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Erziehungswissenschaftliche Revue (EWR) 12 (2013) 4, Rezension von: Maren Goltz: Musikstudium in der Diktatur, Das Landeskonservatorium der Musik / die Staatliche Hochschule für Musik Leipzig in der Zeit des Nationalsozialismus 1933-1945, Tw. zugl. U Lpz, Diss. 2012: Studien z. Ge. d. Landeskonservatoriums d. Musik zu Lpz. im Nationalsozialismus, Stuttgart: Steiner 2013 (462 S.; ISBN 978-3-515-10337-4; 74,00 EUR)

Jie Tang,1 Liqun Zhu,1 Yuejiao Huang,2,3 Lixiang Yang,4 Dangen Ge,5 Zhengyu Hu,6 Chun Wang1 1Department of Oncology, Liyang People’s Hospital, Liyang, 213300, People’s Republic of China; 2Medical School, Nantong University, Nantong, 226019, People’s Republic of China; 3Department of Medical Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, 226399, People’s Republic of China; 4Department of Neurosurgery, Affiliated Zhongda Hospital of Southeast University, Nanjing, 210009, People’s Republic of China; 5Department of Pharmacy, Liyang People’s Hospital, Liyang, 213300, People’s Republic of China; 6Department of General Surgery, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of Medicine, Shanghai, 200072, People’s Republic of ChinaCorrespondence: Chun WangDepartment of Oncology, Liyang People’s Hospital, 70 Jianshe Road, Liyang, Jiangsu, 213300, People’s Republic of ChinaEmail zlkwangchun@163.comObjective: Anal canal cancer is a rare malignancy with increasing incidence in recent times. This study aimed to develop two nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with anal canal cancer.Methods: Information of patients with anal canal cancer from 2004 to 2015 was extracted from the surveillance, epidemiology, and end results (SEER) database. Cox analysis was used to select the risk factors for prognosis, and nomograms were constructed using the R software. The C-index, area under the curve (AUC) of time-dependent receiver operating characteristic (ROC) curves, calibration plot and decision curve analysis (DCA) were used to assess the clinical utility of the nomograms.Results: A total of 2458 patients with malignant tumours of the anal canal were screened out. Sex, age, marital status, histological type, grade, tumour size, AJCC stage, SEER stage and chemotherapy were independent prognostic factors for OS, whereas sex, age, race, histological type, grade, tumour size, AJCC stage, SEER stage and radiotherapy were independent prognostic factors for CSS. In the training cohort, the C-index value for OS nomogram was 0.73 (95% CI, 0.69– 0.77), and the AUC values that predicted the 1-, 3- and 5-year survival rates were 0.764, 0.758 and 0.760, respectively, whereas the C-index value for CSS nomogram model was 0.74 (95% CI, 0.69– 0.79), and the AUC values were 0.763, 0.769 and 0.763, respectively. The calibration plot and DCA curves demonstrated good prediction performance of the model in both the training and validation cohorts.Conclusion: The established nomogram is a visualisation tool that can effectively predict the OS and CSS of patients with anal canal cancer.Keywords: anal canal cancer, cancer specific survival, nomogram, overall survival, prognosis

Yongan Wang,1,* Na Li,1,* Qiuyi Li,1 Zirui Liu,1 Yalan Li,1 Jingwei Kong,1 Ruijuan Dong,2 Dongyu Ge,2 Jie Li,3 Guiying Peng1 1Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Experimental Teaching Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Respiratory Medicine, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guiying Peng; Jie Li Email penggy@bucm.edu.cn; lijie2007@126.comPurpose: Chronic obstructive pulmonary disease (COPD), a prevalent obstructive airway disease, has become the third most common cause of death globally. Xuanbai Chengqi decoction (XBCQ) is a traditional Chinese medicine prescription for the acute exacerbation of COPD. Here, we aimed to reveal the therapeutic effects of XBCQ administration and its molecular mechanisms mediated by Th17/Treg balance and gut microbiota.Methods: We determined the counts of Th17 and Treg cells in the serum of 15 COPD and 10 healthy subjects. Then, cigarette smoke extract-induced COPD mice were gavaged with low, middle, and high doses of XBCQ, respectively. Weight loss, pulmonary function and inflammation, Th17/Treg ratio, and gut microbiota were measured to evaluate the efficacy of XBCQ on COPD.Results: COPD patients had a higher Th17/Treg ratio in the serum than healthy controls, which was consistent with the results in the lung and colon of COPD mice. The middle dose of XBCQ (M-XBCQ) significantly decreased the weight loss and improved the pulmonary function (FEV0.2/FVC) in COPD mice. Moreover, M-XBCQ alleviated lung inflammation by rectifying the Th17/Treg imbalance, reducing the expressions of TNF-α, IL-1β, and MMP-9, and suppressing inflammatory cells infiltration. Meanwhile, M-XBCQ greatly improved the microbial homeostasis in COPD mice by accumulating probiotic Gordonibacter and Akkermansia but inhibiting the growth of pathogenic Streptococcus, which showed significant correlations with pulmonary injury.Conclusion: Oral M-XBCQ could alleviate COPD exacerbations by reshaping the gut microbiota and improving the Th17/Treg balance, which aids in elucidating the mechanism through which XBCQ as a therapy for COPD.Keywords: XBCQ, COPD, intestinal microbiota, Th17/Treg, pulmonary inflammation

