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Jia-Wen Zhang,1,2 Mao-Min Jiang,3 Shi-Ying Yang4 1School of Education, Silliman University, Dumaguete, 6200, Philippines; 2Xiamen Institute of Software Technology, Xiamen, Fujian, People’s Republic of China; 3School of Public Affairs, Xiamen University, Xiamen, 361005, People’s Republic of China; 4Lanwanyihe School, Xiamen, 361100, People’s Republic of ChinaCorrespondence: Shi-Ying Yang, Email yangshiying012@163.comObjective: To explore the influence of bully victims on the suicidal tendencies of college students, and the moderating role of teacher emotional support and family support in the relationship between bully victims and college students’ suicidal tendencies, in order to provide a reference for the effective intervention of college students’ suicide behavior.Methods: Based on a survey of 15,560 college students. Multiple stepwise regression and Interaction analysis explore the impact of the bully victimization on college students’ suicidal tendencies and the moderating role of family support and teacher emotional support in the relationship between the bully victim and college students’ suicidal tendencies.Results: This study found that the Suicidal Tendencies score of college students was 19.79 points, indicating that some college students have a risk of suicidal tendencies; secondly, verbal bullying (β = 0.084, P < 0.001), physical bullying (β = 0.222, P < 0.001) and social relationship bullying (β = 0.122, P < 0.001) have a positive and significant impact on the suicidal tendencies of college students; in addition, family support and teacher emotional support have a significant regulatory effect on the bully victim and college students Suicidal Tendencies and family support. The regulating effect was significantly higher than that of teacher emotional support.Conclusion: Chinese college students have the risk of suicidal tendencies; peer bullying victimization is an important reason for affecting college students’ suicidal tendencies, teacher emotional support is a protective factor for bully victims to affect college students’ suicidal tendencies, and family support has a significant moderating effect on the bully victim and college students’ suicidal tendencies. Therefore, it is necessary to actively adopt home-school linkage and home-school communication to reduce campus violence and increase the psychological resilience of college students.Keywords: bully victim, teachers’ emotional support, family support, suicidal tendencies, college students

Mitochondrial DNA copy number (mtDNA-CN) measured from blood specimens is a minimally invasive marker of mitochondrial function that exhibits both inter-individual and intercellular variation. To identify genes involved in regulating mitochondrial function, we performed a genome-wide association study (GWAS) in 465,809 White individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (UKB). We identified 133 SNPs with statistically significant, independent effects associated with mtDNA-CN across 100 loci. A combination of fine-mapping, variant annotation, and co-localization analyses was used to prioritize genes within each of the 133 independent sites. Putative causal genes were enriched for known mitochondrial DNA depletion syndromes (p = 3.09 × 10-15) and the gene ontology (GO) terms for mtDNA metabolism (p = 1.43 × 10-8) and mtDNA replication (p = 1.2 × 10-7). A clustering approach leveraged pleiotropy between mtDNA-CN associated SNPs and 41 mtDNA-CN associated phenotypes to identify functional domains, revealing three distinct groups, including platelet activation, megakaryocyte proliferation, and mtDNA metabolism. Finally, using mitochondrial SNPs, we establish causal relationships between mitochondrial function and a variety of blood cell-related traits, kidney function, liver function and overall (p = 0.044) and non-cancer mortality (p = 6.56 × 10-4).

