Suchergebnisse

Ba Hieu Tran,1–3 Ying Yu,1,4 Lingling Chang,1 Bo Tan,5 Wanwan Jia,1 Ying Xiong,1 Tao Dai,1 Rui Zhong,1 Weiping Zhang,6 Van Minh Le,7 Peter Rose,8 Zhijun Wang,1,2 Yicheng Mao,1,* Yi Zhun Zhu1,2,* 1School of Pharmacy, Fudan University, Shanghai, People's Republic of China; 2School of Pharmacy, Macau University of Science and Technology, Taipa, Macau; 3Institute of Biomedicine and Pharmacy, Vietnam Military Medical University, Hanoi, Vietnam; 4Department of Cardiology, Xinhua Hospital, Shanghai, People's Republic of China; 5Department of Clinical Pharmacology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China; 6Department of Hematology, Institute of Hematology of PLA, Changhai Hospital, Shanghai, People's Republic of China; 7NTT Institute of Hi-Technology (NIH), Nguyen Tat Thanh University, Ho Chi Minh City, Viet Nam; 8School of Biosciences, University of Nottingham, Loughborough, LE12 5RD, UK*These authors contributed equally to this workCorrespondence: Yicheng Mao; Yi Zhun ZhuSchool of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, People's Republic of ChinaTel +86 21 5198 0041; +853 8897 2880Fax +853 2882 3575Email maoyc@fudan.edu.cn; yzzhu@must.edu.moPurpose: S-propargyl-cysteine (SPRC; alternatively known as ZYZ-802) is a novel modulator of endogenous tissue H2S concentrations with known cardioprotective and anti-inflammatory effects. However, its rapid metabolism and excretion have limited its clinical application. To overcome these issues, we have developed some novel liposomal carriers to deliver ZYZ-802 to cells and tissues and have characterized their physicochemical, morphological and pharmacological properties.Methods: Two liposomal formulations of ZYZ-802 were prepared by thin-layer hydration and the morphological characteristics of each liposome system were assessed using a laser particle size analyzer and transmission electron microscopy. The entrapment efficiency and ZYZ-802 release profiles were determined following ultrafiltration centrifugation, dialysis tube and HPLC measurements. LC-MS/MS was used to evaluate the pharmacokinetic parameters and tissue distribution profiles of each formulation via the measurements of plasma and tissues ZYZ-802 and H2S concentrations. Using an in vivo model of heart failure (HF), the cardio-protective effects of liposomal carrier were determined by echocardiography, histopathology, Western blot and the assessment of antioxidant and myocardial fibrosis markers.Results: Both liposomal formulations improved ZYZ-802 pharmacokinetics and optimized H2S concentrations in plasma and tissues. Liposomal ZYZ-802 showed enhanced cardioprotective effects in vivo. Importantly, liposomal ZYZ-802 could inhibit myocardial fibrosis via the inhibition of the TGF-β1/Smad signaling pathway.Conclusion: The liposomal formulations of ZYZ-802 have enhanced pharmacokinetic and pharmacological properties in vivo. This work is the first report to describe the development of liposomal formulations to improve the sustained release of H2S within tissues.Keywords: liposome, S-Propargyl-cysteine, SPRC, ZYZ-802, hydrogen sulfide, heart failure, myocardial fibrosis, TGF-β1/Smad pathway

As an individual, I have always valued diversity. The blending of different cultures has always been a part of my reality because of the environment where people from different tribes, ethnicity, and religion lived together in harmony. Growing up in Nigeria, the different tribes of my country were able to co-exist, more than that, they often shared the information about their different beliefs. The sharing of the different cultures helped foster a community that was accepting of people regardless of what made them different. Moving to the United States, I experienced a culture shock because I was in a new environment where difference is not celebrated, but actually comes with hostility and culture division. This realization was tough to accept. Knowing the history of the United States, I curious to understand why people were not as accepting of each other, a reality different from what I experienced coming from a different country. Through my communication studies classes, I became more aware of the roles cultural identities played in how we interact with each other. I was also more aware that good communication is the key to fostering community. Because of this, I decided to explore this topic to understand how our social identities played a role in how we communicate the differences we had. To do this, I read multiple research papers who shared my desire to bridge our community; I explore political correctness, cultural competence, cultural humility, and why difference matter. I also interviewed fifteen individuals to get their insight and have an answer to my main research question which is "what needs to happen to help people be able to communicate better about the difference?

