95 results on '"Linbo Liu"'
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2. Exosomes derived from epidermal growth factor-like domain protein 6-preconditioned mesenchymal stem cells for diabetic wound healing
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Chen Gong, Chengde Xia, and Linbo Liu
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Diabetic wound healing ,Mesenchymal stem cells ,Epidermal growth factor-like domain protein 6 ,Exosomes ,Hydrogel ,Medicine (General) ,R5-920 ,Cytology ,QH573-671 - Abstract
Diabetic wounds are difficult to repair effectively in the clinic. Tissue engineering based on mesenchymal stem cells (MSCs) showed great therapeutic potential in wound healing. MSCs-derived exosome could reproduce the effect of MSCs by transferring the bioactive substance to the recipient cells. The biological function of exosomes was determined by the state of the derived MSCs. In this study, we cultured hUC-MSCs with EGFL6 and isolated EGFL6-preconditioned exosomes (EGF-Exos), and then investigated the effect of EGF-Exos on wound healing. The results revealed that EGF-Exos promoted the proliferation and migration of HUVECs, had the anti-inflammtory function and improved angiogenesis. Moreover, we fabricated Gelama hydrogel to load EGF-Exos to repair diabetic wounds. In vivo results showed that EGF-Exos contributed to the repair of diabetic wound and provided valuable data for understanding the role of EGF-Exos in diabetic wound healing.
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- 2024
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3. Physiological and metabolomic analyses reveal the mechanism by which exogenous spermine improves drought resistance in alfalfa leaves (Medicago sativa L.)
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Wenjuan Wang, Wenjuan Kang, Shangli Shi, and Linbo Liu
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alfalfa ,exogenous ,spermine ,physiological ,metabolomics ,drought resistance ,Plant culture ,SB1-1110 - Abstract
IntroductionAlfalfa (Medicago sativa L.) is a globally important legume crop with high nutritional and ecological value. Drought poses a serious threat to alfalfa acreage and yields. Spermine (Spm) has been shown to protect plants from drought damage. The aim of this study was to clarify the mechanism of exogenous Spm to improve drought resistance of alfalfa. MethodsIn this study, we root applied 0.1, 0.5, and 1 mM Spm to Gannong No. 3 (G3) alfalfa under drought stress, and then determined their physiological and metabolic changes. ResultsThe results showed that exogenous Spm increased chlorophyll content, chlorophyll fluorescence parameters and gas exchange parameters, enhanced antioxidant enzymes activity, improved ascorbic acid-glutathione (AsA-GSH) cycle, increased osmoregulatory substances content, reduced hydrogen peroxide and superoxide anion levels, and inhibited malondialdehyde accumulation in alfalfa under drought stress, thereby increasing plant height and leaf relative water content and enhancing drought tolerance of alfalfa. The redundancy analysis of the above physiological indicators showed that the addition of the optimal Spm to improve drought tolerance of alfalfa under drought stress was mainly achieved by increasing catalase activity and improving the ASA-GSH cycle. In addition, metabolomics analysis revealed that exogenous Spm increased the content of oxobutanedioic acid, citric acid, fumaric acid and malic acid to enhance the tricarboxylic acid cycle. Meanwhile, exogenous Spm increased endogenous Spm and proline (Pro) content to resist drought stress by enhancing Spm and Pro metabolism. Moreover, exogenous Spm increased the accumulation of the signaling substance abscisic acid. DiscussionIn conclusion, exogenous Spm enhanced drought resistance of alfalfa leaves under drought stress.
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- 2024
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4. Deblurring, artifact-free optical coherence tomography with deconvolution-random phase modulation
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Xin Ge, Si Chen, Kan Lin, Guangming Ni, En Bo, Lulu Wang, and Linbo Liu
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deconvolution ,random phase masks ,deblurring ,Optics. Light ,QC350-467 ,Applied optics. Photonics ,TA1501-1820 - Abstract
Deconvolution is a commonly employed technique for enhancing image quality in optical imaging methods. Unfortunately, its application in optical coherence tomography (OCT) is often hindered by sensitivity to noise, which leads to additive ringing artifacts. These artifacts considerably degrade the quality of deconvolved images, thereby limiting its effectiveness in OCT imaging. In this study, we propose a framework that integrates numerical random phase masks into the deconvolution process, effectively eliminating these artifacts and enhancing image clarity. The optimized joint operation of an iterative Richardson-Lucy deconvolution and numerical synthesis of random phase masks (RPM), termed as Deconv-RPM, enables a 2.5-fold reduction in full width at half-maximum (FWHM). We demonstrate that the Deconv-RPM method significantly enhances image clarity, allowing for the discernment of previously unresolved cellular-level details in nonkeratinized epithelial cells ex vivo and moving blood cells in vivo.
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- 2024
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5. Method for Extracting Optical Element Information Using Optical Coherence Tomography
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Jiucheng Nie, Yukun Wang, Dacheng Wang, Yue Ding, Chengchen Zhou, Jincheng Wang, Shuangshuang Zhang, Junwei Song, Mengxue Cai, Junlin Wang, Zhongxu Cui, Yuhan Hou, Si Chen, Linbo Liu, and Xiaokun Wang
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spectral-domain OCT ,thickness measurement ,curvature measurement ,multilayer film ,Chemical technology ,TP1-1185 - Abstract
This study examines the measurement of film thickness, curvature, and defects on the surface or inside of an optical element using a highly accurate and efficient method. This is essential to ensure their quality and performance. Existing methods are unable to simultaneously extract the three types of information: thickness, curvature, and defects. Spectral-domain optical coherence tomography (SD-OCT), a non-invasive imaging technique with imaging depths down to the millimeter scale, provides the possibility of detecting the optical element components’ parameters. In this paper, we propose an error correction model for compensating delay differences in A-scan, field curvature, and aberration to improve the accuracy of system fitting measurements using SD-OCT. During data processing, we use the histogram-equalized gray stretching (IAH-GS) method to deal with strong reflections in the thin film layers inside the optics using individual A-scan averages. In addition, we propose a window threshold cutoff algorithm to accurately identify defects and boundaries in OCT images. Finally, the system is capable of rapidly detecting the thickness and curvature of film layers in optical elements with a maximum measurement depth of 4.508 mm, a diameter of 15 × 15 mm, a resolution of 5.69 microns, and a sampling rate of 70 kHz. Measurements were performed on different standard optical elements to verify the accuracy and reliability of the proposed method. To the best of our knowledge, this is the first time that thickness, curvature, and defects of an optical film have been measured simultaneously, with a thickness measurement accuracy of 1.924 µm, and with a difference between the calibrated and nominal curvature measurements consistently within 1%. We believe that this research will greatly advance the use of OCT technology in the testing of optical thin films, thereby improving productivity and product quality.