Hyung Cheol Kim,1,&ast; Min Cheol Chang,2,&ast; Sung Han Oh,1 Su Bin Lee,3 Soo Young Yang,3 Dong Ah Shin3 1Department of Neurosurgery, Bundang Jesaeng General Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea; 2Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University, Namku, Taegu, Republic of Korea; 3Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Dong Ah Shin, Department of Neurosurgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemungu, Seoul, 03722, Republic of Korea, Tel +82 02-2-2228-1004, Email cistern@yuhs.acPurpose: This study aimed to use thermal grill illusion (TGI), an experimental model of pain processing and central mechanisms, to evaluate the perception of TGI-related sensations or pain in patients with chronic lower back pain (CLBP).Patients and Methods: The perception of TGI (warmth/heat, cold, unpleasantness, pain, burning, stinging, and prickling) was examined in 66 patients with CLBP and compared with that in 22 healthy participants. The visual analog scale (VAS) scores for CLBP, Oswestry Disability Index (ODI), and 12-Item Short Form Survey (SF-12) scores were obtained from the included patients with CLBP.Results: The CLBP group showed a less intense perception of TGI for sensations of warmth/heat, unpleasantness, and pain than the control group. The CLBP group felt burning sensations lesser than the control (2.77 vs 4.55, P=0.016). In the CLBP group, there were significant correlations between the ODI and the degree of unpleasantness (r=0.381, P=0.002) and prickling sensation (r=0.263, P=0.033). There were also significant correlations between the mental component score of the SF-12 and the degree of warmth/heat (r=− 0.246, P=0.046), unpleasantness (r=− 0.292, P=0.017), pain (r=− 0.292, P=0.017), and burning sensations (r=− 0.280, P=0.023).Conclusion: Our results may be useful for clinicians to evaluate the effectiveness of drugs or interventions to manage centralized LBP.Keywords: thermal grill illusion, chronic pain, back pain

Multiferroic BiFeO3 (BFO) shows several phonon modes at infrared (IR) to THz energies, which are expected to carry information on any sample property coupled to crystal lattice vibrations. While macroscopic IR studies of BFO are often limited by single-crystal size, scattering-type scanning near-field optical microscopy (s-SNOM) allows for IR thin film spectroscopy of nanoscopic probing volumes with negligible direct substrate contribution to the optical signal. In fact, polaritons such as phonon polaritons of BFO introduce a resonant tip-sample coupling in s-SNOM, leading to both stronger signals and enhanced sensitivity to local material properties. Here, we explore the near-field response of BFO thin films at three consecutive resonances (centered around 5 THz, 13 THz, and 16 THz), by combining s-SNOM with a free-electron laser. We study the dependence of these near-field resonances on both the wavelength and tip-sample distance. Enabled by the broad spectral range of the measurement, we probe phonon modes connected to the predominant motion of either the bismuth or oxygen ions. Therefore, we propose s-SNOM at multiple near-field resonances as a versatile and very sensitive tool for the simultaneous investigation of various sample properties.

Zhaoyang Guo,1,&ast; Yuanye Ma,1,&ast; Yaqing Wang,2 Hongfei Xiang,1 Shang-You Yang,3 Zhu Guo,1 Ronghuan Wang,1 Wujun Chen,4 Dongming Xing,4,5 Bohua Chen,1 Hao Tao,1 Xiaolin Wu1,4 1Department of Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Nephrology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 3School of Medicine-Wichita, University of Kansas, Wichita, KS, USA; 4Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, People’s Republic of China; 5School of Life Sciences, Tsinghua University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaolin Wu; Hao Tao, Department of Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Email fyqs01@qdu.edu.cn; taohaob2008@163.comBackground: It is well established that discogenic low back pain (DLBP) is often caused by the inflammatory response during intervertebral disc degeneration (IDD). However, it remains unclear how inflammatory mediators such as Interleukin-6 (IL-6) are involved in discogenic pain caused by degeneration and intervertebral disc (IVD) metabolism. The purpose of this study is to study the relationship between IL-6 and Transmembrane protein 100 (TMEM100), and to analyze the different metabolites and metabolic pathways in various rat intervertebral discs by metabonomics.Methods: We established a rat model of IDD-DLBP by disc punctures and PBS infusion to examine the rat pain behaviors. Intervertebral disc tissues were harvested for molecular biology experiments to explore the relationship between IL-6 and TMEM100. High-resolution mass spectrometry (HRMS) was performed for untargeted metabolomics, and nuclear magnetic resonance spectroscopy metabolomics (MRS) for differential metabolites and metabolic pathways.Results: The results showed a significant decrease in vonFrey test, hot plate test and acetone test (P < 0.05). The expression of IL-6 and TMEM100 in DLBP model was significantly higher than that in sham control group and IDD discs without PBS infusion group (P < 0.05). There were 15 major contributing metabolites identified in the DLBP intervertebral discs through metabolomic studies, involving 6 major metabolic pathways. The main differential metabolites included nitric oxide (NO), ammonia, and lactic acid as the metabolic endpoints; and the differential metabolic pathways included the glycine-serine-threonine (Gly-Ser-Thr), which is gradually weakened with the progression of inflammation.Conclusion: The change of TMEM100 expression mediated by il-6 is related to the Gly-Ser-Thr metabolic axis and plays an important role in the relief of discogenic pain.Keywords: metabolomics, DLBP, IDD, IL-6, TMEM100, inflammatory mediators