Le Brexit a tenu l'Europe en haleine ces trois dernières années et aura des conséquences économiques et politiques majeures dans les années à venir. A l'approche d'élections qui s'annoncent déterminantes pour le Royaume-Uni, la forme que prendra le Brexit reste très incertaine. Loin de pouvoir en prédire précisément les conséquences, nous rappelons dans ce numéro deRegards économiquesles principaux enjeux du Brexit d'un point de vue économique et ses implications possibles, et nous revenons sur l'expérience des trois dernières années pour juger de son importance. En tant que membre à part entière de l'Union européenne, le Royaume-Uni fait actuellement partie du marché unique et de l'union douanière. Alors que le marché unique assure la libre circulation des biens et des services entre ses membres, l'union douanière garantit l'absence de frontières et implique une politique commerciale extérieure commune. Tous ses membres appliquent les mêmes tarifs douaniers aux importations en provenance de pays tiers. Le Royaume-Uni étant un pays qui commerce beaucoup avec les pays de l'Union européenne et les pays tiers, sortir de ces deux entités ne serait pas sans conséquence. Ceci pose la question de la frontière entre la République d'Irlande et l'Irlande du Nord, sujet encore très sensible au Royaume-Uni car il deviendrait nécessaire de réintroduire des contrôles à la frontière irlandaise. C'est la quadrature du cercle que doit résoudre un accord et la raison principale de son échec à ce jour. Les différentes solutions proposées n'ont jusqu'à maintenant pas fait consensus. Évaluer l'impact de la sortie du Royaume-Uni de l'Union européenne n'est pas simple et nécessite de trouver réponse à une série de questions connexes : le Royaume-Uni sera-t-il dans une union douanière avec l'U.E. ? Le Royaume-Uni et l'Union européenne signeront-ils un accord de libre-échange ? Le cas échéant, quelle en sera sa nature ? Les accords de retrait que Theresa May, et plus récemment Boris Johnson, ont soumis à l'Union européenne ne fixent en effet qu'un cadre global de négociations et ne prévoient rien de précis sur les détails de l'accord commercial devant être négocié au cours de la période de transition fixée à deux ans. Les travaux académiques qui ont étudié les conséquences de différents scénarios du Brexit sur l'économie britannique et ses partenaires à long terme s'accordent dans leur ensemble sur le fait que la sortie de l'U.E. sera coûteuse pour le Royaume-Uni. L'ampleur de ces coûts est néanmoins incertaine dans la mesure où celle-ci repose sur les hypothèses des modèles théoriques sous-jacents et des scénarios envisagés. Le référendum a déjà eu des conséquences sur l'économie britannique. L'annonce du résultat du vote a entraîné un changement immédiat des attentes concernant l'avenir économique du Royaume-Uni. A l'ouverture des marchés financiers, le 24 juin, la livre sterling s'est dépréciée vis-à-vis des principales monnaies (euro, dollar, yen, yuan). Selon des travaux récents, le ménage moyen britannique a vu ses dépenses de consommation augmenter de 688 livres par an, soit une semaine et demie de salaire annuel. Cette augmentation des dépenses touche autant les ménages à revenu modeste que les ménages plus aisés. L'incertitude prégnante quant à l'avenir des relations entre le Royaume-Uni et l'Union européenne a elle aussi affecté l'activité des entreprises britanniques, et aura probablement une incidence sur la croissance à plus long terme. L'investissement a ainsi diminué progressivement au cours des trois dernières années et ce surtout pour les entreprises qui commercent beaucoup avec l'U.E. Les entreprises ont également repoussé l'exportation de nouveaux biens ou cessé leurs exportations vers l'Union européenne dans l'année suivant le référendum. Dans le même temps, les entreprises britanniques investissent davantage en Union européenne. Il n'est encore pas clair à ce jour quand le Brexit aura lieu, ni même certain s'il aura bien lieu. Les élections de début décembre seront déterminantes pour la tournure qu'il prendra. L'expérience de ces trois dernières années ainsi que la nature des enjeux que le Brexit soulève laissent cependant craindre des effets non-négligeables, en particulier pour le Royaume-Uni.