Panghua Ding,1,* Jiajing Liu,2,* Qiuyi Li,2 Qiongqiong Lu,3 Junxiang Li,3 Rui Shi,3 Lei Shi,2 Tangyou Mao,3 Dongyu Ge,4 HaiJun Niu,5 Guiying Peng,2 Zhibin Wang3 1Department of Graduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Gastroenterology, Dong Fang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Experimental Teaching Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Anhui Joyfar Pharmaceutical Research Institute Co. Ltd, Hefei, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guiying Peng; Zhibin Wang Email penggy@bucm.edu.cn; wangsanger@126.comBackground: Hudi enteric-coated capsule (HDC) is a Chinese medicine prescribed to treat ulcerative colitis (UC). However, its anti-inflammatory active ingredients and mechanisms remain unknown. This study aimed to investigate the active components of HDC and explore its potential mechanisms against UC by integrating network pharmacology and experimental verification.Methods: A DSS-induced colitis murine model was established to validate the efficacy of HDC by detecting disease activity index (DAI) and histopathological changes. Network pharmacological analysis was performed to identify the active compounds and core targets of HDC for the treatment of UC. The main compounds in HDC were identified by high-performance liquid chromatography. The relative expressions of HDC’s core targets were also determined in vivo. Finally, molecular docking was applied to model the interaction between HDC and target proteins.Results: In an in vivo experiment, HDC, especially the middle-dose HDC, effectively reduced clinical symptoms of UC, including weight loss, bloody stool, and colon shortening. Besides, the severity of colitis was considerably suppressed by HDC as evidenced by reduced DAI scores. A total of 118 active compounds and 69 candidate targets from HDC closely related to UC progression were identified via network pharmacology. Enrichment analysis revealed that the key targets of HDC correlated with the expressions of PTGS2, TNF-α, IL-6, and IL-1β. Meanwhile, these cytokines were enriched in various biological processes through the IL-17/JAK2/STAT3 signaling pathway. The middle-dose HDC contributed more to ameliorating DSS-induced colitis through this signaling pathway than other dosages. Nine components binding to JAK2, STAT3, IL-17 and IL-6 were identified by molecular docking, confirming again the inhibition effects of HDC on the IL-17/JAK2/STAT3 signaling pathway.Conclusion: The HDC treatment, particularly the middle-dose, exerted an anti-UC effect in a multi-component, multi-target, and multi-mechanism manner, especially inhibiting the IL-17/JAK2/STAT3 signaling pathway to downregulate the secretion of proinflammatory cytokines.Keywords: Hudi enteric-coated capsule, ulcerative colitis, network pharmacology, IL-17/JAK2/STAT3 pathway

Di Mei,1,&ast; Xiaolong Guo,2,&ast; Yirong Wang,1 Xiaofei Huang,1 Li Guo,1 Pengfei Zou,3 Delong Ge,1 Xinxin Wang,1 Wenhui Lee,4 Tongyi Sun,1 Zhiqin Gao,1 Yuanyuan Gao3 1School of Life Science and Technology, Shandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering, Shandong Universities Key Laboratory of Biopharmaceuticals, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 2School of Basic Medicine, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 3School of Pharmacy, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 4Key Laboratory of Animal Models and Human Disease Mechanism, Institute of Zoology, Kunming, Yunnan, 650233, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiqin GaoSchool of Life Science and Technology, Shandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering, Shandong Universities Key Laboratory of Biopharmaceuticals, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of ChinaTel +86 5368462066Email zhiqingao2013@163.comYuanyuan GaoSchool of Pharmacy, Weifang Medical University, Baotong Road, Weifang, Shandong Province, 261053, People’s Republic of ChinaTel +86 536 846 2067Email yyg20062006@126.comBackground: The treatment of Staphylococcus aureus (S. aureus)-infected wounds is difficult. It causes extreme pain to tens of thousands of patients and increases the cost of medical care. The antimicrobial peptide OH-CATH30 (OH30) has a good killing activity against S. aureus and can play a role in accelerating wound healing and immune regulation. Therefore, it shows great potential for wound healing.Purpose: The aim of this study was to overcome the short half-life and easy enzymolysis of OH30 by using graphene oxide conjugated with polyethylene glycol to load OH30 (denoted as PGO-OH30), as well as to evaluate its effect on wounds infected by S. aureus.Methods: PGO-OH30 nanoparticles were prepared by π–π conjugation and characterized. Their cell cytotoxicity, cell migration, infectious full-thickness dermotomy models, and histopathology were evaluated.Results: Characterization and cytotoxicity experiments revealed that the PGO-OH30 drug-delivery system had good biocompatibility and excellent drug-delivery ability. Cell-migration experiments showed that PGO-OH30 could promote the migration of human immortalized keratinocytes (HaCaT) cells compared with the control group (P< 0.05). In a mouse model of skin wound infection, PGO-OH30 accelerated skin-wound healing and reduced the amount of S. aureus in wounds compared with the control group (P< 0.05). In particular, on day 7, the number of S. aureus was 100 times lower in the PGO-OH30 group than in the control group.Conclusion: The PGO-OH30 drug-delivery system had good biocompatibility and excellent drug-delivery ability, indicating its good therapeutic effect on a skin wound-infection model.Keywords: OH-CATH30, bacterial infection, graphene oxide, skin wound

1. A refinement has been made on the imperical relation between the oscillational CSS frequencies of a number of hydrides and deuterides of germanium of the type R3GeH(D) and the inductive effect of substituents R. 2. A connection has been found between the inductive constants of substituents in hydrides and deuterides of germanium and silicon, and Taft's polarity constants. 3. A number of organic hydrides and deuterides of germanium have been prepared and an enhanced tendency of allyl germanium compounds to polymerization has been demonstrated.

Studied mostly in developed countries, the increased prevalence of suicide among youth, worldwide, is a preventable public health concern. Guyana, a developing country in South America, has the highest rate of youth death by suicide. Based on the diathesis-stress model, this community-based study aimed to identify both psychiatric and biological factors associated with repeated suicide attempts among high-risk youth. Objective We measured psychiatric symptoms, childhood traumas, and cortisol to identify correlates with recurrent suicide attempts. Method Poisson regression tested the association between psychiatric symptoms, trauma, and cortisol levels on number of suicide attempts among 50 youths from three child welfare orphanages in Guyana. Sixty-six percent were female, and the average age was 14 years. DSM-5 symptom measure was administered and saliva samples collected. Results Fifty percent of the youth endorsed suicide attempt. Within this subsample, a minimum of one and maximum of five suicide attempts were self-reported. Participants' number of suicide attempts was positively associated with number of past traumas, psychosis, and depression symptoms. Conclusion Suicide prevention screening among at-risk youth should target severity of psychosis and depression reports and number of traumatic life experiences.