Wen-Guang Zhang,1 Jia-Wei Liu,2 Su-Yun Yang,3 Qiao-Qian Wang,4 Chen-Xing Liu,2 Yao Li2 1Department of Nursing, The First Hospital of Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 2School of Nursing, Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 3Department of Nuclear Medicine, The First Hospital of Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 4Department of Hypertension, The First Hospital of Shanxi Medical University, Taiyuan, 030000, People’s Republic of ChinaCorrespondence: Su-Yun YangDepartment of Nuclear Medicine, The First Hospital of Shanxi Medical University, Room 601, Unit 8, Building 1, No. 8 Wenyuan Lane, Yingze District, Taiyuan, 030000, People’s Republic of ChinaTel +8613603512029Email syy_dr09sun@163.comObjective: This study aimed to evaluate the effect of closed-loop management on nursing disruption risk.Methods: Using a quasi-experimental research method, convenient sampling was used to extract 20 nurses working at our hospital as the research objects. The control group members were selected from January to March 2018 via the traditional method, and the experimental group members were selected from April to June 2018 via the closed-loop management method. At three months before and after the implementation of the management model, a self-designed quantitative test form and satisfaction questionnaire were used to analyze the frequency of nursing disruption events, the accuracy rate of doctors’ advice, the average drug delivery time of the static distribution center, the implementation rate of personal digital assistant (PDA) code scanning, and the report rate of risk-outcome nursing disruption events.Results: After the implementation of the management model, the frequency of nursing disruptions and average drug delivery time of the static distribution center were significantly lower than before, and the differences were statistically significant (p < 0.05). Moreover, the accuracy rate of doctors’ advice, the implementation rate of PDA code scanning, and the reporting rate of risk-outcome nursing disruption events were significantly higher than before, and these differences were statistically significant as well (p < 0.05).Conclusion: The application of a closed-loop management model could significantly reduce the occurrence and optimize the outcomes of nursing disruption events and improve the work processes of medical care.Keywords: closed-loop management, nursing interruption, risk control, personal digital assistant, PDA, management mode

Antitumor T cells are subject to multiple mechanisms of negative regulation. Recent findings that innate lymphoid cells (ILCs) regulate adaptive T cell responses led us to examine the regulatory potential of ILCs in the context of cancer. We identified a unique ILC population that inhibits tumor-infiltrating lymphocytes (TILs) from high-grade serous tumors, defined their suppressive capacity in vitro, and performed a comprehensive analysis of their phenotype. Notably, the presence of this CD56+CD3- population in TIL cultures was associated with reduced T cell numbers, and further functional studies demonstrated that this population suppressed TIL expansion and altered TIL cytokine production. Transcriptome analysis and phenotypic characterization determined that regulatory CD56+CD3- cells exhibit low cytotoxic activity, produce IL-22, and have an expression profile that overlaps with those of natural killer (NK) cells and other ILCs. NKp46 was highly expressed by these cells, and addition of anti-NKp46 antibodies to TIL cultures abrogated the ability of these regulatory ILCs to suppress T cell expansion. Notably, the presence of these regulatory ILCs in TIL cultures corresponded with a striking reduction in the time to disease recurrence. These studies demonstrate that a previously uncharacterized ILC population regulates the activity and expansion of tumor-associated T cells.