Planetary defense from near-Earth objects such as asteroids is a far more nuanced and challenging topic than it might seem. Each day, technology is making it easier to detect asteroid impact threats in advance, but at present, there is still no easy way to design and implement any form of global defense.This book examines how various asteroid deflection methods can change global political affairs. The authors believe that the final policy for potential Earth impacts should be based on practical engineering solutions and innovative architectural structures, while at the same time reflecting the most recent political science contributions in ethical security studies and security cosmopolitanism. Their focus is not limited to effective engineering solutions, but rather extends to how such proposals resonate in possible political structures of the future.

YÖK Tez No: 606078 ; Yüksek Lisans ; 2011 yılının Mart ayında Suriye'de başlayan iç savaş, 8 yıldır milyonlarca Suriye vatandaşının hayatını derinden etkileyerek devam etmektedir. Savaşın en ağır bedelini ödeyenler ise hem halen Suriye içerisinde yaşayan hem de diğer ülkelere göç eden sayıları yaklaşık 5 milyonu bulan Suriyeli çocuklardır. Savaş başladığından günümüze kadar yaklaşık 5,6 milyon Suriyeli kişi savaş ve çatışmadan kaçarak başka ülkelere göç zorunlu olarak göç etmiştir, aynı zamanda 6,2 milyon kişi de Suriye içerisinde yerinden edilmiştir. Suriyeliler zorla yerlerinden edilirken, öncelikli olarak sınır komşuları Türkiye'ye sığınmışlardır. Türkiye 3,6 milyon Suriyeli mülteciye ev sahipliği yaparak, dünya'da en fazla mülteci barındıran ülke konumuna gelmiştir. Türkiye'deki Suriyeli mülteci nüfusunun neredeyse yarısını okul çağındaki çocuklar oluşturmaktadır ve bu durum mülteci eğitiminin önemini oldukça arttırmaktadır. Eğitim, mülteci çocukların maruz kaldıkları negatif durumlarla başedebilmeleri ve göç ettikleri ülkeye uyum sağlayabilmeleri için anahtar bir rol oynamaktadır. Bu çalışmada, 2011 yılından bu yana Türk Hükümetinin Suriyeli mülteci çocukların eğitim ihtiyaçlarını karşılamak için verdikleri hizmetler incelenmiş, mülteci öğrencilere uygulanan farklı eğitim sistemleri ve bu sistemlerin geçici politikalardan kalıcı politikara nasıl dönüştüğü tartışılmıştır. Aynı zamanda eğitime erişimin ve farklı eğitim sistemlerinin Suriyeli mülteci çocukların misafir eden topluma uyum sağlamasında nasıl bir önemi olduğu araştırılmıştır. Son olarak, Hatay'da yapılan saha çalışması ile eğitim hizmetlerinin erişilebilirliği, kalitesi ve kapsayıcılığı tartışılmış, aynı zamanda eğitim sürecinde karşılaşılan zorluklar ve güzel örnekler tespit edilmiştir. Tespit edilen zorluklar ve güzel örnekler üzerinden mevcut mülteci eğitim sisteminin kapsayıcılığının genişletilmesi için çeşitli politika önerilerinde bulunulmuştur. ; The civil war that started in Syria in March 2011 has been continuing for the last 8 years with a profound impact on the lives of millions of Syrian citizens. Syrian children, who are currently living in Syria and those who migrated to other countries, pay the heaviest price. Since the outbreak of the war, approximately 5,6 million Syrian refugees have fled from war and conflict and migrated to other countries. At the same time, 6,2 million people were displaced within Syria. While Syrians have been forcibly displaced, they have sought refuge primarily in their border neighbours, specifically including Turkey. Turkey is home to 3,6 million Syrian refugees which make it the largest refugee-hosting country in the world. Almost half of the Syrian refugee population in Turkey is school-age children, which greatly increases the importance of refugee education in Turkey. Education plays a key role in helping refugee children cope with the negative situations they are exposed to and adapt to the country in which they migrate. In this study, the services provided by the Turkish Government to meet the educational needs of Syrian refugee children since 