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- 2024
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6. Overexpression of ZxABCG11 from Zygophyllum xanthoxylum enhances tolerance to drought and heat in alfalfa by increasing cuticular wax deposition
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Linbo Liu, Aike Bao, Hujun Li, Wanpeng Bai, Haishuang Liu, Ye Tian, Yiying Zhao, Fangchen Xia, and Suomin Wang
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Alfalfa ,ZxABCG11 ,Cuticular wax ,Yield ,Stress tolerance ,Agriculture ,Agriculture (General) ,S1-972 - Abstract
Drought and heat stresses cause yield losses in alfalfa, a forage crop cultivated worldwide. Improving its drought and heat tolerance is desirable for maintaining alfalfa productivity in hot, arid regions. Cuticular wax forms a protective barrier on aerial surfaces of land plants against environmental stresses. ABCG11 encodes an ATP binding cassette (ABC) transporter that functions in the cuticular wax transport pathway. In this study, ZxABCG11 from the xerophyte Zygophyllum xanthoxylum was introduced into alfalfa by Agrobacterium tumefaciens-mediated transformation. Compared to the wild type (WT), transgenic alfalfa displayed faster growth, higher wax crystal density, and thicker cuticle on leaves under normal condition. Under either drought or heat treatment in greenhouse conditions, the plant height and shoot biomass of transgenic lines were significantly higher than those of the WT. Transgenic alfalfa showed excellent growth and 50% greater hay yield than WT under field conditions in a hot, arid region. Overexpression of ZxABCG11 up-regulated wax-related genes and resulted in more cuticular wax deposition, which contributed to reduction of cuticle permeability and thus increased water retention and photosynthesis capacity of transgenic alfalfa. Thus, overexpression of ZxABCG11 can simultaneously improve biomass yield, drought and heat tolerance in alfalfa by increasing cuticular wax deposition. Our study provides a promising avenue for developing novel forage cultivars suitable for planting in hot, arid, marginal lands.
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- 2023
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7. Comparative Physiological and Transcriptomic Analyses of Oat (Avena sativa) Seedlings under Salt Stress Reveal Salt Tolerance Mechanisms
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Xiangrui Zhou, Miaomiao Wang, Li Yang, Wenping Wang, Yuehua Zhang, Linbo Liu, Jikuan Chai, Huan Liu, and Guiqin Zhao
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oat ,salt stress ,transcriptome ,molecular mechanism ,DEGs ,Botany ,QK1-989 - Abstract
Soil salinity is a major abiotic stress limiting crop production globally. Oat (Avena sativa) is an annual cereal with a strong salt tolerance, a high yield, and nutritional quality, although the mechanisms underlying its salt stress response remain largely unknown. We examined the physiological and transcriptomic responses of A. sativa seedlings to salt stress in tolerant cultivar Qingyongjiu 195 and sensitive cultivar 709. Under salt stress, Qingyongjiu 195 maintained a higher photosynthetic efficiency, antioxidant enzymes activity, and leaf K+ accumulation but a lower Na+ uptake than 709. RNA-seq revealed 6616 differentially expressed genes (DEGs), including 4265 up- and 2351 downregulated. These were enriched in pathways like plant–pathogen interaction, phenylpropanoid biosynthesis, and MAPK signaling. We specifically highlight DEGs involved in photosynthesis (chlG, CP47 psbB, COX2, LHCB) and antioxidants (trxA, GroES). Qingyongjiu 195 also appeared to enhance K+ uptake via KAT1 and AKT2 and sequester Na+ in vacuoles via NHX2. Additionally, HKT restricted Na+ while promoting K+ transport to shoots, maintaining K+/Na+. The expression levels of CAX, ACA, CML, CaM, and CDPK in Qingyongjiu 195 were higher than those in 709. Oats regulated Ca2+ concentration through CAX and ACA after salt stress, decoded Ca2+ signals through CML, and then transferred Ca2+ signals to downstream receptors through the Ca2+ sensors CaM and CDPK, thereby activating K+/Na+ transporters, such as SOS1 and NHX, etc. Our results shed light on plant salt stress response mechanisms and provide transcriptomic resources for molecular breeding in improving salt tolerance in oats.
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- 2024
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8. Impact of Porphyromonas gingivalis-odontogenic infection on the pathogenesis of non-alcoholic fatty liver disease
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Linbo Liu, Yan Geng, and Chaoliang Xiong
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Porphyromonas gingivalis ,non-alcoholic fatty liver disease ,hepatic steatosis ,insulin resistance ,inflammation ,intestinal microbiota ,Medicine - Abstract
AbstractAim: Non-alcoholic fatty liver disease is characterized by diffuse hepatic steatosis and has quickly risen to become the most prevalent chronic liver disease. Its incidence is increasing yearly, but the pathogenesis is still not fully understood. Porphyromonas gingivalis (P. gingivalis) is a major pathogen widely prevalent in periodontitis patients. Its infection has been reported to be a risk factor for developing insulin resistance, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and metabolic syndrome. The aim of this review is to evaluate the association between P. gingivalis infection and NAFLD, identify the possible etiopathogenetic mechanisms, and raise public awareness of oral health to prevent and improve NAFLD.Methods: After searching in PubMed and Web of Science databases using ‘Porphyromonas gingivalis’, ‘non-alcoholic fatty liver disease’, and ‘hepatic steatosis’ as keywords, studies related were compiled and examined.Results: P. gingivalis infection is a direct risk factor for NAFLD based on clinical and basic research. Moreover, it induces systematic changes and systemic abnormalities by disrupting metabolic, inflammatory, and immunologic homeostasis.Conclusion: P. gingivalis-odontogenic infection promotes the occurrence and development of NAFLD. Further concerns are needed to emphasize oral health and maintain good oral hygiene for the prevention and treatment of NAFLD.
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- 2023
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9. The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi
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Louisa L. Y. Chan, Danielle E. Anderson, Hong Sheng Cheng, Fransiskus Xaverius Ivan, Si Chen, Adrian E. Z. Kang, Randy Foo, Akshamal M. Gamage, Pei Yee Tiew, Mariko Siyue Koh, Ken Cheah Hooi Lee, Kristy Nichol, Prabuddha S. Pathinayake, Yik Lung Chan, Tsin Wen Yeo, Brian G. Oliver, Peter A. B. Wark, Linbo Liu, Nguan Soon Tan, Lin-Fa Wang, and Sanjay H. Chotirmall
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Science - Abstract
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory respiratory disease characterized by airflow limitation and infective exacerbations. Here, Chan et al. report the generation of nasopharyngeal and bronchial COPD organoids derived from adult stem cells and employ them in the study of host-pathogen interactions, including SARS-CoV-2 and Pseudomonas aeruginosa.