Hao-cheng Zheng,1,* Yong-an Wang,1,* Zi-rui Liu,1 Ya-lan Li,1 Jing-wei Kong,1 Dong-yu Ge,2 Gui-ying Peng1 1Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 2Experimental Teaching Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gui-ying PengBeijing University of Chinese Medicine, No. 11, East Road North Ring 3rd, Chao-Yang District, Beijing 100029, People’s Republic of ChinaTel +86-010-53912169Email penggy@bucm.edu.cnObjective: In China, lamb and fish are well-known triggers for an asthma attack. Our investigation aims at assessing whether the long-term intake of lamb meat or Basa fish would aggravate pulmonary inflammation as well as exploring changes in the intestinal microbiota and immune cells in asthmatic mice.Materials and Methods: The murine asthmatic model was established by intraperitoneal injection of ovalbumin (OVA) plus aluminum on day 0 and 14 and nebulization of OVA from day 21 to 27. Lamb meat or fish was administered to asthmatic mice by oral gavage from day 0 to 27.Results: Our results showed that long-term consumption of lamb meat or Basa fish in asthmatic mice increased the number of inflammatory cells in bronchoalveolar lavage fluid (BALF), enhanced levels of IL-5, IL-13 in BALF and total IgE in serum, aggravated pulmonary inflammatory cell infiltration and mucus secretion. Long-term oral lamb enhanced the proportion of type 2 innate lymphoid cells (ILC2) from small intestine while it inhibited that of Treg from lung in asthmatic mice. Oral fish showed no remarkable effect on that of ILC2 from lung and small intestine but inhibited that of intestinal Treg in asthmatic mice. What’s more, the chao-1 and observed species richness as well as PD whole tree diversity increased in asthmatic mice while these increments were inhibited after lamb treatment. PCA analysis indicated that there were significant differences in the bacterial community composition after lamb or fish treatment in asthmatic mice. Both lamb and fish treatment enhanced the abundance of colonic Alistipes in asthmatic mice.Conclusion: Collectively, long-term intake of lamb or fish shapes colonic bacterial communities and aggravates pulmonary inflammation in asthmatic mice, which provides reasonable food guidance for asthmatic patients.Keywords: asthma, intestinal microbiota, lamb, fish, ILC2, Treg

Deuterated and fluorinated amorphous silicon-germanium alloys, a-Si, Ge:D, F, were studied by Fourier transform infrared (IR) spectroscopy. No Ge.-F modes are observed. The intensity of the Si-F and Si-F2 modes increases with Ge concentration. So does thae intensity of SiF4 which is trapped as isolated molecules. No DF (IR) or F2 (Raman) is observed. The IR spectra of alloys annealed at 300, 400, 500 and 600° C show that the fluorine in the Si-F and Si-F2 groups and in the SiF4 molecules is in thermochemical equilibrium.

Dan Ge,1,2,* Qiqi Du,1,2,* Bingqing Ran,1,2 Xingyu Liu,1,2 Xin Wang,1,2 Xuehu Ma,1 Fang Cheng,1,3 Bingbing Sun1,21State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, People’s Republic of China; 2Department of Chemical Engineering, Dalian University of Technology, Dalian 116024, People’s Republic of China; 3Department of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian 116024, People’s Republic of China*These authors contributed equally to this work Abstract: Engineered nanomaterials (ENMs) have been widely used in various fields due to their novel physicochemical properties. However, the use of ENMs has led to an increased exposure in humans, and the safety of ENMs has attracted much attention. It is universally acknowledged that ENMs could enter the human body via different routes, eg, inhalation, skin contact, and intravenous injection. Studies have proven that ENMs can cross or bypass the blood–brain barrier and then access the central nervous system and cause neurotoxicity. Until now, diverse in vivo and in vitro models have been developed to evaluate the neurotoxicity of ENMs, and oxidative stress, inflammation, DNA damage, and cell death have been identified as being involved. However, due to various physicochemical properties of ENMs and diverse study models in existing studies, it remains challenging to establish the structure-activity relationship of nanomaterials in neurotoxicity. In this paper, we aimed to review current studies on ENM-induced neurotoxicity, with an emphasis on the molecular and cellular mechanisms involved. We hope to provide a rational material design strategy for ENMs when they are applied in biomedical or other engineering applications.Keywords: engineered nanomaterials, neurotoxicity, oxidative stress, inflammation, DNA damage, cell death

Copper intrauterine device is one of the most adopted contraceptive methods with high effectiveness (over 99 %), low cost, spontaneous reversibility and long-lasting usage. However, the side effects induced from the initial burst release of copper ions (Cu2+) hinder the continuation of the Cu-IUD made of Coarse-Grained Copper (CG Cu). We proposed to tailor the bio-corrosion behaviors of better control of Cu2+ release via the addition of bioactive Mg into the Ultra-Fine Grained (UFG) Bulk Cu. Thus, UFG bulk Cu with 0.4 wt.% Mg was produced via equal-channel angular pressing. The microstructures of the UFG Cu-0.4Mg was observed using electron backscatter diffraction and transmission electron microscopy techniques. The in vitro long-term corrosion behaviors in simulated uterine fluid, cytotoxicity to four cell lines, in vivo biocompatibility and contraceptive efficacy were all studied on CG Cu, UFG Cu and UFG Cu-0.4Mg materials. The results demonstrate that both the ultrafine grains and the addition of bioactive Mg into Cu contribute to the suppression of the burst release of Cu2+ in the initial stage and the maintenance of high level Cu2+ in long-term release. Moreover, the UFG Cu-0.4Mg also exhibited much improved cell and tissue biocompatibility from both the in vitro and in vivo evaluations. Therefore, the contraceptive efficacy of UFG Cu-0.4Mg is still maintained as high as the CG Cu and UFG Cu while the side effects are significantly eased, suggesting the high potential of the UFG Cu-0.4Mg alloy as a new upgrading or alternative material for Cu-IUD. STATEMENT OF SIGNIFICANCE: The side effects from burst release of Cu2+ at the initial implantation stage of Cu-containing intrauterine devices (Cu-IUD) is one of the main drawbacks of these devices. In this work, an ultra-fine-grained Cu (UFG Cu) alloyed with a low amount of bioactive Mg was used for a Cu-IUD. The UFG Cu-0.4Mg alloy exhibited suppressed burst release of Cu2+ at initial implantation, while active Cu2+ release for long-term usage was maintained, comparable to coarse-grained pure Cu. Furthermore, the UFG Cu-0.4Mg alloy displayed significantly improved biocompatibility with human uterus cells and a much decreased inflammatory response within the uterus. Therefore, the side effects from Cu-IUD were eased, while high antifertility efficacy of the UFG Cu-0.4Mg alloy was maintained. The UFG Cu-0.4Mg alloy is promising for Cu-IUD.

