotic resistance, seed composition, flowering and maturity time, organ size and final biomass. Approximately 80% of the pan-genome was present in all seven accessions (core), whereas the rest was dispensable and exhibited greater variation than the core genome, perhaps reflecting a role in adaptation to diverse environments. This work will facilitate the harnessing of untapped genetic diversity from wild soybean for enhancement of elite cultivars.

The PI3 K/AKT/mTOR signalling pathway plays an important role in the regulation of signal transduction and biological processes such as cell proliferation, apoptosis, metabolism and angiogenesis. Compared with those of other signalling pathways, the components of the PI3K/AKT/mTOR signalling pathway are complicated. The regulatory mechanisms and biological functions of the PI3K/AKT/mTOR signalling pathway are important in many human diseases, including ischaemic brain injury, neurodegenerative diseases, and tumours. PI3K/AKT/mTOR signalling pathway inhibitors include single-component and dual inhibitors. Numerous PI3K inhibitors have exhibited good results in preclinical studies, and some have been clinically tested in haematologic malignancies and solid tumours. In this review, we briefly summarize the results of research on the PI3K/AKT/mTOR pathway and discuss the structural composition, activation, communication processes, regulatory mechanisms and biological functions of the PI3K/AKT/mTOR signalling pathway in the pathogenesis of neurodegenerative diseases and tumours.

Background: Despite the large volume of research dedicated to health-related behavior change, chronic disease costs continue to rise, thus creating a major public health burden. Health literacy, the ability to seek, understand, and utilize health information, has been identified as an important factor in the course of chronic conditions. Little research has been conducted on the relationship between health literacy and health-related behaviors and health status in elderly Chinese. The aim of this study was to elucidate the relationship between health literacy and health-related behaviors and health status in China. Methods: The subjects enrolled in this study were selected based on a stratified cluster random sampling design. Information involving >4500 older adults in 44 pension institutions in Urumqi, Changji, Karamay, and Shihezi of Xinjiang between September 2011 and June 2012 was collected. The Chinese Citizen Health Literacy Questionnaire (China Health Education Centre, 2008) and a Scale of the General Status were administered and the information was obtained through face-to-face inquiries by investigators. A total of 1452 respondents met the inclusion criteria. A total of 1452 questionnaires were issued and the valid response rate was 96.14% (1396 of 1452). Factors affecting health literacy and the relationship to health literacy were identified by one-way ANOVA and a multiple linear regression model. Results: The average health literacy level of the elderly in nursing homes was relatively low (71.74 ± 28.35 points). There were significant differences in the health literacy score among the factors of age, gender, race, education level, household income, marital conditions, and former occupation (p < 0.001). The health literacy score was significantly associated with smoking, drinking, physical exercise, and health examination (p < 0.001). The elderly with higher health literacy scores were significantly less likely to have risky behaviors (smoking, regular drinking, and lack of physical exercise), and in turn significantly more likely to undergo health examinations regularly, report good self-rated health, and significantly more likely to access sufficient health information from multiple sources (p < 0.001). No differences were noted between the health literacy score and BMI (p > 0.05). Multiple linear regression analysis showed that the independent influencing factors of health literacy included education level, race, former occupation, household income, age, physical exercise, health examination, smoking, and health information access (p < 0.001). Conclusions: Health literacy was significantly associated with health-related behaviors in elderly Chinese. Further longitudinal studies are needed to help confirm that improving health literacy in the elderly may be effective in changing health-related behaviors. To reduce risky habits, educational interventions to improve health literacy should be simultaneously conducted in health promotion work.

