EngRN: Biomedical Engineering (Topic)最新文献

{"title":"Radiosensitization With Nanoparticles Targeting to Mitochondria","authors":"Jun Xue, Dida Duosiken, S. Zhong, Jiao-Jiao Cao, Liang-Yun Hu, Kang Sun, Ke Tao, Sijian Pan","doi":"10.2139/ssrn.3802819","DOIUrl":"https://doi.org/10.2139/ssrn.3802819","url":null,"abstract":"Sensitizing radiation therapy (RT) for cancer is highly desired to reduce side-effect of the harsh dose of irradiation, and nanoparticles with high atomic number elements provide a promising tool. However, insufficient knowledge on utilizing the interaction between nanoparticles and cancerous cells hampers the improvement of therapeutic outcome. We herein employed NaGdF4:Yb,Er nanocrystals as the sensitizer, and modified them with a tumor targeting agent and a mitochondria targeting moiety, separately and jointly, to achieve varied extent of mitochondrial accumulation. We observed that NaGdF4:Yb,Er nanocrystal, even unmodified with targeting ligands, is effective for radiosensitization. Furthermore, the extent of mitochondrial targeting was responsible for sensitization efficiency both in vitro and in vivo. By RNA sequencing (RNA-seq) technique, the result was ascribed to the reactive oxygen species (ROS) mediated TNF-JNK pathway and cell cycle arrest, rather than breaking DNA with those untargeted nanoparticles. Our work indicated that ROS generated by the irradiation can be utilized by activating an alternative apoptotic pathway with mitochondrial targeting nanoparticles, and therefore may suggest an approach for the enhancement of radiosensitization.","PeriodicalId":131242,"journal":{"name":"EngRN: Biomedical Engineering (Topic)","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129677748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Split-Enzyme Immunoassay to Monitor EGFR-HER2 Heterodimerization on Cell Surfaces","authors":"S. J. Kim, Andrew S. Dixon, S. Owen","doi":"10.2139/ssrn.3751570","DOIUrl":"https://doi.org/10.2139/ssrn.3751570","url":null,"abstract":"Over 30,000 protein-protein interactions with pathological implications have been identified; yet, discovering and investigating drugs that target these specific interactions is greatly limited by the inability to monitor native protein-protein interactions (PPIs) efficiently. The two most frequently used tools to monitor PPIs, resonance-energy transfer (RET) assays and protein complementation assays (PCA), face significant limitations. RET assays have a narrow working range of 10 to 50 Å, while PCA require permanent attachment of a reporter probe to a protein of interest by chemical conjugation or genetic engineering. We developed a non-invasive assay platform to measure PPIs without modifications to the proteins of interest and is functional at a greater working range than RET assays. We demonstrate our approach by monitoring the EGFR-HER2 heterodimerization on relevant cell surfaces, utilizing various EGFR- and HER2-specific binders (e.g., Fab, DARPin, and VHH) fused with small fragments of a tri-part split-luciferase derived from NanoLuc®. Following independent binding of the binder fusions to their respective targets, the dimerization of EGFR and HER2 induces complementation of the luciferase fragments into a functional native structure, producing glow-type luminescence. We have confirmed the functionality of the platform to monitor EGFR-HER2 dimerization induction and inhibition. STATEMENT OF SIGNIFICANCE: : We describe a platform technology for rapid monitoring of protein-protein interactions (PPIs). Our approach is uses a luciferase split into three parts - two short peptide \"tags\" and a large third fragment. Each of the short peptides can be fused to antibodies which bind to domains of a target antigens which orients the two tags and facilitates refolding of an active enzyme. To our knowledge this is the first example of a split-enzyme used to monitor PPIs without requiring any modification of the target proteins. We demonstrate our approach on the important PPI of HER2 and EGFR. Significantly, we quantify stimulation and inhibition of these partners, opening the possibility of using our approach to assess potential drugs without engineering cells.","PeriodicalId":131242,"journal":{"name":"EngRN: Biomedical Engineering (Topic)","volume":"38 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115099844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steroid-Eluting Contact Lenses for Corneal and Intraocular Inflammation","authors":"Lokendrakumar C. Bengani, H. Kobashi, A. Ross, H. Zhai, Borja Salvador-Culla, Rekha