Hygroresponsive actuators harness minor fluctuations in the ambient humidity to realize energy harvesting and conversion, thus they are of profound significance in the development of more energy-saving and sustainable systems. However, most of the existing hygroresponsive actuators are only adaptive to wet environments with limited moving directions and shape morphing modes. Therefore, it is highly imperative to develop a hygroresponsive actuator that works in both wet and dry environments. In this work, we present a bidirectional actuator responsive to both wet and dry stimuli. Our strategy relies on the introduction of carbon nanotubes to provide transport channels for water molecules. The actuation is enabled by the rapid transport of water in and out of the system driven by the moist/dry surroundings owing to the transport channels. The resultant actuator demonstrates reconfiguration and locomotion with turnover frequency F = 30 min−1, coupled with the capability of lifting objects 6 times heavier and transporting cargos 63 times heavier than itself. Oscillations (24°) driven by dry air flow in a cantilever display a high frequency (2 Hz) and large amplitude. Furthermore, a touchless electronic device was constructed to output varying signals in response to humid and dry environments. Our work provides valuable guidance and implications for designing and constructing hygroresponsive actuators, and paves the way for next-generation robust autonomous devices to exploit energy from natural resources.

Objective: Suicide is the leading cause of death among youth in Guyana, a low- and middle-income country (LMIC), which globally ranks first in female adolescent suicides over the last decade. Worldwide, Guyana has experienced the largest increase in youth suicide, despite focused public health efforts to reduce suicide. Further, youth in Guyana, who are clients of the orphanage system and have faced early childhood trauma, may have an additive risk for suicide. Guided by an ideation-to-action theoretical framework for suicide prevention, the goal of the proposed research study is to describe and identify risk and protective factor correlates of youth suicidal behaviour among those at highest risk for suicide – orphans who reside in a LMIC institutional setting. Methods: In a preliminary sample of 25 orphan youth, one licensed psychologist and two social workers administered the DSM-5 Level 1 Cross-Cutting Symptom Measure and Behavioural Assessment Schedule for Children, 2nd Edition (BASC-2) during a semi-structured interview. Results: Nine of the 25 (36%) orphans reported a previous suicide attempt. Youth who endorsed suicidal behaviour had clinically elevated interpersonal relations scale scores when compared to youth who did not. Conclusions: Interpersonal skills may be protective for youth at highest risk for suicide.

International audience; Robust, real-time apnea and hypopnea detection for monitoring patients suffering from sleep apnea syndrome (SAS) still represents an open problem due to the effect of noise artifacts, the complexity of respiratory patterns and inter-subject variability. We propose in this study the application of an original multi-feature probabilistic detector (MFPD) for SAS event detection during long-term monitoring recordings on three SAS patients. The nasal pressure signal is used as input to derive a set of respiratory features (variance, peak-to-peak amplitude and total respiration cycle) which are statistically characterized during time and used to provide a mono-feature detection probability in realtime. A centralized fusion approach based on the Kullback-Leibler divergence (KLD), optimally combines these mono-feature distributions in order to produce a final detection. While the optimal feature set selection lies beyond the scope of our study, we illustrate the ability to adapt each feature's weight dynamically to make centralized fusion decisions. The method can be directly applied to data acquired from multiple sensors as long as features are synchronized. Our proposed fusion method achieves a very high sensitivity (94%) as compared with reference thresholding based methods in the literature. © 2019 Creative Commons.

International audience; Breathing rate (BR) is an important physiological indicator monitored for a variety of chronic diseases. Since direct measurement devices are often cumbersome to wear, we hence aim to obtain an accurate estimation of BR using other monitored signals, such as PPG or ECG. However, derived modulations from these signals are highly dependent on patient and activity type, making the task difficult as to switching among the modulations. We have previously proposed respiration quality index(RQI) based selection method to update the optimal modulation in a realtime manner. A fusion strategy has also been proposed by coupling the RQI with a Kalman smoother to further exploit the sinusoidal waveforms observed from different modulations. In the current study, we further investigate the enhancement of model complexity of the Kalman smoother by introducing multiple frequency dynamics. Performances are compared to reference methods (Pimentel2016, Karlen2013) on the Capnobase Benchmark dataset. In particular, our enhanced KS method achieves a median absolute error and 25-75 percentile range of 0.22(0.16 - 0.64) bpm, as compared with 0.35(0.28 0.89) bpm from our previous KS fusion method and 1.1(0.3 2.6) bpm from the best reference method in the literature (Karlen et al. 2013). © 2019 Creative Commons.