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- 2022
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10. Synergistic efficacy of PI3Kδ inhibitor with anti-PD-1 mAbs in immune-humanized PDX model of endocrine resistance hormone receptor-positive advanced breast cancer
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Yingjue Li, Yiwen Li, Yu Yang, Yuwei Deng, Xiangdong Ni, Bochen Zhao, Zhaoqi Yan, Wen He, Yixin Li, Shuhui Li, Linbo Liu, and Dan Lu
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Breast cancer (BC) ,Patient-derived xenograft ,Immune checkpoint inhibitors ,PI3Kδ inhibitor ,Endocrine therapy resistance ,Humanized mice ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Purpose: Endocrine resistance hormone receptor-positive (HR+) advanced breast cancer (ABC) is generally insensitive to immunecheckpoint inhibitors (ICIs). This study sought to determine whether PI3Kδ inhibitor could enhance the sensitivity of endocrine resistance HR + advanced BC to ICIs by reducing immune evasion. Methods: Patient-derived HR + ABC xenografts were implanted into immune-humanized NSG mice and subsequently treated with YY20394 (PI3Kδ inhibitor) and camrelizumab. The mice were monitored for tumor progression, biochemical blood indicators, and peripheral blood T-cell subsets. The xenografted tumors were collected at the end of the treatment cycle and subjected to HE staining, immunohistochemistry and protein phosphorylation analysis. Besides, the xenografted tumors were also used to isolate primary breast cancer cells (BCCs) and regulatory T-cells (Tregs), which were subsequently used to evaluate drug sensitivity in vitro. Results: The humanized PDX model showed a favorable initial treatment response to camrelizumab combined with YY20394 and manageable toxicity. YY20394 plus camrelizumab showed a strong inhibitory effect on HR + BC in vivo mediated by suppression of Treg activity and an increased proportion of CD8+ T cells. Mice bearing tumors treated with YY20394 and camrelizumab had less invasion, mitotic figures, and ki67 expression, while having higher IL-12 expression compared with other groups. Mechanistically, YY20394 only effectively inhibited the PI3K pathway and proliferation activity in Tregs but not in BCCs. Conclusion: Our study suggests PI3Kδ inhibitor could the enhance the efficacy of ICIs in HR + BC PDX models by combating immune suppression and provides a feasible approach that may overcome the resistance of ICIs in HR + BC patients.
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- 2023
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11. The prevalence of lower eyelid epiblepharon and its association with refractive errors in Chinese preschool children: a cross-sectional study
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Deyi Zhuo, Si Chen, Xiaofang Ren, Bingsong Wang, Linbo Liu, and Lin Xiao
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Lower eyelid epiblepharon ,Astigmatism ,Myopia ,Refractive error ,Preschool children ,Ophthalmology ,RE1-994 - Abstract
Abstract Background To assess the prevalence and demographics of lower eyelid epiblepharon in Chinese preschool children and to evaluate its association with refractive errors. Methods In this population-based, cross-sectional study, a total of 3170 children aged 3 to 6 years from Beijing, China underwent examinations including weight, height, cycloplegic autorefraction and slit-lamp examination of external eyes. The prevalence of lower eyelid epiblepharon in preschool children was evaluated and its association with age, sex, body mass index (BMI), and refractive errors was analyzed using logistic regression analysis. Results The prevalence of lower eyelid epiblepharon was 26.2%, which decreased with age, with prevalence in 3-, 4-, 5-, and 6-year-olds of 30.6, 28.0, 15.0, and 14.3%, respectively. Boys had a higher risk of having epiblepharon than girls (OR = 1.41; 95%CI, (1.20–1.66)) and no significant correlation was detected between BMI and epiblepharon after adjusting for age and sex (p = 0.062). Epiblepharon was significantly associated with a higher risk of refractive errors, including astigmatism (OR = 3.41; 95% CI, (2.68–4.33)), myopia (OR = 3.55; 95% CI, (1.86–6.76)), and hyperopia (OR = 1.53; 95% CI, (1.18–1.99)). Conclusions There is a high prevalence of lower eyelid epiblepharon in Chinese preschool children, particularly among boys and younger children. Preschoolers with lower eyelid epiblepharon are subject to a higher risk of developing astigmatism, myopia, and hyperopia, than those without. Increased attention should be paid to this eyelid abnormality in the preschool population.
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- 2021
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12. Aberration Mitigation in High-Resolution Optical Coherence Tomography Implementing Elliptical Beam Design
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Jinhan Li, Jun Xie, and Linbo Liu
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Interferometry ,optical coherence tomography ,spectroscopy ,Applied optics. Photonics ,TA1501-1820 ,Optics. Light ,QC350-467 - Abstract
We report an elliptical beam design for aberration mitigation in high-resolution optical coherence tomography (OCT). We polished a large angle on the fiber terminal facet in the sample arm to make a non-rotational symmetric beam with different numerical apertures (NA) for the two axes vertical to the optical axis. By sacrificing the resolution in the out-of-plane transverse direction, the elliptical beam mitigated the aberration introduced by the focusing optics in the OCT system. The elliptical beam with a doubled NA in the in-plane transverse direction promoted the axial field-of-view (FOV) by about 50% and increased the signal back-coupling efficiency by about 25%. We verified the feasibility of the design by imaging the USAF 1951 resolution chart, swine cornea ex vivo, and human skin in vivo. Results show that the proposed method relieves aberration-related problems in high-resolution OCT.
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- 2021
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13. Inspection of Intraocular Lens With Dual-Side View Optical Coherence Tomography
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Qian Wu, Xiwen Wang, Linbo Liu, and Jianhua Mo
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Optical coherence tomography ,dual-side view ,intraocular lens ,inspection ,in vitro measurement ,Applied optics. Photonics ,TA1501-1820 ,Optics. Light ,QC350-467 - Abstract
Intraocular lens (IOL) is widely used for cataract treatment. Its optical properties are crucial to obtain a good treatment efficacy and thus need to be evaluated and controlled. In this study, we propose a novel method based on optical coherence tomography (OCT) for noncontact and accurate in vitro measurement of thickness, refractive index and dioptric power of IOL implants. The OCT setup is specially designed to create two sampling optics, called dual-side view OCT (DSV-OCT), which allows for imaging IOL from the two opposite sides simultaneously in single OCT volume scanning. This can produce a three-dimensional surface contour without suffering image distortions due to the refraction of the curved surface. Then, the thickness and surface curvature can be easily computed from the surface contours. In addition, DSV-OCT is able to measure the refractive index. Three IOLs with different dioptric powers (5D, 20D and 28D) were chosen to evaluate this method. The results show that this method is capable to provide a comprehensive and accurate evaluation of IOLs from the aspects of thickness, refractive index and dioptric power, and hence can be potentially used as a quality assurance tool by IOL manufacturers.
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- 2021
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14. Design of a Broadband Fiber Optic Mode Coupler for Multimode Optical Coherence Tomography
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Dora Juan Juan Hu, Linbo Liu, Hui Dong, and Hailiang Zhang
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multimode optical coherence tomography ,few-mode fiber (FMF) ,broadband fiber optic mode coupler ,Applied optics. Photonics ,TA1501-1820 - Abstract
In this paper, we propose an optical fiber-based broadband mode coupler for multimode optical coherence tomography (OCT) in the O-band (1.26–1.36 μm). The proposed device uses a tapered few-mode fiber (FMF) to lower the effective mode index of the selected higher-order mode, which can be phase matched to the fundamental mode of the single-mode fiber (SMF). The tapered FMF and the SMF are side polished to reduce the core-to-core separation to achieve efficient mode coupling. Key design parameters such as the tapering ratio of the FMF, FMF core to SMF core separation, coupler length, and coupling ratio in the O-band are studied thoroughly. Higher-order modes of the FMF will be effectively coupled from the fundamental mode of SMF in the sample arm of the multimode OCT system. The reflected signals of the higher-order modes from the sample will be separated into several single-mode signals using the same fiber device before interfering with the reference light, which was not possible before. The proposed fiber device will be a key component to efficiently achieve multimode OCT operation with better signal collection efficiency and improved penetration depth for deep tissue imaging.