2011 have been examined, the different education systems applied to refugee students and how these systems have been transformed from temporary policies to permanent policies have been discussed. It also examined how access to education and different educational systems have importance in integrating Syrian refugee children to host society. Finally, the fieldwork conducted in Hatay discussed the accessibility, quality, and inclusivity of education services, and identified the difficulties and good examples encountered in the education process. Through the identified challenges and good examples, various policy recommendations have been made to expand the inclusiveness of the current refugee education system.

Jianfeng Jin,1 Dongdong Fei,1 Yumei Zhang,2 Qintao Wang1 1State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, People's Republic of China; 2State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, People's Republic of China Background: Biological complications are an issue of critical interest in contemporary dental and orthopedic fields. Although titanium (Ti), graphene oxide (GO) or silver (Ag) particles are suitable for biomedical implants due to their excellent cytocompatibility, bioactivity, and antibacterial properties, the exact antibacterial mechanism is not understood when the three substances are combined (Ti-GO-Ag). Materials and methods: In this work, the material characterization, antibacterial property, antibacterial mechanisms, and cell behavior of Ti-GO-Ag fabricated by electroplating and ultraviolet reduction methods respectively, were investigated in detail. Results: The material char­acterization of Ti-GO-Ag tested by atomic force microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, nanoindentation, nanoscratch, inductively coupled plasma mass spectrometer, and contact angle tester revealed the importance of GO concentration and Ag content in the preparation process. The antibacterial tests of Ti-GO-Ag clearly demonstrated the whole process of bacteria interacting with materials, including reactive oxygen species, endocytosis, aggregation, perforation, and leakage. In addition, the behavior of Ti-GO-Ag showed that cell area, length, width, and fluorescence intensity were affected. Conclusion: Briefly, Ti-GO-Ag nanocomposite was a dual-functionalized implant biomaterial with antibacterial and biocom­patible characterization. Keywords: functionalized titanium implant, Ti-GO-Ag nanocomposite, surface topography, material characterization, antibacterial mechanism, cell behavior

Bo Jian,1,2 Wei Wu,2 Yingliang Song,1 Naiwen Tan,3 Chao Ma1 1State Key Laboratory of Military Stomatology, Department of Implant Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China; 2Department of Oral & Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China; 3Department of Stomatology, Hospital 463 of PLA, Shenyang, Liaoning, People's Republic of China Purpose: We aimed to fabricate guided bone regeneration (GBR) membrane using polyglycerol sebacate (PGS) and investigate the impact of scaffold pore size on osteogenesis.Materials and methods: PGS microporous membrane was fabricated by salt-leaching technique with various pore sizes. Twenty-eight male New Zealand rabbits were randomly divided into four groups: 25 µm PGS membrane, 53 µm PGS membrane, collagen membrane, and blank control group. Subsequently, standardized and critical-sized tibia defects were made in rabbits and the defective regions were covered with the specifically prepared membranes. After 4 and 12 weeks of in vivo incubation, bone samples were harvested from tibia. Micro-computed tomography scanning was performed on all bone samples. A three-dimensional visible representation of the constructs was obtained and used to compare the ratios of the ossifying volume to total construct volume (bone volume to tissue volume [BV/TV]) of each sample in different groups; then, bone samples were stained with H&E and Masson's