Ying Geng,1,* Lili Deng,2,* Dongju Su,1 Jinling Xiao,1 Dongjie Ge,3 Yongxia Bao,1 Hui Jing4 1Department of Respiratory, 2Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, 3Department of Respiratory, The First Hospital of Harbin, 4Department of Emergency, The Second Affiliated Hospital of Harbin Medical University Harbin, Heilongjiang, People’s Republic of China *These authors contributed equally tothis work Background: Variations of microRNA (miRNA) expression profile in hypoxic lung cancer cells have not been studied so far. Therefore, using miRNA microarray technology, this study aimed to study the miRNA expression profile and investigate the potential crucial miRNAs and their target genes in hypoxia-induced human lung adenocarcinoma cells.Materials and methods: Based on miRNA microarray, miRNA expression profiling of hypoxia-induced lung adenocarcinoma A549 cells was obtained. After identification of differentially expressed miRNAs (DE-miRNAs) in hypoxic cells, target genes of DE-miRNAs were predicted, and functional enrichment analysis of targets was conducted. Furthermore, the expression levels of DE-miRNAs and their target genes were validated by real-time quantitative polymerase chain reaction. In addition, using miRNA mimics, the effect of overexpressed DE-miRNAs on A549 cell behaviors (cell proliferation, cell cycle, and apoptosis) was evaluated.Results: In total, 14 DE-miRNAs (nine upregulated miRNAs and five downregulated miRNAs) were identified in hypoxic cells, compared with normoxic cells. Target genes of both upregulated and downregulated miRNAs were enriched in the functions such as chromatin modification, and pathways such as Wnt signaling pathway and transforming growth factor (TGF)-β signaling pathway. The expression levels of several miRNAs and their target genes were confirmed, including hsa-miR-301b/FOXF2, hsa-miR-148b-3p/WNT10B, hsa-miR-769-5p/(SMAD2, ARID1A), and hsa-miR-622. Among them, hsa-miR-301b was verified to regulate FOXF2, and hsa-miR-769-5p was verified to modulate ARID1A. In addition, the overexpression of hsa-miR-301b and hsa-miR-769-5p significantly affected the cell cycle of A549 cells, but not cell proliferation and apoptosis.Conclusion: miRNA expression profile was changed in hypoxia-induced lung cancer cells. Those validated miRNAs and genes may play crucial roles in the response of lung cancer cells to hypoxia. Keywords: hypoxia, lung cancer, A549, microarray, hsa-miR-301b, hsa-miR-769-5p

Control of systems operating in unexplored environments is challenging due to lack of complete model knowledge. Additionally, under measurement noises, data collected from onboard sensors are of limited accuracy. This paper considers imperfect state observations in developing a control strategy for systems moving in unknown environments. First, we include hard constraints in the problem for safety concerns. Given the observed states, the robust myopic control approach learns local dynamics, explores all possible trajectories within the observation error bound, and computes the optimal control action using robust optimization. Finally, we validate the method in an OSIRIS-REx-based asteroid landing scenario., Presented as Paper AAS 18-253 at AAS/AIAA Astrodynamics Specialist Conference, Snowbird, UT, August 2018

INTRODUCTION Suicide is the second leading cause of death among youth worldwide, but low- and middle-income countries (LMICs) account for 78% of all suicides. The LMICs South Africa and Guyana rank high in the global suicide rates. To better understand and prevent suicide among the youth, the present study targets youths at high risk for suicide, in an LMIC, to contextually and representatively identify clinical risk factors for suicide. METHODS One hundred-ninety youths, aged 11-21, separated from biological parents at the time of assessment, in South Africa and Guyana, were administered the Child Behavior Checklist and Behavior Assessment System for Children to assess clinical symptoms. The youths were asked about current suicide ideation and previous attempt(s). Self-report responses to clinical items yielded scale scores for depression, social stress, atypicality, somatization, anxiety, and ADHD. Using an integrative data analytic technique, clinical scale scores were standardized and used to predict suicidal behaviors in a binary logistic regression analysis. RESULTS Approximately 22% of Black South African youths and 60% of Guyanese youths endorsed suicide ideation and attempt or suicide attempt only. In fully adjusted analyses, the odds of atypicality and somatization were 1.96 and 1.67 times greater among the youths who endorsed suicidal ideation when compared with those who did not (p

The Ethnic Density hypothesis posits that living around others from similar ethnic backgrounds reduces the risk of adverse mental health outcomes such as depression. Contrary to this hypothesis, previous work has shown that Hispanic ethnic density is cross-sectionally associated with increased depressive symptom severity among patients hospitalized with an acute coronary syndrome (ACS; myocardial infarction or unstable angina pectoris). To date, no study has examined the prospective association of Hispanic ethnic density on long-term depressive symptom severity following an acute medical event. We prospectively assessed the impact of Hispanic ethnic density on depressive symptoms, 1-year following an ACS event, among Hispanic adult patients. We tested the non-linear association between ethnic density and depressive symptoms to account for inconsistent findings on the ethnic density hypothesis. At the time of an index ACS event (i.e., baseline, N = 326) and 1-year later (N = 252), Hispanic patients from the Prescription Usage, Lifestyle, and Stress Evaluation prospective cohort study completed the Beck Depression Inventory as a measure of depressive symptom severity. Hispanic ethnic density was defined by the percentage of Hispanic residents within each patient���s census tract using data extracted from the American Community Survey Census (2010���2013). Covariates included baseline demographic factors (age, gender, English fluency, education, nativity status), cardiovascular factors (Charlson comorbidity index, left ventricular ejection fraction, Global Registry of Acute Coronary Events 6-month prognostic risk score), and neighborhood factors (residential density, income, and percentage of households receiving public assistance). In an adjusted multivariable linear regression analysis there was a significant curvilinear association between Hispanic ethnic density and depressive symptom severity at 1 year. As Hispanic ethnic density increased from low to moderate density, there was an increase in depressive symptoms, but depressive symptoms slightly declined in census tracts with the highest density of Hispanics. Furthermore, gender significantly moderated the relation between Hispanic ethnic density and 1-year depressive symptom severity, such that Hispanic ethnic density was significantly associated with increased depressive symptom severity for female Hispanic patients with ACS, but not for male Hispanic patients. Previous research suggests that ethnic density may be protective against depression in Hispanic enclaves; however, our findings suggest a non-linear ethnic density effect and an overall more complex association between ethnic density and depression. These data add to a growing body of literature on the effects of sociodemographic and contextual factors on health.