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- 2023
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15. Strain Sensor-Inserted Microchannel for Gas Viscosity Measurement
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Kota Shiba, Linbo Liu, and Guangming Li
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viscosity ,gas ,microchannel ,strain ,sensor ,PDMS ,Biotechnology ,TP248.13-248.65 - Abstract
Quantifying the viscosity of a gas is of great importance in determining its properties and can even be used to identify what the gas is. While many techniques exist for measuring the viscosities of gases, it is still challenging to probe gases with a simple, robust setup that will be useful for practical applications. We introduce a facile approach to estimating gas viscosity using a strain gauge inserted in a straight microchannel with a height smaller than that of the gauge. Using a constrained geometry for the strain gauge, in which part of the gauge deforms the channel to generate initial gauge strain that can be transduced into pressure, the pressure change induced via fluid flow was measured. The change was found to linearly correlate with fluid viscosity, allowing estimation of the viscosities of gases with a simple device.
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- 2023
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16. Step emulsification: high-throughput production of monodisperse droplets
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Linbo Liu, Nan Xiang, Zhonghua Ni, Xing Huang, Juanjuan Zheng, Yunhua Wang, and Xingcai Zhang
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high throughput ,microchannel arrays ,microfluidics ,monodisperse droplets ,spontaneous transformation ,step emulsification ,Biology (General) ,QH301-705.5 - Published
- 2020
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17. Feasibility evaluation of micro-optical coherence tomography (μOCT) for rapid brain tumor type and grade discriminations: μOCT images versus pathology
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Xiaojun Yu, Chi Hu, Wenfei Zhang, Jie Zhou, Qianshan Ding, M. T. Sadiq, Zeming Fan, Zhaohui Yuan, and Linbo Liu
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Glioma ,Meningioma ,Micro-OCT ,Patholgoy ,Tumor discrimination ,Medical technology ,R855-855.5 - Abstract
Abstract Background Precise identification, discrimination and assessment of central nervous system (CNS) tumors is of critical importance to brain neoplasm treatment. Due to the complexity and limited resolutions of the existing diagnostic tools, however, it is difficult to identify the tumors and their boundaries precisely in clinical practice, and thus, the conventional way of brain neoplasm treatment relies mainly on the experiences of neurosurgeons to make resection decisions in the surgery process. The purpose of this study is to explore the potential of Micro-optical coherence tomography (μOCT) as an intraoperative diagnostic imaging tool for identifying and discriminating glioma and meningioma with their microstructure imaging ex vivo, which thus may help neurosurgeons to perform precise surgery with low costs and reduced burdens. Methods Fresh glioma and meningioma samples were resected from patients, and then slices of such samples were excised and imaged instantly ex vivo with a lab-built μOCT, which achieves a spatial resolution of ~ 2.0 μm (μm). The acquired optical coherence tomography (OCT) images were pathologically evaluated and compared to their corresponding histology for both tumor type and tumor grade discriminations in different cases. Results By using the lab-built μOCT, both the cross-sectional and en face images of glioma and meningioma were acquired ex vivo. Based upon the morphology results, both the glioma and meningioma types as well as the glioma grades were assessed and discriminated. Comparisons between OCT imaging results and histology showed that typical tissue microstructures of glioma and meningioma could be clearly identified and confirmed the type and grade discriminations with satisfactory accuracy. Conclusions μOCT could provide high-resolution three-dimensional (3D) imaging of the glioma and meningioma tissue microstructures rapidly ex vivo. μOCT imaging results could help discriminate both tumor types and grades, which illustrates the potential of μOCT as an intraoperative diagnostic imaging tool to help neurosurgeons perform their surgery precisely in tumor treatment process.
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- 2019
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18. AN EXPERIMENTAL STUDY ON PERFORMANCE OF SHAPE MEMORY ALLOY SUSPENSION PENDULUM DAMPING SYSTEM
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Ergang Xiong, Sheliang Wang, Tuanjie Fan, Linbo Liu, Kun Zu, and Yanghong Xi
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superelasticity ,sma suspension pendulum damping system ,phase relation ,equivalent damping force ,Engineering (General). Civil engineering (General) ,TA1-2040 - Abstract
A systematic study is conducted on variation regularities for such properties of SMA wires with the diameter of wires, strain amplitude and loading cycles as the stress-strain curve, characteristic stresses, energy dissipation capacity, equivalent damping ratio. The results show: The diameter increase of SMA wires can degrade the mechanical properties of SMA wires; SMA wires can exhibit a good and stable hysteretic performance when the strain amplitude is 6% and the loading cycle is 15. Utilizing the superelasticity of SMA and combining the operating principle of the tuned mass damper, a new kind of SMA suspension pendulum damping system, which is easy to disassemble, was designed and fabricated with the trained SMA wires. Corresponding experiments were conducted to analyse the natural frequency of the damping system, phase relations between the mass vibrators and the controlled structure, variation regularity of the equivalent damping force with the mass vibrators and length of pendulum rod. The results indicate that phase relations between the mass vibrators and the controlled structure can desirably fall within 150°~180° when this damping system subjected to the sine waves and real earthquake waves. Meanwhile, the equivalent damping force increases significantly with the amplitude of external loads. In conclusion, this kind of damping system can provide a stable and efficient damping force and be simply applied to structural vibration control, thus to protect structures free from strong dynamic disasters.
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- 2019
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19. Geometry-Dependent Spectroscopic Contrast in Deep Tissues
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Xin Ge, Hongying Tang, Xianghong Wang, Xinyu Liu, Si Chen, Nanshuo Wang, Guangming Ni, Xiaojun Yu, Shufen Chen, Haitao Liang, En Bo, Lulu Wang, Cilwyn Shalitha Braganza, Chenjie Xu, Steven M. Rowe, Guillermo J. Tearney, and Linbo Liu
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Science - Abstract
Summary: Nano-structures of biological systems can produce diverse spectroscopic effects through interactions with broadband light. Although structured coloration at the surface has been extensively studied, natural spectroscopic contrasts in deep tissues are poorly understood, which may carry valuable information for evaluating the anatomy and function of biological systems. Here we investigated the spectroscopic characteristics of an important geometry in deep tissues at the nanometer scale: packed nano-cylinders, in the near-infrared window, numerically predicted and experimentally proved that transversely oriented and regularly arranged nano-cylinders could selectively backscatter light of the long wavelengths. Notably, we found that the spectroscopic contrast of nanoscale fibrous structures was sensitive to the pressure load, possibly owing to the changes in the orientation, the degree of alignment, and the spacing. To explore the underlying physical basis, we further developed an analytical model based on the radial distribution function in terms of their radius, refractive index, and spatial distribution. : Infrared Optics; Medical Imaging; Optical Imaging; Spectroscopy Subject Areas: Infrared Optics, Medical Imaging, Optical Imaging, Spectroscopy
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- 2019
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20. Optical Coherence Tomography With Gapped Spectrum
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Nanshuo Wang, Xinyu Liu, Xiaojun Yu, Si Chen, Shi Chen, and Linbo Liu
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Optical coherence tomography ,Applied optics. Photonics ,TA1501-1820 ,Optics. Light ,QC350-467 - Abstract
The axial resolution of optical coherence tomography (OCT) is determined by the spectral shape and bandwidth of the detected light, which are limited by the gaps in the wavelength range of illumination, transmission, and detection. In this paper, we demonstrate that the axial resolution deteriorated by gaps in OCT spectra can be restored by adopting the gapped amplitude and phase estimation (GAPES) method. GAPES estimates the missing parts between separated spectral bands and obtains the axial profile of tissue with reduced sidelobe artifacts compared to the gapped spectra and significantly improved axial resolution over the individual bands. This technique may make it possible to combine spectrally separated sources and detectors to improve axial resolution in OCT images.