Overexpression of Wnt10b from the osteocalcin promoter in transgenic mice increases postnatal bone mass. Increases in osteoblast perimeter, mineralizing surface, and bone formation rate without detectable changes in pre-osteoblast proliferation, osteoblast apoptosis, or osteoclast number and activity suggest that, in this animal model, Wnt10b primarily increases bone mass by stimulating osteoblastogenesis.Introduction: Wnt signaling regulates many aspects of development including postnatal accrual of bone. Potential mechanisms for how Wnt signaling increases bone mass include regulation of osteoblast and/or osteoclast number and activity. To help differentiate between these possibilities, we studied mice in which Wnt10b is expressed specifically in osteoblast lineage cells or in mice devoid of Wnt10b. Materials and Methods: Transgenic mice, in which mouse Wnt10b is expressed from the human osteocalcin promoter (Oc-Wnt10b), were generated in C57BL/6 mice. Transgene expression was evaluated by RNase protection assay. Quantitative assessment of bone variables was done by radiography, CT, and static and dynamic histomorphometry. Mechanisms of bone homeostasis were evaluated with assays for BrdU, TUNEL, and TRACP5b activity, as well as serum levels of C-terminal telopeptide of type I collagen (CTX). The endogenous role of Wnt10b in bone was assessed by dynamic histomorphometry in Wnt10b −/− mice. Results: Oc-Wnt10b mice have increased mandibular bone and impaired eruption of incisors during postnatal development. Analyses of femoral distal metaphyses show significantly higher BMD, bone volume fraction, and trabecular number. Increased bone formation is caused by increases in number of osteoblasts per bone surface, rate of mineral apposition, and percent mineralizing surface. Although number of osteoclasts per bone surface is not altered, Oc-Wnt10b mice have increased total osteoclast activity because of higher bone mass. In Wnt10b −/− mice, changes in mineralizing variables and osteoblast perimeter in femoral distal metaphyses were not observed; however, bone formation rate is reduced because of decreased total bone volume and trabecular number. Conclusions: High bone mass in Oc-Wnt10b mice is primarily caused by increased osteoblastogenesis, with a minor contribution from elevated mineralizing activity of osteoblasts.

Conductive hydrogels have emerged as promising material candidates for epidermal sensors due to their similarity to biological tissues, good wearability, and high accuracy of information acquisition. However, it is difficult to simultaneously achieve conductive hydrogel-based epidermal sensors with reliable healability for long-term usage, robust mechanical property, environmental degradability for decreased electronic waste, and sensing capability of the physiological stimuli and the electrophysiological signals. Herein, we propose the synthesis strategy of a multifunctional epidermal sensor based on the highly stretchable, self-healing, degradable, and biocompatible nanocomposite hydrogel, which is fabricated from the conformal coating of a MXene (Ti3C2T x ) network by the hydrogel polymer networks involving poly­(acrylic acid) and amorphous calcium carbonate. The epidermal sensor can be employed to sensitively detect human motions with the fast response time (20 ms) and to serve as electronic skins for wirelessly monitoring the electrophysiological signals (such as the electromyogram and electrocardiogram signals). Meanwhile, the multifunctional epidermal sensor could be degraded in phosphate buffered saline solution, which could not cause any pollution to the environment. This line of research work sheds light on the fabrication of the healable, degradable, and electrophysiological signal-sensitive conductive hydrogel-based epidermal sensors with potential applications in human–machine interactions, healthy diagnosis, and smart robot prosthesis devices.

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Transiliac bone biopsies were obtained from 55 women treated with teriparatide or placebo for 12-24 months. We report direct evidence that modeling bone formation at quiescent surfaces was present only in teriparatide-treated patients and bone formation at remodeling sites was higher with teriparatide than placebo.Introduction: Recombinant teriparatide [human PTH(1-34)], a bone formation agent for the treatment of osteoporosis when given once daily subcutaneously, increases biochemical markers of bone turnover and activation frequency in histomorphometry studies. Materials and Methods:We studied the mechanisms underlying this bone-forming action of teriparatide at the basic multicellular unit by the appearance of cement lines, a method used to directly classify surfaces as modeling or remodeling osteons, and by the immunolocalization of IGF-I and IGF-II. Transiliac bone biopsies were obtained from 55 postmenopausal women treated with teriparatide 20 or 40 g or placebo for 12-24 months (median, 19.8 months) in the Fracture Prevention Trial. Results: A dose-dependent relationship was observed in modeling and mixed remodeling/modeling trabecular hemiosteons. Trabecular and endosteal hemiosteon mean wall thicknesses were significantly higher in both teriparatide groups than in placebo. There was a dose-dependent relationship in IGF-II immunoreactive staining at all bone envelopes studied. The greater local IGF-II presence after treatment with teriparatide may play a key role in stimulating bone formation. Conclusions: Direct evidence is presented that 12-24 months of teriparatide treatment induced modeling bone formation at quiescent surfaces and resulted in greater bone formation at remodeling sites, relative to placebo.