Background: The ethnic density hypothesis suggests that ethnic density confers greater social support and consequently protects against depressive symptoms in ethnic minority individuals. However, the potential benefits of ethnic density have not been examined in individuals who are facing a specific and salient life stressor. Aims: We examined the degree to which the effects of Hispanic ethnic density on depressive symptoms are explained by socioeconomic resources and social support. Methods: Patients with acute coronary syndrome (ACS, N = 472) completed the Beck Depression Inventory (BDI) and measures of demographics, ACS clinical factors and perceived social support. Neighborhood characteristics, including median income, number of single parent households and Hispanic ethnic density, were extracted from the American Community Survey Census (2005–2009) for each patient using his or her geocoded address. Results: In a linear regression analysis adjusted for demographic and clinical factors, Hispanic ethnic density was positively associated with depressive symptoms (β = .09, standard error (SE) = .04, p = .03). However, Hispanic density was no longer a significant predictor of depressive symptoms when neighborhood characteristics were controlled. The relationship of Hispanic density on depressive symptoms was moderated by nativity status. Among US-born patients with ACS, there was a significant positive relationship between Hispanic density and depressive symptoms and social support significantly mediated this effect. There was no observed effect of Hispanic density to depressive symptoms for foreign-born ACS patients. Conclusion: Although previous research suggests that ethnic density may be protective against depression, our data suggest that among patients with ACS, living in a community with a high concentration of Hispanic individuals is associated with constrained social and economic resources that are themselves associated with greater depressive symptoms. These data add to a growing body of literature on the effects of racial or ethnic segregation on health outcomes.

Regular physical activity reduces the risk of adverse events after an acute coronary syndrome (ACS).1 Physical activity level is influenced by neighborhood factors such as racial diversity in the general population,2,3 but the impact of neighborhood factors on physical activity after an ACS is unknown. We therefore prospectively evaluated the relationship of post-ACS physical activity assessed by continuous activity monitors with neighborhood characteristics, including ethnic density, income, female headed households, and racial diversity, in patients enrolled in the Prescription Use, Lifestyle, and Stress Evaluation (PULSE) Study. We included 107 patients enrolled in the PULSE study from February 1, 2009 to June 30, who were monitored with an Actical® (Philips – Respironics, Inc, Bend, Oregon) accelerometer device during the first 45 days following discharge from their ACS. For this analysis, physical activity level was operationalized as the mean maximum 6 minutes of activity during the day (M6m), which has previously been employed in studies of patients with chronic heart failure to summarize the patients’ peak activity level.4, 5 Because the trajectory of physical activity is expected to change after hospital discharge, we calculated the M6m measure at 7, 14, 21, and 28 days post-discharge. Characteristics of neighborhood in which patients resided were determined by geocoding mailing addresses using the ArcGISSM (Arc Geographic Information System) software to map individual patients to census tracts (Figure 1). Twenty patients were excluded, at random, as to not violate an assumption of independence when analyzing nested individual-level and neighborhood-level data. Patients were distributed across 87 census tracts. The current analysis therefore included 87 PULSE patients. From the Census American Community Survey 2005-2009 we extracted four neighborhood characteristics corresponding to each census tract: Neighborhood racial diversity, Hispanic ethnic density, percentage female headed household, and median income.6,7 Neighborhood Racial Diversity Index is derived from the calculated variance of four racial/ethnic categories, Black, White, Asian, and Hispanic, summed together to compute the generalized measure of variance (GV), where higher values reflect a higher degree of racial/ethnic diversity. 8 The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the Institutional Review Board of Columbia University Medical Center and all patients provided informed consent. Figure 1 Demographic mapping of neighborhood racial diversity for Post ACS patients (N = 87). Darker colors indicate census tracts with increased racial heterogeneity. All neighborhood measures were investigated as continuous measures, with exception of neighborhood racial diversity, which was also categorized into quartiles with the highest quartile as reference. Using growth curve model as a base, neighborhood measures and all other covariates were individually added to the model to assess their bivariate associations with estimated physical activity (M6m) at each time point. Subsequent models assessed the independent association of neighborhood diversity with Day 7, 14, 21, and 28 physical activity after adjusting for demographic (age, gender, ethnicity, race, medicaid insurance, and education) clinical (Charlson comorbidity index, the Global Registry of Acute Coronary Events (GRACE) risk score, left ventricular ejection fracture [LVEF], body mass index, and diagnosis of diabetes mellitus) and the above-described neighborhood level predictors. Because day 7 physical activity may differ from patients Day 14, 21, and 28 physical activity, we tested for the interaction of time and time-squared with each of the significant predictors of physical activity. The mean age of participants was 61.8 years, and the self-identified racial-ethnic composition of the patient sample is 62% White, 32% Hispanic, 19% Black, 3% Asian, 14% Other, and 2% multiple race (Table 1). The average GV index was 0.40, indicating that, on average, there is approximately a 40% chance that two randomly selected patients in the “average neighborhood” would belong to different racial-ethnic subgroups. After adjustment for all demographic, clinical, and neighborhood predictors, the linear association between neighborhood racial diversity and predicted peak physical activity remained significant across all time points (p < .008). Table 1 Baseline Characteristics of Study Participants (N=87) and their Bivariate Correlations with Predicted Day 7 Peak Daytime Physical Activity Categorical analyses indicated that the predicted peak physical activity on day 28 post-ACS was on average 41.3% greater for patients living in neighborhoods in the upper quartile of neighborhood racial diversity. In the fully adjusted model, predicted peak physical activity in the most racially diverse neighborhoods was 40.6%, 42.5%, 39.6%, and 32.4% greater compared to that in neighborhood in the lower three quartiles of racial diversity, at Days 7, 14, 21, and 28 post-ACS discharge, respectively. The interaction effect of racial diversity with post-discharge day (both linear and quadratic terms) was statistically significant, indicating that the effect of neighborhood diversity on predicted peak physical activity is not constant over time. The principal finding of this study is that neighborhood racial diversity was independently associated with higher physical activity after an ACS. On average, across all four time-points, the upper quartile of neighborhood racial diversity had greater physical activity outcome than the bottom three quartiles of neighborhood racial diversity. Previous studies have been inconclusive in identifying neighborhood factors associated with physical activity. Some studies suggest that lower census tract income is associated with decreased physical activity.2 On the other hand, high population density has been shown to be positively associated with physical activity. 3 Also, increased residential racial segregation has been found to be associated with decreased physical activity both in the United Kingdom and in the US.3,10 Our results confirm a different association for ACS patients, increased neighborhood level of racial diversity is associated with increased peak physical activity in a largely urban area. Reasons for this association include the possibility that patients who live in racially diverse neighborhoods have differential access to facilities for physical activity, 9 or that their exercise habits are positively influenced by exposure to the physical activity patterns of individuals of varying race and ethnicity. This study was limited to a small number of participants recruited from a single center and only a subset of enrolled patients wore accelerometers. However, there were no differences across baseline characteristics between patients who enrolled in the actigraphy study versus those who did not enroll. In conclusion, these findings suggest that the environment may play an important role in post ACS activity level and merits attention when caring for patients after an ACS.