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- 2019
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21. Nondestructive Measurement of Conformal Coating Thickness on Printed Circuit Board With Ultra-High Resolution Optical Coherence Tomography
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Xiao Shao, Xinjian Chen, Xiaojun Yu, Ya Hu, Linbo Liu, Fei Shi, Wei Shao, and Jianhua Mo
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Optical coherence tomography ,conformal coating ,thickness measurement ,image segmentation ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 - Abstract
Conformal coating (CC) is widely used to protect printed circuit board from corrosion, mold growth, and electrical failures. To ensure effective protection, the thickness of the CC layer needs to be well controlled. However, to date, the coating thickness is usually measured in a destructive way under microscopes. In this paper, we proposed to use optical coherence tomography (OCT) to measure the CC thickness nondestructively. Specifically, to obtain a good accuracy in thickness measurement, we constructed a spectral domain OCT with the ultra-high axial resolution to image the CC layer in three dimensions and developed an image segmentation algorithm to detect the CC layer from the OCT images. Finally, we evaluated the effectiveness of the proposed method by comparing it with the conventional method, and the results demonstrate that the measurement by our method is consistent with that by the microscope. This also indicates that OCT with high axial resolution can potentially be used to measure the CC thickness accurately and nondestructively.
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- 2019
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22. Imaging Cellular Structures of Atherosclerotic Coronary Arteries Using Circumferentially Scanning Micro-Optical Coherence Tomography Fiber Probe Ex Vivo
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Yuemei Luo, En Bo, Haitao Liang, Xianghong Wang, Xiaojun Yu, Dongyao Cui, Xin Ge, Jianhua Mo, and Linbo Liu
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Optical fiber devices ,optical coherence tomography ,fiber optics imaging ,intravascular imaging ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 - Abstract
Development and progression of coronary atherosclerotic lesions is mediated by a number of cellular components that are not readily visualized using the current clinical investigation tools. Visualizing these cellular components in situ and in vivo may allow early detection of the vulnerable plaques, with implications for coronary artery disease therapy and for the prevention of acute myocardial infarction. In this paper, we have developed a fiber-optic micro-optical coherence tomography (μ OCT) probe for intravascular use. We conducted ex vivo imaging experiments in normal swine aorta and human atherosclerotic coronary arteries and demonstrated that the fiber-probe-based μ OCT could delineate not only the layered structures of arterial wall but also the cellular-level anatomical structures of atherosclerotic plaques, including foam cells and smooth muscle cells. These results demonstrate the feasibility of intravascular μ OCT imaging.
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- 2018
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23. Pixel-Reassigned Spectral-Domain Optical Coherence Tomography
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En Bo, Lulu Wang, Jun Xie, Xin Ge, and Linbo Liu
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Optical coherence tomography (OCT) ,coherent imaging ,biophotonics instrumentation ,medical photonics instrumentation ,Applied optics. Photonics ,TA1501-1820 ,Optics. Light ,QC350-467 - Abstract
A novel method of pixel reassignment (PRA) is proposed to achieve transverse superresolution in the confocal microscopy. Inspired by it, for the first time, we report a pixel-reassigned spectral-domain optical coherence tomography (OCT) with ~1.5 times transverse resolution improvement both in numerical simulations and imaging experiments. PRA is implemented by transversely shifting the detection fiber from the on-axis position to five off-axis positions, capturing cross-sectional images at each shifting step of the detection fiber and digitally reassigning them together to give a sharper image with moderately extended depth of focus and enhanced intensity. So, we believe that the PRA technique will improve the imaging performance and be beneficial to the development of the OCT community.
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- 2018
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24. Structure–activity relationship investigation of tertiary amine derivatives of cinnamic acid as acetylcholinesterase and butyrylcholinesterase inhibitors: compared with that of phenylpropionic acid, sorbic acid and hexanoic acid
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Xiaohui Gao, Jingjing Tang, Haoran Liu, Linbo Liu, Lu Kang, and Wen Chen
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Cinnamic acid ,tertiary amine ,AChE inhibitors ,benzene ring ,double bond ,Therapeutics. Pharmacology ,RM1-950 - Abstract
In the present investigation, 48 new tertiary amine derivatives of cinnamic acid, phenylpropionic acid, sorbic acid and hexanoic acid (4d–6g, 10d–12g, 16d–18g and 22d–24g) were designed, synthesized and evaluated for the effect on AChE and BChE in vitro. The results revealed that the alteration of aminoalkyl types and substituted positions markedly influences the effects in inhibiting AChE. Almost of all cinnamic acid derivatives had the most potent inhibitory activity than that of other acid derivatives with the same aminoalkyl side chain. Unsaturated bond and benzene ring in cinnamic acid scaffold seems important for the inhibitory activity against AChE. Among them, compound 6g revealed the most potent AChE inhibitory activity (IC50 value: 3.64 µmol/L) and highest selectivity over BChE (ratio: 28.6). Enzyme kinetic study showed that it present a mixed-type inhibition against AChE. The molecular docking study suggested that it can bind with the catalytic site and peripheral site of AChE.
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- 2018
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25. Visualizing Micro-anatomical Structures of the Posterior Cornea with Micro-optical Coherence Tomography
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Si Chen, Xinyu Liu, Nanshuo Wang, Xianghong Wang, Qiaozhou Xiong, En Bo, Xiaojun Yu, Shufen Chen, and Linbo Liu
- Subjects
Medicine ,Science - Abstract
Abstract Diagnosis of corneal disease and challenges in corneal transplantation require comprehensive understanding of corneal anatomy, particularly that of the posterior cornea. Micro-optical coherence tomography (µOCT) is a potentially suitable tool to meet this need, owing to its ultrahigh isotropic spatial resolution, high image acquisition rate and depth priority scanning mode. In this study, we explored the ability of µOCT to visualize micro-anatomical structures of the posterior cornea ex vivo and in vivo using small and large animals. µOCT clearly delineated cornea layers and revealed micro-anatomical structures, including not only polygonal endothelial cells, stellate keratocytes, collagen fibres and corneal nerve fibres but also new structures such as the dome-shaped basolateral side of endothelial cells and lattice structures at the interface between endothelium and Descemet’s membrane. Based on these observations, a short post-harvest longitudinal study was conducted on rat cornea to test the feasibility of using µOCT to monitor the quality of endothelial cells. This study successfully reveals a series of morphological features and pathological changes in the posterior cornea at the cellular level in situ and in real time with µOCT. These findings enrich knowledge of corneal anatomy and suggest that µOCT may be a promising imaging tool in corneal transplantation.