trichrome stain for general histology.Results: At 4 weeks, the BV/TV in the 25 µm PGS group was found higher than that in the 53 µm PGS and collagen groups. At 12 weeks, the bone defect site guided by the 25 µm PGS membrane was almost completely covered by the new bone. However, the site guided by the 53 µm PGS membrane or collagen membrane was covered only most of the defects and the left part of the defect was unoccupied. Histological observation further verified these findings.Conclusion: We thus concluded that the 25 µm PGS membrane played an advantageous role during 4–12 weeks as compared with those earlier degraded counterparts. Keywords: bone defect, biological membrane, degradation, salt-leaching technique, tibia

Menglong Liu,1 Tengfei Liu,1 Xiaorong Zhang,1 Zhiwen Jian,2 Hesheng Xia,2 Jiacai Yang,1 Xiaohong Hu,1 Malcolm Xing,1,3 Gaoxing Luo,1 Jun Wu1,41Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, People's Republic of China; 2State Key Laboratory of Polymer Materials Engineering, Polymer Research Institute of Sichuan University, Chengdu, 610065, People's Republic of China; 3Department of Mechanical Engineering, University of Manitoba, Winnipeg, MB R3T 2N2, Canada; 4Department of Burns, the First Affiliated Hospital, SunYat-Sen University, Guangzhou 510080, People's Republic of ChinaBackground: Designing a wound dressing that effectively prevents multi-drug-resistant bacterial infection and promotes angiogenesis and re-epithelialization is of great significance for wound management.Methods and results: In this study, a biocompatible composite membrane comprising biomimetic polydopamine-modified eggshell membrane nano/microfibres coated with KR-12 antimicrobial peptide and hyaluronic acid (HA) was developed in an eco-friendly manner. The physicochemical properties of the composite membrane were thoroughly characterized, and the results showed that the surface hydrophilicity and water absorption ability of the composite membrane were improved after the successive conjugation of the HA and the KR-12 peptide. Furthermore, the in vitrobiological results revealed that the composite membrane had excellent antibacterial activity against Gram-positive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli, and it could prevent MRSA biofilm formation on its surface. Additionally, it promoted the proliferation of keratinocytes and human umbilical vein endothelial cells and increased the secretion of VEGF. Finally, an in vivo animal study indicated that the composite membrane could promote wound healing via accelerating angiogenesis and re-epithelialization, which were demonstrated by the enhanced expression of angiogenetic markers (CD31 and VEGF) and keratinocyte proliferation marker (PCNA), respectively.Conclusion: These results indicated that the composite membrane is a potential candidate of wound dressingsKeywords: antimicrobial peptides, hyaluronic acid, fibrous eggshell membrane, antibacterial activity, angiogenesis, re-epithelialization

Pan Shang,1,* Gan Chen,1,* Guannan Zu,2 Xiang Song,1 Peng Jiao,2 Guoxing You,1 Jingxiang Zhao,1 Hongyi Li,2 Hong Zhou11Academy of Military Medical Sciences, Institute of Health Service and Transfusion Medicine, Beijing 100850, People's Republic of China; 2Photoelectrochemical Research Group, School of Materials Science and Engineering, Beijing University of Technology, Beijing 100124, People's Republic of China *These authors contributed equally to this workBackground: Cardiovascular disease (CVD) is the leading cause of mortality all over the world. Vascular stents are used to ameliorate vascular stenosis and recover vascular function. The application of nanotubular coatings has been confirmed to promote endothelial cell (EC) proliferation and function. However, the regulatory mechanisms involved in cellular responses to the nanotubular topography have not been defined. In the present study, a microarray analysis was performed to explore the expression patterns