The Ethnic Density hypothesis posits that living around others from similar ethnic backgrounds reduces the risk of adverse mental health outcomes such as depression. Contrary to this hypothesis, previous work has shown that Hispanic ethnic density is cross-sectionally associated with increased depressive symptom severity among patients hospitalized with an acute coronary syndrome (ACS; myocardial infarction or unstable angina pectoris). To date, no study has examined the prospective association of Hispanic ethnic density on long-term depressive symptom severity following an acute medical event. We prospectively assessed the impact of Hispanic ethnic density on depressive symptoms, 1-year following an ACS event, among Hispanic adult patients. We tested the non-linear association between ethnic density and depressive symptoms to account for inconsistent findings on the ethnic density hypothesis. At the time of an index ACS event (i.e., baseline, N = 326) and 1-year later (N = 252), Hispanic patients from the Prescription Usage, Lifestyle, and Stress Evaluation prospective cohort study completed the Beck Depression Inventory as a measure of depressive symptom severity. Hispanic ethnic density was defined by the percentage of Hispanic residents within each patient's census tract using data extracted from the American Community Survey Census (2010-2013). Covariates included baseline demographic factors (age, gender, English fluency, education, nativity status), cardiovascular factors (Charlson comorbidity index, left ventricular ejection fraction, Global Registry of Acute Coronary Events 6-month prognostic risk score), and neighborhood factors (residential density, income, and percentage of households receiving public assistance). In an adjusted multivariable linear regression analysis there was a significant curvilinear association between Hispanic ethnic density and depressive symptom severity at 1 year. As Hispanic ethnic density increased from low to moderate density, there was an increase in depressive symptoms, but depressive symptoms slightly declined in census tracts with the highest density of Hispanics. Furthermore, gender significantly moderated the relation between Hispanic ethnic density and 1-year depressive symptom severity, such that Hispanic ethnic density was significantly associated with increased depressive symptom severity for female Hispanic patients with ACS, but not for male Hispanic patients. Previous research suggests that ethnic density may be protective against depression in Hispanic enclaves; however, our findings suggest a non-linear ethnic density effect and an overall more complex association between ethnic density and depression. These data add to a growing body of literature on the effects of sociodemographic and contextual factors on health.

International audience; This study aims to detect apnea-bradycardia (AB) episodes from preterm newborns, based on the analysis of electrocardiographic signals (ECG). We propose the use of an auto-regressive (AR) model with undetermined orders to capture all possible linear dependency of the RR interval time series extracted from ECG. An on-line algorithm inspired from the Kalman filtering technique is designed to follow the evolution of the AR model's order distribution. The detection sensitivity (TP/(TP + FN)) reaches 91:5% over a total of 50 episodes with perfect specificity (TN/(FP+TN)=100%). From the clinical point of view, it is essential to achieve reliable early stage detection of AB episodes to enable the initiation of quick nursing actions. Our proposed method achieves a delay of 5:08s 2:90 compared with the experts' off-line annotations, knowing that the mean intervention time (duration from the generation of the alarm to the initiation of manual stimulation) is reported to be 33 seconds from a recent study [5].

Coronary heart disease (CHD) and depression are both highly prevalent in women. Importantly, depression is associated with significantly elevated morbidity and mortality in women with CHD. There are intriguing speculations about biological mechanisms underlying this association, such as endothelial dysfunction, subclinical atherosclerosis, inflammation, and autonomic dysregulation. Social and behavioral mechanisms, such as lack of social support and physical inactivity, have also been shown to play important roles. Unfortunately, many randomized clinical trials of counseling and pharmacologic interventions for depression in patients with CHD have failed to improve cardiovascular outcomes, and in fact have raised the possibility that interventions might be harmful in women. Several recent trials of new treatment strategies, however, have been more effective in improving depressive symptoms and quality of life and deserve further investigation. In this review, we summarize recent findings with regards to the epidemiology, etiology, diagnosis, and management of depression in women diagnosed with CHD.