Tulsan, P. Kolovou, S. Mittal, S. Chauhan, D. Kohane, J. Ciolino","doi":"10.2139/ssrn.3627992","DOIUrl":"https://doi.org/10.2139/ssrn.3627992","url":null,"abstract":"Ocular inflammation is one of the leading causes of blindness worldwide, and steroids in topical ophthalmic solutions (e.g. dexamethasone eye drops) are the mainstay of therapy for ocular inflammation. For many non-infectious ocular inflammatory diseases, such as uveitis, eye drops are administered as often as once every hour. The high frequency of administration coupled with the side effects of eye drops leads to poor adherence for patients. Drug-eluting contact lenses have long been sought as a potentially superior alternative for sustained ocular drug delivery; but loading sufficient drug into contact lenses and control the release of the drug is still a challenge. A dexamethasone releasing contact lens (Dex-Lens) was previously developed by encapsulating a dexamethasone-polymer film within the periphery of a hydrogel-based contact lens. Here, we demonstrate safety and efficacy of the Dex-Lens in rabbit models in the treatment of anterior ocular inflammation. The Dex-Lens delivered drug for 7 days in vivo (rabbit model). In an ocular irritation study (Draize test) with Dex-Lens extracts, no adverse events were observed in normal rabbit eyes. Dex-Lenses effectively inhibited suture-induced corneal neovascularization and inflammation for 7 days and lipopolysaccharide-induced anterior uveitis for 5 days. The efficacy of Dex-Lenses was similar to that of hourly-administered dexamethasone eye drops. In the corneal neovascularization study, substantial corneal edema was observed in rabbit eyes that received no treatment and those that wore a vehicle lens as compared to rabbit eyes that wore the Dex-Lens. Throughout these studies, Dex-Lenses were well tolerated and did not exhibit signs of toxicity. Dexamethasone-eluting contact lenses may be an option for the treatment of ocular inflammation and a platform for ocular drug delivery.","PeriodicalId":131242,"journal":{"name":"EngRN: Biomedical Engineering (Topic)","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131661756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning Approach for Predicting Breast Cancer Using Genomic Data","authors":"Saurabh Sharma, Neel Shah, R. Singh, Reena Lokare","doi":"10.2139/ssrn.3571724","DOIUrl":"https://doi.org/10.2139/ssrn.3571724","url":null,"abstract":"Cancer prediction at an early stage is very crucial as the patient can then prepare for dealing with it. There are several Machine Learning models that help in predicting cancer by identifying samples of independent persons at high risk, facilitating the design and planning of cancer trials. These models use biomarkers like age, menopause, tumor-size, invnodes, breast, breast-quad dimensions to predict breast cancer. However, these models had major drawbacks of late prediction as well as low accuracy. So here presenting the system which uses gene expression profiles (genomic data) to predict breast cancer at an early stage. This model is built using different machine learning algorithms like a highly versatile support vector machine (SVM), Naive Bayes theorem, Decision tree and nearest neighbors approach to predict breast cancer using gene expression profiles.","PeriodicalId":131242,"journal":{"name":"EngRN: Biomedical Engineering (Topic)","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129978598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microstructure, Mechanical Properties, and Corrosion Behavior of New βtype Ti–Mo–Nb Based Alloys by Mn Addition for Implant Material","authors":"C. Sutowo, S. Supriadi, A. Pramono, B. Suharno","doi":"10.15587/1729-4061.2020.193932","DOIUrl":"https://doi.org/10.15587/1729-4061.2020.193932","url":null,"abstract":"Titanium alloys are widely used for biomaterial applications since they have special characteristics, especially better biocompatibility, superior corrosion behavior and lower modulus of elasticity compared to other conventional biomaterials. The development of existing Ti6Al4V alloys by creating new β-type Ti-Mo-Nb based alloys by modifying the addition of the Mn element as a beta phase stabilizer, so that the beta phase structure can have an effect to increase strength and reduce elastic modulus with good biocompatibility and toxicity. In the present work, Ti–Mo–Nb–(x)Mn alloys (x=0, 4, 8, and 12, mass fraction in  %) were prepared using an electric vacuum arc furnace with a tungsten electrode. The samples were homogenized at 1050°C for 6 h under a controlled argon atmosphere, and the effects of adding Mn on the mechanical properties and