of long noncoding RNAs (lncRNAs) in human coronary artery endothelial cells (HCAECs) that were differentially expressed in response to nitinol-based nanotubular coatings.Materials and methods: First, anodization was performed to synthesize nitinol-based nanotubular coatings. Then, HCAECs were cultured on the samples for 24 h to evaluate cell cytoskeleton organization. Next, total RNA was extracted and synthesized into cRNA, which was hybridized onto the microarray. GO analysis and KEGG pathway analysis were performed to investigate the roles of differentially expressed messenger RNAs (mRNAs). Quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) was performed to validate the expression of randomly selected lncRNAs. Coexpression networks were created to identify the interactions among lncRNAs and the protein-coding genes involved in nanotubular topography-induced biological and molecular pathways. Independent Student's t-test was applied for comparisons between two groups with statistical significance set at p<0.05.Results: 1085 lncRNAs and 227 mRNAs were significantly differentially expressed in the nitinol-based nanotubular coating group. Bioinformatics analysis revealed that extracellular matrix receptor interactions and cell adhesion molecules play critical roles in the sensing of nitinol-based nanotubular coatings by HCAECs. The TATA-binding protein (TBP) and TBP-associated transfactor 1 (TAF1) are important molecules in EC responses to substrate topography.Conclusion: This study suggests that nanotubular substrate topography regulates ECs by differentially expressed lncRNAs involved extracellular matrix receptor interactions and cell adhesion molecules.Keywords: nitinol titanium dioxide nanotubes, RNA sequencing, long noncoding RNA, nanotopography, molecular networks

Wei Wu,1,* Yan-Qing Yang,2,* Yang Yang,1,* Yu-Ming Yang,2 Hong Wang,2 Kai-Yuan Zhang,1 Li Guo,3 Hong-Fei Ge,1 Jie Liu,2 Hua Feng11Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, People's Republic of China; 2Key Laboratory of Flexible Electronics (KLOFE) Institute of Advanced Materials (IAM), Nanjing Tech University, Nanjing 211800, People's Republic of China; 3Department of Endocrinology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, People's Republic of China*These authors contributed equally to this workBackground: In vivo fluorescence imaging in the second near-infrared (NIR-II, 1000–1700 nm) window using organic fluorophores has great advantages, but generally suffers from a relatively low fluorescence quantum yield (mostly less than 2%). In this study, organic nanoparticles (L1013 NPs) with a high fluorescence quantum yield (9.9%) were systhesized for in vivo imaging.Methods: A molecule (BTPPA) with donor-acceptor-donor structure and aggregation-induced emission enabling moieties was prepared. BTPPA molecules were then encapsulated into nanoparticles (L1013 NPs) using a nanoprecipitation method. The L1013 NPs were intravenously injected into the mice (including normal, stroke and tumor models) for vascular and tumor imaging.Results: L1013 NPs excited at 808 nm exhibit NIR-II emission with a peak at 1013 nm and an emission tail extending to 1400 nm. They have a quantum yield of 9.9% and also show excellent photo/colloidal stabilities and negligible in vitro and in vivo toxicity. We use L1013 NPs for noninvasive real-time visualization of mouse hindlimb and cerebral vessels (including stroke pathology) under a very low power density (4.6–40 mW cm‒2) and short exposure time (40–100 ms). Moreover, L1013 NPs are able to localize tumor pathology, with a tumor-to-normal tissue ratio of 11.7±1.3, which is unusually high for NIR-II fluorescent imaging through passive targeting strategy.Conclusion: L1013 NPs demonstrate the potential for a range of clinical applications, especially for tumor surgery.Keywords: fluorescence NIR-II imaging, aggregation-induced emission, organic nanoparticle, vascular imaging, tumor imaging