- Published
- 2017
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26. Understanding optical reflectance contrast for real‐time characterization of epithelial precursor lesions
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Si Chen, Xin Ge, Xinyu Liu, Qianshan Ding, Nanshuo Wang, Xianghong Wang, Shufen Chen, Haitao Liang, Yunchao Deng, Qiaozhou Xiong, Guangming Ni, En Bo, Chenjie Xu, Honggang Yu, and Linbo Liu
- Subjects
epithelial cancer ,keratin filament ,mucin granule ,optical biopsy ,optical coherence tomography ,optical reflectance contrast ,Chemical engineering ,TP155-156 ,Biotechnology ,TP248.13-248.65 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract Detecting early‐stage epithelial cancers and their precursor lesions are challenging as lesions could be subtle and focally or heterogeneously distributed over large mucosal areas. Optical coherence tomography (OCT) that enables wide‐field imaging of subsurface microstructures in vivo is a promising screening tool for epithelial diseases. However, its diagnostic capability has not been fully appreciated since the optical reflectance contrast is poorly understood. We investigated the back‐scattered intensities from clustered or packed nanometer scale intracellular scatterers using finite‐difference time‐domain method and 1‐μm resolution form of OCT, and uncovered that there existed correlations between the reflectance contrasts and the ultrastructural clustering or packing states of these scatterers, which allows us to interpret the physiological state of the cells. Specifically, both polarized goblet cells and foveolar cells exhibited asymmetric reflectance contrast, but they could be differentiated by the optical intensity of the mucin cup due to the different ultrastructural make‐ups of the mucin granules; keratinocytes could demonstrate varied cytoplasmic intensity and their cytoplasmic contrast was closely correlated with the packing state of keratin filaments. Further preliminary study demonstrated that these new understandings of OCT image contrast enables the characterization of precancerous lesions, which could complement the current morphology‐based criteria in realizing “virtual histology” and would have a profound impact for the screening and surveillance of epithelial cancers.
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- 2019
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27. Prediction of the engendering mechanism and specific genes of primary melanoma by bioinformatics analysis
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Lei Wu, Bin Dong, Fang Zhang, Yonglin Li, and Linbo Liu
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differentially expressed gene ,melanoma ,protein–protein interaction network ,transcription factor ,tumor-associated gene ,Dermatology ,RL1-803 - Abstract
Objective: Our aim was to explore the engendering mechanism and gene targets for melanoma. Methods: The microarray data of GSE46517 were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between primary melanoma samples and normal controls were analyzed using the GEO2R online tool. The screened DEGs were mapped to a protein–protein interaction network based on the Search Tool for the Retrieval of Interacting Genes database. The functions and pathways involved with DEGs were analyzed using the Database for Annotation Visualization and Integrated Discovery software) online tools. Then, the DEGs were further annotated via the TRANSFAC, Tumor-Suppressor Gene, and Tumor-Associated Gene databases. Results: A total of 1095 DEGs including 511 upregulated genes and 584 down-regulated ones were screened out. The nodes of CCL5, ISG15, CDKN2A, EGFR, and ERBB2 showed a high connectivity degree in protein–protein interaction networks and were mainly enriched in Biological Process GO terms such as the regulation of catalytic activity and cell adhesion, as well as the pathways of cytochrome P450. The DEGs were classified into 31 transcription factors and 43 downregulated tumor associated genes. Conclusion: Catalytic activity, cell adhesion, and the cytochrome P450 associated pathways are dysregulated in the melanoma formation. The significant nodes such as ISG15, IRF4, ERBB2 and EGFP may be potential targets for primary melanoma treatment.
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- 2016
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28. Microfluidic Production of Autofluorescent BSA Hydrogel Microspheres and Their Sequential Trapping for Fluorescence-Based On-Chip Permanganate Sensing
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Linbo Liu, Guangming Li, Nan Xiang, Xing Huang, and Kota Shiba
- Subjects
droplet-based microfluidics ,hydrodynamic trapping ,BSA microspheres ,autofluorescence ,on-chip sensing ,Chemical technology ,TP1-1185 - Abstract
Microfabrication technologies have extensively advanced over the past decades, realizing a variety of well-designed compact devices for material synthesis, separation, analysis, monitoring, sensing, and so on. The performance of such devices has been undoubtedly improved, while it is still challenging to build up a platform by rationally combining multiple processes toward practical demands which become more diverse and complicated. Here, we present a simple and effective microfluidic system to produce and immobilize a well-defined functional material for on-chip permanganate (MnO4−) sensing. A droplet-based microfluidic approach that can continuously produce monodispersed droplets in a water-in-oil system is employed to prepare highly uniform microspheres (average size: 102 μm, coefficient of variation: 3.7%) composed of bovine serum albumin (BSA) hydrogel with autofluorescence properties in the presence of glutaraldehyde (GA). Each BSA hydrogel microsphere is subsequently immobilized in a microchannel with a hydrodynamic trapping structure to serve as an independent fluorescence unit. Various anions such as Cl−, NO3−, PO43−, Br−, BrO3−, ClO4−, SCN−, HCO3−, and MnO4− are individually flowed into the microchannel, resulting in significant fluorescence quenching only in the case of MnO4−. Linear correlation is confirmed at an MnO4− concentration from 20 to 80 μM, and a limit of detection is estimated to be 1.7 μM. Furthermore, we demonstrate the simultaneous immobilization of two kinds of different microspheres in parallel microchannels, pure BSA hydrogel microspheres and BSA hydrogel microspheres containing rhodamine B molecules, making it possible to acquire two fluorescence signals (green and yellow). The present microfluidics-based combined approach will be useful to record a fingerprint of complicated samples for sensing/identification purposes by flexibly designing the size and composition of the BSA hydrogel microspheres, immobilizing them in a desired manner and obtaining a specific pattern.
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- 2020
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29. Toward High-Speed Imaging of Cellular Structures in Rat Colon Using Micro-optical Coherence Tomography
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Xiaojun Yu, Yuemei Luo, Xinyu Liu, Si Chen, Xianghong Wang, Shi Chen, and Linbo Liu
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Optical coherence tomography ,biophotonics instrumentation ,coherence imaging ,scanning microscopy ,medical photonics instrumentation ,Applied optics. Photonics ,TA1501-1820 ,Optics. Light ,QC350-467 - Abstract
The mucosal microanatomy of the large intestine is characterized by the presence of crypts of Lieberkühn, which is associated predominantly with goblet cells. Such cellular-level intestinal microstructures undergo morphological changes during the progression of bowel diseases, such as colon cancer or ulcerative colitis. As an indicator of gastric cancers, intestinal metaplasia in the large intestine is characterized by the appearance of goblet cells in gastric epithelium, and therefore, visualization of intestinal microstructure changes in cross-sectional view, particularly in vivo, in a high-speed fashion would assist early disease diagnosis and its treatment. In this paper, we investigated the capability of micro-optical coherence tomography (μOCT) for high-speed cellular-level crypt and goblet cell structures imaging ex vivo and in vivo . The adopted μOCT system achieved a resolution of 2.0 μm in both the lateral and axial directions in air. Ex vivo and video-rate in vivo images acquired in 3-D at respective imaging rates of 20 and 60 frames/s are presented and compared with the histology images. Imaging results show that the detailed microstructures, such as the crypt lumen and the goblet cells, could be clearly identified and are also comparable with those in histology images. Such comparisons also indicate that high-resolution μOCT could be a powerful tool to perform “optical biopsy” in colorectal tissue. This is the first work, to the best of our knowledge, on cellular-level structure imaging in intestinal mucosa using spectral-domain OCT.
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- 2016
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30. Modeling of Mechanical Stress Exerted by Cholesterol Crystallization on Atherosclerotic Plaques.