corrosion behavior of the alloys were investigated using X-ray fluorescence spectroscopy, X-ray diffraction, optical microscopy, hardness and ultrasonic tests, and potentiodynamic polarization test. The experimental results show that adding 4 %, 8 %, and 12 %Mn to a Ti–9Mo–6Nb alloy stabilizes the formation of the β-phase titanium, implying that the alloys have similar microstructures but different grain sizes. Potentiodynamic polarization measurements show that an increase of the Mn content in the Ti–9Mo–6Nb alloy decreases the corrosion resistance. At 4 %Mn, the alloy has an elastic modulus of 93 GPa and better corrosion resistance, with a relatively low corrosion rate amounting to 0.00290 mm per year, than those of a commercial Ti–6Al–4V alloy","PeriodicalId":131242,"journal":{"name":"EngRN: Biomedical Engineering (Topic)","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128533515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theoretical Investigation on Terahertz Wave Radiation From Ion Transport in the Calcium Membrane Channel","authors":"Lianghao Guo, Wenfei Bo, Kaicheng Wang, Shaomeng Wang, Y. Gong","doi":"10.2139/ssrn.3881352","DOIUrl":"https://doi.org/10.2139/ssrn.3881352","url":null,"abstract":"In this paper, a mathematical physics model is set up to study the terahertz (THz) wave radiation as Ca²⁺ transports in the calcium membrane channel. By means of the proposed model, the energy distribution in the three dimensional membrane channel, and the trajectories of ions under THz irradiation are analyzed. It is observed that the Ca²⁺ transmembrane transport time is in the scale of picosecond, corresponding the spectrum concentrated in the THz range. Meanwhile, both the ion number in the membrane channel and the temperature have significant effects on the spectrum. In the multi-ion channel, the frequency change of the radiation spectrum of the multi-ion system is slight compared to the single-ion channel, but the total radiation energy increases obviously. In addition, the increase of temperature will accelerate the thermal motion of ions and lead to the radiation spectrum shifting towards high frequencies. Brownian dynamics (BD) simulations are carried out to demonstrate greatly enhanced permeation of the calcium channel in reaction to an external THz wave, i.e., the amplitude and frequency of which increase, the ion transport rate across the channel increases significantly. These discoveries are expected to provide a theoretical basis for the future treatment of THz waves in the neurological field.","PeriodicalId":131242,"journal":{"name":"EngRN: Biomedical Engineering (Topic)","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125370825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclic Deformation Behavior and Related Micro-Mechanisms of Ni-Carbonyl Chemical Vapor Deposited (CVD) Material with Bimodal Grain Structures: Ultrafine (UF) Grains and Large Grains with UF/Nano Twins","authors":"Shao-Wei Fu, T. Hsu, Zhirui Wang","doi":"10.2139/ssrn.3441464","DOIUrl":"https://doi.org/10.2139/ssrn.3441464","url":null,"abstract":"Stress-controlled cyclic tests were conducted on bulk sheet Ni-carbonyl Chemical Vapor Deposited material (CVD Ni) with bimodal grain structures: ultrafine (UF) grains and large grains with UF/nano twins. The tests were run with the cyclic stress ratio R=0.05 and peak stress level of 0.9 to 1.5 times of the material's yield strength. Results show that within the applied peak stress ratio of 0.9-1.1, the material demonstrated cyclic hardening behavior first, followed by stress-strain saturation till fracture; upon increasing the ratio to 1.4-1.5, an additional softening stage was activated and continued till fracture. By transmission electron microscope (TEM) examination, it was found that such cyclic deformation responses were associated with the stability of the ultrafine- and nano-twin structures. Initial hardening was found mainly due to the increase in dislocation density and the activities of dislocations especially with their strong interactions with the dense Twin Boundaries (TBs). The saturation was contributed by the simultaneous operations of the softening effect due to massive detwinning and the hardening behavior due to dislocation interactions with existing TBs. Newly formed dislocation walls and cell structures were further found in samples with stress ratio of 1.4 at fracture, corresponding to the softening stage. Furthermore, such microstructural evolution, which were observed also through annealing and monotonic deformation of the same material, is identified as a consistent energy reduction