Yi-Jing Chen,1,2 Jing Chang,1 Si-Yu Yang3 1Department of Health Care Clinic, First Affiliated Hospital of Zhengzhou University, Henan, People’s Republic of China; 2Academy of Medical Science, Zhengzhou University, Henan, People’s Republic of China; 3Xiangya Medical School, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Jing Chang Email jingchang101@163.comObjective: This study aimed to develop the ARMS-C and test its psychometric properties in hypertensive patients, to assess the level of medication adherence and to identify associated predictors for medication adherence and blood-pressure control among Chinese hypertensive patients.Methods: Hypertensive elderly who met inclusion criteria were recruited from an aged-care facility in Henan Province between January 2019 and July 2019. The patients completed the adapted ARMS-C. The scale’s factor structure, internal consistency, and construct validity were tested.Results: Good internal consistency (Cronbach’s α=0.89) and test–retest reliability (r=0.86, p< 0.01) were obtained. Item-total correlation coefficients for the ten-item ARMS-C were 0.505– 0.801. Factor analysis of construct validity identified two factors, explaining a total variance of 63.3%. Binary regression showed that patients with scores at level 2 (≤ 20 ARMS-10 scores < 30) were six times as likely to have blood pressure uncontrolled as those at level 1 (ARMS-10 scores < 20, OR 6.6, 95% CI 1.7– 25.1; p=0.006), and patients with scores at level 3 (ARMS-10 scores > 30) were 115 times as likely to have blood pressure uncontrolled as those at level 1 (ARMS-10 scores < 20,OR 115, 95% CI 9– 1,470; p=0).Conclusion: The ten-item ARMS-C is a reliable and valid self-reporting screening tool for adherence to medication and refills in elderly hypertensive Chinese patients.Keywords: adherence, 10-item ARMS, hypertension, blood-pressure control

The control of material interfaces at the atomic level has led to novel interfacial properties and functionalities. In particular, the study of polar discontinuities at interfaces between complex oxides lies at the frontier of modern condensed matter research. Here we employ a combination of experimental measurements and theoretical calculations to demonstrate the control of a bulk property, namely ferroelectric polarization, of a heteroepitaxial bilayer by precise atomic-scale interface engineering. More specifically, the control is achieved by exploiting the interfacial valence mismatch to influence the electrostatic potential step across the interface, which manifests itself as the biased-voltage in ferroelectric hysteresis loops and determines the ferroelectric state. A broad study of diverse systems comprising different ferroelectrics and conducting perovskite underlayers extends the generality of this phenomenon.

Piezoelectric materials exhibit a mechanical response to electrical inputs, as well as an electrical response to mechanical inputs, which makes them useful in sensors and actuators. Lead-based piezoelectrics demonstrate a large mechanical response, but they also pose a health risk. The ferroelectric BiFeO(3) is an attractive alternative because it is lead-free, and because strain can stabilize BiFeO(3) phases with a structure that resembles a morphotropic phase boundary. Here we report a reversible electric-field-induced strain of over 5% in BiFeO(3) films, together with a characterization of the origins of this effect. In situ transmission electron microscopy coupled with nanoscale electrical and mechanical probing shows that large strains result from moving the boundaries between tetragonal- and rhombohedral-like phases, which changes the phase stability of the mixture. These results demonstrate the potential of BiFeO(3) as a substitute for lead-based materials in future piezoelectric applications.

Xinpei Zhang,1 Jinlong Shi,2 Jilei Zhang,1 Xinrui Yang,1 Gaoqi Zhang,1 Siyuan Yang,1 Jing Wang,1 Xiaoyan Ke,1 Lin Fu1 1Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing 100191, China; 2Department of Biomedical Engineering, Chinese PLA General Hospital, Beijing 100853, China Purpose: The incidence of DNMT3A mutations in acute myeloid leukemia (AML) is quite high and often confers a poorer prognosis. Another common gene involved in AML is IDH1/2. However, the influence of IDH1/2 mutations on outcomes in DNMT3A-mutated patients remains unknown. This study aims to determine the effect of IDH1/2mut on the prognosis in patients with DNMT3A-mutated AML. Patients and methods: We screened patients from The Cancer Genome Atlas database and selected 51 patients with AML and the DNMT3A mutation, among which 16 patients (31.4%) had both DNMT3A and IDH1/2mut. Results: Among our sample, 11 cases had the IDH1 mutation (21.7%), and 5 cases had the IDH2 mutation (9.8%). Patients in the DNMT3AmutIDH1/2wild group showed a greater number of NPM1 mutation (P=0.022), and higher event-free survival (EFS) and overall survival (OS) after hematopoietic stem cell transplantation (HSCT) (P=0.010 and P=0.007, respectively). Patients in the DNMT3AmutIDH1/2mut group showed no increase in EFS or OS after HSCT or chemotherapy. Other factors, like white blood cells, bone marrow blasts, peripheral blood blasts, and mutated recurrent gene numbers had no significant influence on EFS and OS. Conclusion: The IDH1/2 gene had little influence on the prognosis of patients with the DNMT3A mutation. For patients in the DNMT3AmutIDH1/2wild group, HSCT had a more favorable therapeutic effect. For patients with DNMT3A and IDH1/2mut, chemotherapy and HSCT appeared to have similar efficacy. Keywords: acute myeloid leukemia, molecular mutations, prognosis, next-generation sequencing