- Author
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Yuemei Luo, Dongyao Cui, Xiaojun Yu, Si Chen, Xinyu Liu, Hongying Tang, Xianghong Wang, and Linbo Liu
- Subjects
Medicine ,Science - Abstract
Plaque rupture is the critical cause of cardiovascular thrombosis, but the detailed mechanisms are not fully understood. Recent studies have found abundant cholesterol crystals in ruptured plaques, and it has been proposed that the rapid expansion of cholesterol crystals in a limited space during crystallization may contribute to plaque rupture. To evaluate the effect of cholesterol crystal growth on atherosclerotic plaques, we modeled the expansion of cholesterol crystals during the crystallization process in the necrotic core and estimated the stress on the thin cap with different arrangements of cholesterol crystals. We developed a two-dimensional finite element method model of atherosclerotic plaques containing expanding cholesterol crystals and investigated the effect of the magnitude and distribution of crystallization on the peak circumferential stress born by the cap. Using micro-optical coherence tomography (μOCT), we extracted the cross-sectional geometric information of cholesterol crystals in human atherosclerotic aorta tissue ex vivo and applied the information to the model. The results demonstrate that (1) the peak circumference stress is proportionally dependent on the cholesterol crystal growth; (2) cholesterol crystals at the cap shoulder impose the highest peak circumference stress; and (3) spatial distributions of cholesterol crystals have a significant impact on the peak circumference stress: evenly distributed cholesterol crystals exert less peak circumferential stress on the cap than concentrated crystals.
- Published
- 2016
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31. Feasibility of the assessment of cholesterol crystals in human macrophages using micro optical coherence tomography.
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Manabu Kashiwagi, Linbo Liu, Kengyeh K Chu, Chen-Hsin Sun, Atsushi Tanaka, Joseph A Gardecki, and Guillermo J Tearney
- Subjects
Medicine ,Science - Abstract
The presence of cholesterol crystals is a hallmark of atherosclerosis, but until recently, such crystals have been considered to be passive components of necrotic plaque cores. Recent studies have demonstrated that phagocytosis of cholesterol crystals by macrophages may actively precipitate plaque progression via an inflammatory pathway, emphasizing the need for methods to study the interaction between macrophages and crystalline cholesterol. In this study, we demonstrate the feasibility of detecting cholesterol in macrophages in situ using Micro-Optical Coherence Tomography (µOCT), an imaging modality we have recently developed with 1-µm resolution. Macrophages containing cholesterol crystals frequently demonstrated highly scattering constituents in their cytoplasm on µOCT imaging, and µOCT was able to evaluate cholesterol crystals in cultured macrophage cells. Our results suggest that µOCT may be useful for the detection and characterization of inflammatory activity associated with cholesterol crystals in the coronary artery.
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- 2014
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32. Method for quantitative study of airway functional microanatomy using micro-optical coherence tomography.
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Linbo Liu, Kengyeh K Chu, Grace H Houser, Bradford J Diephuis, Yao Li, Eric J Wilsterman, Suresh Shastry, Gregory Dierksen, Susan E Birket, Marina Mazur, Suzanne Byan-Parker, William E Grizzle, Eric J Sorscher, Steven M Rowe, and Guillermo J Tearney
- Subjects
Medicine ,Science - Abstract
We demonstrate the use of a high resolution form of optical coherence tomography, termed micro-OCT (μOCT), for investigating the functional microanatomy of airway epithelia. μOCT captures several key parameters governing the function of the airway surface (airway surface liquid depth, periciliary liquid depth, ciliary function including beat frequency, and mucociliary transport rate) from the same series of images and without exogenous particles or labels, enabling non-invasive study of dynamic phenomena. Additionally, the high resolution of μOCT reveals distinguishable phases of the ciliary stroke pattern and glandular extrusion. Images and functional measurements from primary human bronchial epithelial cell cultures and excised tissue are presented and compared with measurements using existing gold standard methods. Active secretion from mucus glands in tissue, a key parameter of epithelial function, was also observed and quantified.
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- 2013
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33. Synthesis of Poly(L-lactide) via Solvothermal Method
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Ling Fang, Rongrong Qi, Linbo Liu, Gongwen Juan, and Suangwu Huang
- Subjects
Chemical technology ,TP1-1185 - Abstract
Poly(L-lactide) was obtained from the ring-opening polymerization of L-lactide through a solvothermal process. Tin (II) chloride (SnC12) was used as the catalyst for the polymerization reaction. The focus of this paper was on the effect of solvents, catalyst usage, temperature, time, and antioxidants on the ring-opening reaction in the solvothermal synthesis. Ubbelohde viscometer, FTIR, GPC, and DSC were used to characterize the products. It is found that the optimal reaction condition for the highest molecular weight of PLA is at 160∘C for 10 hour with 0.4% SnCl2 in 10 mL toluene as solvent, and the high crystallinity can be obtained. The addition of antioxidant prior to the polymerization is conducive to obtaining high molecular weight and augment Tm, Tc and Xc values of PLA.
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- 2009
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34. RETRACTED ARTICLE: Circ_0002770, acting as a competitive endogenous RNA, promotes proliferation and invasion by targeting miR-331-3p in melanoma
- Author
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Qian, Peng, Linbo, Liu, Xiaomei, Zhai, and Hui, Pei
- Published
- 2020
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35. Efficacy and Safety of Botulinum Toxin Type A in the Treatment of Benign Parotid Hypertrophy: A Prospective Study
- Author
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Zong, Chen, Zhiyou, Chen, Wenhui, Liu, Zhiru, Wei, Ran, Pang, Xu, Cheng, Shuqi, Wang, Shengjun, Chen, Linbo, Liu, and Guangshuai, Li
- Subjects
Neuromuscular Agents ,Humans ,Parotid Gland ,Surgery ,Prospective Studies ,Hypertrophy ,Botulinum Toxins, Type A - Abstract
Benign parotid hypertrophy makes the earlobe area appear swollen and weakens the lateral facial contour and aesthetics. Efficacious treatment for benign parotid hypertrophy is not available. The authors evaluated the efficacy and safety of botulinum toxin type A for benign parotid hypertrophy treatment.Thirty-six participants with benign parotid hypertrophy were enrolled and treated with botulinum toxin type A injection. After 6 months of follow-up, changes in the thickness and length of the superficial lobe of the parotid gland were assessed. Analyses of patient subgroups and image analyses were also undertaken to assess improvement.Thirty-three participants completed this study. Superficial lobe of the parotid gland thickness was reduced significantly after botulinum toxin type A injection, but the longitudinal diameter of the parotid gland was not changed significantly ( p0.001 and p = 0.146, respectively). Subgroup analyses showed that the degree of parotid gland hypertrophy affected treatment efficacy and degree of improvement, but age and sex did not ( p0.001, p = 0.137, and p = 0.138, respectively). Image analyses showed improvement in the facial contour ( p0.05). Serious adverse reactions or complications were not observed.Botulinum toxin type A can be used to treat benign parotid hypertrophy, reduce parotid gland volume, and improve the facial contour.Therapeutic, IV.