path for the material. Thus, an energy criterion is further established to predict the massive detwinning events that cause the major softening phenomena under cyclic deformation.","PeriodicalId":131242,"journal":{"name":"EngRN: Biomedical Engineering (Topic)","volume":"75 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115643008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endosomal Escapable Cryo-Treatment Driven Membrane Encapsulated Ga Liquid-Metal Transformer to Facilitate Intracellular Therapy","authors":"Xuelin Wang, Xuedong Li, M. Duan, Shaobo Shan, Xiyu Zhu, Yi Wen Chai, Hongzhang Wang, Xuyang Sun, Lei Sheng, Wei Rao, Liang Hu, Junge Chen, Jing Liu","doi":"10.2139/ssrn.3876700","DOIUrl":"https://doi.org/10.2139/ssrn.3876700","url":null,"abstract":"Metallic/nonmetallic shape transformable materials hold big promise for improved intracellular therapy with efficient endosomal escape in tumor treatments. However, until now, there are still rather limited biomedical practices for such materials which are mainly attributed to their inherent uncontrolled morphological transformation, difficult metabolization, accumulated toxicity, non-selective destruction and difficult real-time imaging. In this study, Ga-based liquid metal, with distinct properties of high thermal conductivity, excellent phase transition, injectability, targetability, easy-preparation and biosafety, is found to exhibit remarkable transformation from sphere shape to cactus-like structure in micro-scale under freezing. Particularly, it is revealed that only cell membrane-encapsulated Ga particles (Ga/MPs) display dramatic shape variation in cooling under Cryo-TEM contrasting to pure Ga particles (GaPs). Following that, the cryo-triggered Ga/MPs transformers are designed for effective endosomal escape via physical-mechanical strategy to disrupt endosomal membrane which lead to highly efficient cancer cell killing. Moreover, under <i>in vivo</i> antitumor treatments settings, Ga/MPs exhibit significant tumor growth inhibition and prolonged survival time to evaluate the collaborative efficacy of cryoablation and endosomal escape mechanism, as well high-resolution <i>in vivo</i> CT imaging is achieved. This study opens a favorable and versatile strategy based on Ga particle transformer to assist high-performance precise intracellular therapy in future tumor therapeutics.","PeriodicalId":131242,"journal":{"name":"EngRN: Biomedical Engineering (Topic)","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115217144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustainable Quercetin@Functionalized Carbon Nanotubes as Semi-TCFsAnd/Or 3D Printing Inks in Presence of Gelatin","authors":"M. Fares, Samah Radaydeh","doi":"10.2139/ssrn.3897767","DOIUrl":"https://doi.org/10.2139/ssrn.3897767","url":null,"abstract":"Semi-Transparent conductive films (semi-TCFs) were fabricated from sustainable onion quercetin and functionalized carbon nanotubes (F-CNTs) in presence of different metal ion crosslinking agents via layer-by-layer technique. Moreover, 3D printing inks and injectable hydrogels were fabricated from sustainable onion quercetin and functionalized carbon nanotubes (F-CNTs) in presence gelatin. Synthesis and characterization of sustainable quercetin and functionalized CNTs were performed using spectroscopic, thermal, microscopic techniques; 1H-NMR, and ATR-FTIR for chemical structure, XRD for crystal structure, TGA and DTG for thermal stability, and SEM for morphologic nanostructure. Layer-by-layer semi-TCFs were fabricated in presence of crosslinking agent of metal ions like Ca2+, Ti2+, Sn2+, and Fe3+ ions, where transmittance was in the range of 41-67%, sheet resistance in 17-1567 kΩ/sq, and σdc/σop in 0.0005-0.02 range, which undoubtly confirm their semi-TCFs characteristics. Optimum performance of single-layer F-CNTs semi-TCFs was as follows; transmittance= 46.6%, sheet resistance= 6.5 kΩ/sq, and σdc/σop= 0.06. On the other hand, 3D printing ink of sustainable quercetin and Functionalized CNTs in presence of gelatin was fabricated. Semi-Interpenetrating network hydrogel was verified through spectroscopic ATR-FTIR technique. The injectable hydrogel showed promising characteristics of robustness, elasticity, anti-microbial activity, biocompatibility with human body, and stretchable low cost that adapt them to be successfully employed in biomedical and surgical applications.","PeriodicalId":131242,"journal":{"name":"EngRN: Biomedical Engineering (Topic)","volume":"52 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134537879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}