We report the formation of a novel ferromagnetic state in the antiferromagnet BiFeO3 at the interface with ferromagnet La(0.7)Sr(0.3)MnO3. Using x-ray magnetic circular dichroism at Mn and Fe L(2,3) edges, we discovered that the development of this ferromagnetic spin structure is strongly associated with the onset of a significant exchange bias. Our results demonstrate that the magnetic state is directly related to an electronic orbital reconstruction at the interface, which is supported by the linearly polarized x-ray absorption measurement at the oxygen K edge.

In conventional solid-state photovoltaics, electron-hole pairs are created by light absorption in a semiconductor and separated by the electric field spaning a micrometre-thick depletion region. The maximum voltage these devices can produce is equal to the semiconductor electronic bandgap. Here, we report the discovery of a fundamentally different mechanism for photovoltaic charge separation, which operates over a distance of 1-2 nm and produces voltages that are significantly higher than the bandgap. The separation happens at previously unobserved nanoscale steps of the electrostatic potential that naturally occur at ferroelectric domain walls in the complex oxide BiFeO(3). Electric-field control over domain structure allows the photovoltaic effect to be reversed in polarity or turned off. This new degree of control, and the high voltages produced, may find application in optoelectronic devices.

Xue Bai,1 Shuyan Yang,2 Martin Knapp3 1Department of Applied Social Sciences, The Hong Kong Polytechnic University, Hong Kong, People’s Republic of China; 2Department of Social Work, Hong Kong Baptist University, Hong Kong, People’s Republic of China; 3Personal Social Services Research Unit, London School of Economics and Political Science, London, UK Abstract: Based on survey data collected from 151 community-dwelling solitary Chinese older adults in Hong Kong, the present study used path analysis to examine the mediating role of sense of loneliness in the relationship between different sources and directions of social support and life satisfaction. The results showed that sense of loneliness mediated the effects of support from families, friends, and support for others on life satisfaction. In addition, a formal source of social support was not associated with life satisfaction among solitary older adults, although those with a more secure financial status had greater overall life satisfaction. These findings highlight the importance of enhancing awareness among social and health care service providers about the negative effects of insufficient social support on older adults’ sense of loneliness and life satisfaction. Family and friendship networks should be expanded for solitary older adults. Keywords: life satisfaction, path analysis, solitary older adults, sense of loneliness, social support

We report a photovoltaic effect in ferroelectric BiFeO3 thin films. The all-oxide heterostructures with SrRuO3 bottom and tin doped indium oxide top electrodes are characterized by open-circuit voltages ∼0.8-0.9 V and external quantum efficiencies up to ∼10% when illuminated with the appropriate light. Efficiencies are at least an order of magnitude larger than the maximum efficiency under sunlight (AM 1.5) thus far reported for ferroelectric-based devices. The dependence of the measured open-circuit voltage on film thickness suggests contributions to the large open-circuit voltage from both the ferroelectric polarization and band offsets at the BiFeO3 /tin doped indium oxide interface. © 2009 American Institute of Physics.