Psychosocial vulnerabilities may predispose individuals to develop depression after a significant life stressor, such as an acute coronary syndrome (ACS). The aims are (1) to examine the interrelations among vulnerabilities, and their relation with changes in depressive symptoms 3 months after ACS, (2) to prospectively assess whether rumination interacts with other vulnerabilities as a predictor of later depressive symptoms, and (3) to examine how these relations differ between post-ACS patients who meet diagnostic criteria for depression at baseline versus patients who do not. Within 1 week after hospitalization for ACS, and again after 3 months, 387 patients (41% female, 79.6% white, mean age 61) completed the Beck Depression Inventory (BDI) and measures of vulnerabilities (lack of pleasant events, dysfunctional attitudes, role transitions, poor dyadic adjustment). Exclusion criteria were a BDI score of 5–9, terminal illness, active substance abuse, cognitive impairment, and unavailability for follow-up visits. We used hierarchical regression modeling cross-sectionally and longitudinally. Controlling for baseline (in-hospital) depression and cardiovascular disease severity, vulnerabilities significantly predicted 3 month depression severity. Rumination independently predicted increased depression severity, above other vulnerabilities (β = 0.75, p < 0.001), and also interacted with poor dyadic adjustment (β = 0.32, p < 0.001) to amplify depression severity. Among initially non-depressed patients, the effects of vulnerabilities were amplified by rumination. In contrast, in patients who were already depressed at baseline, there was a direct effect of rumination above vulnerabilities on depression severity. Although all vulnerabilities predict depression 3 months after an ACS event has occurred rumination plays a key role to amplify the impact of vulnerabilities on depression among the initially non-depressed, and maintains depression among those who are already depressed.

Posttraumatic stress disorder (PTSD) is related to acute coronary syndrome (ACS; i.e., myocardial infarction or unstable angina) recurrence and poor post-ACS adherence to medical advice. Since risk perceptions are a primary motivator of adherence behaviors, we assessed the relationship of probable PTSD to ACS risk perceptions in hospitalized ACS patients (n = 420). Participants completed a brief PTSD screen 3–7 days post-ACS, and rated their 1-year ACS recurrence risk relative to other men or women their age. Most participants exhibited optimistic bias (mean recurrence risk estimate between “average” and “below average”). Further, participants who screened positive for current PTSD (n = 15) showed significantly greater optimistic bias than those who screened negative (p

The affiliation for the twentieth author was incorrect. Mary Carrington is not affiliated with #10 but with #12 Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland, United States of America. The author’s affiliation to #18 is unaffected.

According to the linear theory of elasticity, there exists a combination of different orders of stress singularity at a V-notch tip of bonded dissimilar materials. The singularity reflects a strong stress concentration near the sharp V-notches. In this paper, a new way is proposed\ud in order to determine the orders of singularity for two-dimensional V-notch problems. Firstly, on the basis of an asymptotic stress field in terms of radial coordinates at the V-notch tip, the governing equations of the elastic theory are transformed into an eigenvalue problem of ordinary differential equations (ODEs) with respect to the circumferential coordinate h around the notch tip. Then the interpolating matrix method established by the first author is further developed to solve the general eigenvalue problem. Hence, the singularity orders of the V-notch problem are determined through solving the corresponding\ud ODEs by means of the interpolating matrix method. Meanwhile, the associated eigenvectors of the displacement and stress fields near the V-notches are also obtained. These functions are essential in calculating the amplitude of the stress field described as generalized stress intensity factors of the V-notches. The present method is also available to deal with the plane V-notch problems in bonded orthotropic multi-material. Finally, numerical\ud examples are presented to illustrate the accuracy and the effectiveness of the method.\ud

Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the ĝ€ genomic disordersĝ€™, have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition. © 2009 Macmillan Publishers Limited., link_to_OA_fulltext

Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia. ©2008 Macmillan Publishers Limited. All rights reserved., link_to_OA_fulltext

Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia.

Neural stem cells (NSCs) with the capacity of extensive self-renewal and multilineage differentiation have attracted more and more attention in research as NSCs will play an important role in the nerve disease treatment and nerve injury repair. The shortage of NSCs, both their sources and their numbers, however, is the biggest challenge for their clinic application, and hence, in vitro culture and expansion of NSCs is vitally important to realize their potentials. In this work, mouse-derived NSCs were cultured in three-dimensional calcium alginate beads (Ca-Alg-Bs). Gelling conditions, cell density, and cell harvest were determined by the exploration of formation and dissociation parameters for Ca-Alg-Bs. Additionally, the recovered and the subsequent induced cells were identified by immunofluorescence staining of Nestin, beta-tubulin, and GFAP. The results show that the 2-mm diameter Ca-Alg-Bs, prepared with 1.5% sodium alginate solution and 3.5% CaCl2 solution and with gelling for 10 min, is suitable for the NSCs culture. The seeding density of 0.8 x 10(5) cells x mL-1 for the encapsulation of NSCs resulted in the most expansion, and the NSCs almost doubled during the experiment. The average cell recovery rate is over 88.5%, with the Ca-Alg-Bs dissolving in 55 mM sodium citrate solution for 10 min. The recovered cells cultured in the Ca-Alg-Bs still expressed Nestin and had the capacity of multilineage differentiation into neurons and glial cells and, thus, remained to be NSCs. These results demonstrate that NSC expansion within Ca-Alg-Bs is feasible and provides further possibilities for NSC expansion in bioreactors of the scale of clinical relevance.

The osteoblasts were expanded in large-scale by microcarrier suspension culture in rotating wall vessel bioreactor (RWV), then the biological functions of the cells were detected by histomorphometry and the cells were seeded at 2 × 106 cells/ml and 1 × 106 cells/ml onto scaffolds respectively to culture for 2 weeks. The biological properties of the fabricated bone tissue were detected by inverted microscope, scanning electron microscope (SEM), alkaline phosphatase (ALP), von-Kossa staining on mineralized nodules and AO/EB fluorescence staining. Meanwhile the cells' metabolism of nutrients was monitored and analyzed during the whole culture process. The bone tissue fabricated in RWV with two different seeded cell densities grew well. Osteoblasts in the scaffolds secreted much collagen fibers and formed mineralized nodules and new osteoid tissue. It can be conclueled that : With the stress stimulation inside the fluid in the RWV, the active expression of ALP can be increased, the formation of mineralized nodules can be accelerated. The rapid proliferation and differentiation of osteoblasts are possible and the three-dimensional fabrication ol engineered bone could be realized.