Sarwat B Rizvi,1 Sepideh Rouhi,1 Shohei Taniguchi,2 Shi Yu Yang,1 Mark Green,2 Mo Keshtgar,1,3 Alexander M Seifalian1,3 1UCL Centre for Nanotechnology and Regenerative Medicine, University College London, 2Department of Physics, King's College London, 3Royal Free London NHS Foundation Trust Hospital, London, UK Background: Quantum dots are fluorescent nanoparticles with unique photophysical properties that allow them to be used as diagnostic, therapeutic, and theranostic agents, particularly in medical and surgical oncology. Near-infrared-emitting quantum dots can be visualized in deep tissues because the biological window is transparent to these wavelengths. Their small sizes and free surface reactive groups that can be conjugated to biomolecules make them ideal probes for in vivo cancer localization, targeted chemotherapy, and image-guided cancer surgery. The human epidermal growth factor receptor 2 gene (HER2/neu) is overexpressed in 25%–30% of breast cancers. The current methods of detection for HER2 status, including immunohistochemistry and fluorescence in situ hybridization, are used ex vivo and cannot be used in vivo. In this paper, we demonstrate the application of near-infrared-emitting quantum dots for HER2 localization in fixed and live cancer cells as a first step prior to their in vivo application. Methods: Near-infrared-emitting quantum dots were characterized and their in vitro toxicity was established using three cancer cell lines, ie, HepG2, SK-BR-3 (HER2-overexpressing), and MCF7 (HER2-underexpressing). Mouse antihuman anti-HER2 monoclonal antibody was conjugated to the near-infrared-emitting quantum dots. Results: In vitro toxicity studies showed biocompatibility of SK-BR-3 and MCF7 cell lines with near-infrared-emitting quantum dots at a concentration of 60 µg/mL after one hour and 24 hours of exposure. Near-infrared-emitting quantum dot antiHER2-antibody bioconjugates successfully localized HER2 receptors on SK-BR-3 cells. Conclusion: Near-infrared-emitting quantum dot bioconjugates can be used for rapid localization of HER2 receptors and can potentially be used for targeted therapy as well as image-guided surgery. Keywords: anti-HER2 antibody, HER2 localization, quantum dots, in vitro imaging, nanotechnology, cancer

Mei Xue, Ming-xing Yang, Wei Zhang, Xiu-min Li, De-hong Gao, Zhi-min Ou, Zhi-peng Li, Su-huan Liu, Xue-jun Li, Shu-yu Yang Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China Abstract: The high aqueous solubility, poor permeability, and absorption of berberine (BBR) result in its low plasma level after oral administration, which greatly limits its clinical application. BBR solid lipid nanoparticles (SLNs) were prepared to achieve improved bioavailability and prolonged effect. Developed SLNs showed homogeneous spherical shapes, small size (76.8 nm), zeta potential (7.87 mV), encapsulation efficiency (58%), and drug loading (4.2%). The power of X-ray diffraction combined with 1H nuclear magnetic resonance spectroscopy was employed to analyze chemical functional groups and the microstructure of BBR-SLNs, and indicated that the drug was wrapped in a lipid carrier. Single dose (50 mg/kg) oral pharmacokinetic studies in rats showed significant improvement (P

Nianhu Li,1,2,* Zhanwang Xu,2,* Paul H Wooley,1,3 Jianxin Zhang,2 Shang-You Yang1,3 1Department of Surgery, Orthopedics, University of Kansas School of Medicine, Wichita, KS, USA; 2Department of Orthopedics, Affiliated Hospital to Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China; 3Orthopaedic Research Institute, Via Christi Wichita Hospitals, Wichita, KS, USA *The first two authors contributed equally to this work Abstract: Wear debris associated periprosthetic osteolysis represents a major pathological process associated with the aseptic loosening of joint prostheses. Naringin is a major flavonoid identified in grapefruit. Studies have shown that naringin possesses many pharmacological properties including effects on bone metabolism. The current study evaluated the influence of naringin on wear debris induced osteoclastic bone resorption both in vitro and in vivo. The osteoclast precursor cell line RAW 264.7 was cultured and stimulated with polymethylmethacrylate (PMMA) particles followed by treatment with naringin at several doses. Tartrate resistant acid phosphatase (TRAP), calcium release, and gene expression profiles of TRAP, cathepsin K, and receptor activator of nuclear factor-kappa B were sequentially evaluated. PMMA challenged murine air pouch and the load bearing tibia titanium pin-implantation mouse models were used to evaluate the effects of naringin in controlling PMMA induced bone resorption. Histological analyses and biomechanical pullout tests were performed following the animal experimentation. The in vitro data clearly demonstrated the inhibitory effects of naringin in PMMA induced osteoclastogenesis. The naringin dose of 10 µg/mL exhibited the most significant influence on the suppression of TRAP activities. Naringin treatment also markedly decreased calcium release in the stimulated cell culture medium. The short-term air pouch mouse study revealed that local injection of naringin ameliorated the PMMA induced inflammatory tissue response and subsequent bone resorption. The long-term tibia pin-implantation mouse model study suggested that daily oral gavage of naringin at 300 mg/kg dosage for 30 days significantly alleviated the periprosthetic bone resorption. A significant increase of periprosthetic bone volume and regaining of the pin stability were found in naringin treated mice. Overall, this study suggests that naringin may serve as a potential therapeutic agent to treat wear debris associated osteolysis. Keywords: naringin, osteoclastogenesis, aseptic loosening, periprosthetic osteolysis

Chien-Hsi Chang,1 Zhi-Xian Lai,1 Hsiu-Li Lin,2 Che-Chuan Yang,3 Hsin-Hsien Chen,3,4 Shieh-Yueh Yang,5 Herng-Er Horng,3 Chin-Yih Hong,6 Hong-Chang Yang,4 Hsiu-Chen Lin1,71Department of Laboratory Medicine, Taipei Medical University Hospital, 2Department of Neurology, General Cathay Hospital, Sijhih Branch, 3Institute of Electro-optical Science and Technology, National Taiwan Normal University, 4Department of Physics, National Taiwan University, 5MagQu Co, Ltd, Sindian District, New Taipei City, 6Department of Mechanical Engineering, Nan-Kai University of Technology, Nan-tau County, 7Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, TaiwanBackground: Magnetic nanoparticles biofunctionalized with antibodies are able to recognize and bind to the corresponding antigens. In this work, anti-C-reactive protein (CRP) antibody was covalently conjugated onto the surface of magnetic nanoparticles to label CRP specifically in serum.Methods: The level of serum CRP was detected by immunomagnetic reduction (IMR) assay, which identifies the changes in the magnetic signal representing the level of interaction between antibody-conjugated magnetic nanoparticles and CRP proteins. To investigate the feasibility of IMR for clinical application, pure CRP solutions and 40 human serum samples were tested for IMR detection of CRP to characterize sensitivity, specificity, and interference.Results: In comparison with the immunoturbidimetry assay, the results of the IMR assay indicated higher sensitivity and had a high correlation with those of the current immunoturbidimetry assay.Conclusion: We have developed a novel and promising way to assay CRP in human serum using immunomagnetic reduction in clinical diagnosis.Keywords: magnetic nanoparticles, immunomagnetic reduction, C-reactive protein

Wan-Ju Hsieh,1 Chan-Jung Liang,1 Jen-Jie Chieh,4 Shu-Huei Wang,1 I-Rue Lai,1 Jyh-Horng Chen,2 Fu-Hsiung Chang,3 Wei-Kung Tseng,4–6 Shieh-Yueh Yang,4 Chau-Chung Wu,7 Yuh-Lien Chen11Institute of Anatomy and Cell Biology, College of Medicine, 2Department of Electrical Engineering, 3Institute of Biochemistry and Molecular Biology, National Taiwan University, Taipei, Taiwan; 4Institute of Electro-Optical Science and Technology, National Taiwan Normal University, Taipei, Taiwan; 5Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Taipei, Taiwan; 6Department of Medical Imaging and Radiological Sciences, I-Shou University, Taipei, Taiwan; 7Department of Internal Medicine and Primary Care Medicine, National Taiwan University Hospital, Taipei, TaiwanBackground: Active targeting by specific antibodies combined with nanoparticles is a promising technology for cancer imaging and detection by magnetic resonance imaging (MRI). The aim of the present study is to investigate whether the systemic delivery of antivascular endothelial growth factor antibodies conjugating to the surface of functionalized supermagnetic iron oxide nanoparticles (anti-VEGF-NPs) led to target-specific accumulation in the tumor.Methods: The VEGF expression in human colon cancer and in Balb/c mice bearing colon cancers was examined by immunohistochemistry. The distribution of these anti-VEGF-NPs particles or NPs particles were evaluated by MRI at days 1, 2, or 9 after the injection into the jugular vein of Balb/c mice bearing colon cancers. Tumor and normal tissues (liver, spleen, lung, and kidney) were collected and were examined by Prussian blue staining to determine the presence and distribution of NPs in the tissue sections.Results: VEGF is highly expressed in human and mouse colon cancer tissues. MRI showed significant changes in the T*2 signal and T2 relaxation in the anti-VEGF-NP- injected-mice, but not in mice injected with NP alone. Examination of paraffin sections of tumor tissues stained for the iron constituent of the NPs with Prussian blue revealed a strong blue reaction in the tumors of anti-VEGF-NP-treated mice, but only a weak reaction in mice injected with NPs. In both groups, at all time points, Prussian blue-stained liver and spleen sections showed only light staining, while stained cells were rarely detected in kidney and lung sections. Transmission electron microscopy showed that many more electron-dense particles were present in endothelial cells, tumor cells, and extracellular matrix in tumor tissues in mice injected with anti-VEGF-NPs than in NP-injected mice.Conclusion: These results demonstrated in vivo tumor targeting and efficient accumulation of anti-VEGF-NPs in tumor tissues after systemic delivery in a colon cancer model, showing that anti-VEGF-NPs have potential for use as a molecular-targeted tumor imaging agent in vivo.Keywords: nanoparticles, vascular endothelial growth factor, colon tumor, magnetic resonance imaging, transmission electron microscopy

Kai-Wen Huang1, Shieh-Yueh Yang2,3, Yu-Wei Hong3, Jen-Jie Chieh3, Che-Chuan Yang3, Herng-Er Horng3, Chau-Chung Wu4, Chin-Yih Hong5, Hong-Chang Yang61Department of Surgery and Hepatitis Research Center, National Taiwan University Hospital, National Taiwan University, Taipei, 2MagQu Co, Ltd, Sindian Dist, New Taipei City, 3Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei, 4Departments of Internal Medicine and Primary Care Medicine, College of Medicine, National Taiwan University, Taipei, 5Graduate Institute of Bio-medical Engineering, National Chung Hsing University, Taichung, 6Department of Physics, National Taiwan University, Taipei, TaiwanAbstract: Some previous reports have already shown the characterizations of immunomagnetic reduction (IMR). The assay technology involves the utilities of biofunctionalized magnetic nanoparticles to label target biomolecules. However, the detection threshold and interference tests for IMR have not been investigated in detail. In this study, alpha-fetoprotein (AFP) was used as a target biomolecule. The signals for AFP solutions of various concentrations, or with interfering materials, were detected via IMR. These samples were also used for characterizing the detection threshold and interference with enzyme-linked immunosorbent assay (ELISA). The results of assaying AFP level with IMR and ELISA were compared. The detection threshold for assaying AFP with IMR was found to be 3 ng/mL, which is 15 times lower than that of ELISA, and definitely suppresses false negative. For the interfering materials noted commonly in serum such as hemoglobin, bilirubin, triglyceride, and vascular endothelial growth factor, there was no detectable interfering effect when assaying AFP with IMR. Several serum samples from normal people and liver-tumor-bearing patients were used for the detections of AFP concentration via IMR. These results reveal the feasibilities of assaying AFP in blood using IMR, as well as achieving high-sensitive and high-specific assay for AFP.Keywords: immunomagnetic reduction, ELISA, biofunctionalized magnetic nanoparticles

Abstract X-ray photoelectron spectroscopy has been used to measure the valence band offset (VBO) of the w-InN/h-BN heterojunction. We find that it is a type-II heterojunction with the VBO being −0.30 ± 0.09 eV and the corresponding conduction band offset (CBO) being 4.99 ± 0.09 eV. The accurate determination of VBO and CBO is important for designing the w-InN/h-BN-based electronic devices.

Abstract Diamond is not only a free standing highly transparent window but also a promising carrier confinement layer for InN based devices, yet little is known of the band offsets in InN/diamond system. X-ray photoelectron spectroscopy was used to measure the energy discontinuity in the valence band offset (VBO) of InN/diamond heterostructure. The value of VBO was determined to be 0.39 ± 0.08 eV and a type-I heterojunction with a conduction band offset (CBO) of 4.42 ± 0.08 eV was obtained. The accurate determination of VBO and CBO is important for the application of III-N alloys based electronic devices.