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- 2022
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36. The Mechanical Properties and Microstructure of Nanostructured Cu with a Flexible Random Distribution of Multimodal Grain Size Prepared by a Combination of Electrodeposition and Recrystallization Annealing
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Xixun Shen, Linbo Liu, Qunjie Xu, Hong Yun, Chengwei Deng, and Tao Wang
- Subjects
Materials science ,Mechanics of Materials ,Annealing (metallurgy) ,Mechanical Engineering ,Ultimate tensile strength ,Hardening (metallurgy) ,Recrystallization (metallurgy) ,General Materials Science ,Strain hardening exponent ,Composite material ,Deformation (engineering) ,Microstructure ,Grain size - Abstract
A bulk nanostructured (NS) Cu with a flexible random distribution of multimodal grain size ranging from 1.12 μm to 30 nm was fabricated here by annealing a pre-designed heterogeneous layered structure Cu template fabricated by electrodeposition where the small grains with average grain size of about 40 nm and a large grain size with near micron scale distribute alternately according to the layer thickness ratio of about 4:1 along the deposition direction. Such a heterogeneous NS Cu exhibits a remarkable large strain hardening ability in tensile deformation, which results in a superior combination of high ductility of elongation to failure of near 40% and moderated strength of yield strength of about 470 MPa. Several strengthening effects brought by such a heterostructure, including producing more effective dislocation activity, the inhibition of local plastic flow and the release of local stress concentration, have been suggested to contribute to a more durable strain hardening ability and excellent mechanical properties of NS Cu. In addition, the morphology of fracture and deformation surface is captured to analyze the difference in the mechanical behavior of the NS Cu with random distribution of multimodal grain size by comparing with other structure Cu.
- Published
- 2021
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37. Human Adipose Tissue Cryopreservation: Impact of Different Calf Serum Concentrations on Tissue Viability
- Author
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Pu Wang, Luosha Gu, Jinsong Gu, Linbo Liu, and Yin Sun
- Subjects
Cryopreservation ,Tissue Survival ,Cryoprotectant ,Cell Survival ,Chemistry ,Dimethyl sulfoxide ,Mice, Nude ,Medicine (miscellaneous) ,Adipose tissue ,Cell Biology ,General Medicine ,General Biochemistry, Genetics and Molecular Biology ,Andrology ,Transplantation ,Mice ,chemistry.chemical_compound ,Cryoprotective Agents ,Adipose Tissue ,Animals ,Humans ,Dimethyl Sulfoxide ,Viability assay ,Stem cell ,Fetal bovine serum - Abstract
Adipose tissue, which is harvested in large quantities during liposuction, has no blood supply and becomes necrotic within a few hours, if not immediately transplanted. Cryopreservation of adipose tissue allows these samples to be stored and used in diverse fundamental experiments, especially in fat-grafting animal tests that could provide a theoretical basis for clinical applications. Traditionally, fetal bovine serum (FBS) has been added as a cryoprotectant (CPA) to maintain the maximum viability of different tissues after freezing and thawing. Calf serum (CS) comes from the same species as FBS but is more economical compared with FBS-containing medium. The optimal concentration of CS in CPA for banking adipose tissue has not been studied. Here, we studied the cell survival rate, cell viability, tissue structural integrity, number of adipose-derived stem cells and blood vessels, and survival after transplantation into nude mice via ultrastructural evaluation of adipose tissue cryopreserved for 6 months in condition A (60% CS, 15% dimethyl sulfoxide [DMSO], 25% Dulbecco's modified Eagle's medium [DMEM]) and condition B (30% CS, 15% DMSO, 55% DMEM). Our results indicate that CS in addition to CPA results in adequate preservation of adipose tissue, especially when a higher concentration of CS (60%) is used in the CPA.
- Published
- 2021
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38. LncRNA H19 promotes keloid formation through targeting the miR-769-5p/EIF3A pathway
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Nan Sun, Guangshuai Li, Lingang Xu, and Linbo Liu
- Subjects
0301 basic medicine ,Eukaryotic Initiation Factor-3 ,Clinical Biochemistry ,Apoptosis ,Extracellular matrix ,03 medical and health sciences ,0302 clinical medicine ,Keloid ,Cell Movement ,Cell Line, Tumor ,Eukaryotic initiation factor ,microRNA ,medicine ,Humans ,Neoplasm Invasiveness ,Gene Silencing ,RNA, Small Interfering ,skin and connective tissue diseases ,Molecular Biology ,Inhibitory effect ,Cell Proliferation ,Gene knockdown ,Chemistry ,Gene Expression Profiling ,Cell Biology ,General Medicine ,Fibroblasts ,medicine.disease ,female genital diseases and pregnancy complications ,Extracellular Matrix ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Keloid formation ,030220 oncology & carcinogenesis ,embryonic structures ,Cancer research ,RNA, Long Noncoding - Abstract
Keloid is a skin disease characterized by fibrous hyperplasia, which is often difficult to cure. Long non-coding RNAs (lncRNAs) have been shown to be associated with the development of many diseases. However, the role and mechanism of lncRNA H19 in keloid has been less studied. Our study found that lncRNA H19 expression was increased in keloid tissues and fibroblasts. Besides, H19 knockdown hindered the proliferation, migration, invasion, extracellular matrix (ECM) deposition, and enhanced the apoptosis of keloid fibroblasts. Further experiments showed that microRNA (miR)-769-5p could be sponged by H19, and its knockdown reversed the suppression effect of H19 knockdown on keloid formation. Eukaryotic initiation factor 3A (EIF3A) was found to be a target of miR-769-5p, and its overexpression inverted the inhibition effect of miR-769-5p overexpression on keloid formation. Moreover, the expression of EIF3A was regulated by H19 and miR-769-5p in keloid fibroblasts. Collectively, LncRNA H19 might play an active role in keloid formation, which might provide a new target for the treatment of keloid.
- Published
- 2021
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39. Artificial intelligence-powered microfluidics for nanomedicine and materials synthesis
- Author
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Xingcai Zhang, Yunhua Wang, Junfeng Liu, Xiwen Jiang, Zhongbin Xu, Mingcheng Bi, and Linbo Liu
- Subjects
Emerging technologies ,business.industry ,Computer science ,Deep learning ,Scale (chemistry) ,Microfluidics ,Machine Learning ,Nanomedicine ,Artificial Intelligence ,General Materials Science ,Artificial intelligence ,business ,Material synthesis - Abstract
Artificial intelligence (AI) is an emerging technology with great potential, and its robust calculation and analysis capabilities are unmatched by traditional calculation tools. With the promotion of deep learning and open-source platforms, the threshold of AI has also become lower. Combining artificial intelligence with traditional fields to create new fields of high research and application value has become a trend. AI has been involved in many disciplines, such as medicine, materials, energy, and economics. The development of AI requires the support of many kinds of data, and microfluidic systems can often mine object data on a large scale to support AI. Due to the excellent synergy between the two technologies, excellent research results have emerged in many fields. In this review, we briefly review AI and microfluidics and introduce some applications of their combination, mainly in nanomedicine and material synthesis. Finally, we discuss the development trend of the combination of the two technologies.
- Published
- 2021
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40. CGNet-assisted Automatic Vessel Segmentation for Optical Coherence Tomography Angiography
- Author
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Xiaojun Yu, Chenkun Ge, Muhammad Zulkifal Aziz, Mingshuai Li, Perry Ping Shum, Linbo Liu, and Jianhua Mo
- Subjects
General Engineering ,Image Processing, Computer-Assisted ,General Physics and Astronomy ,Retinal Vessels ,General Materials Science ,General Chemistry ,Fluorescein Angiography ,General Biochemistry, Genetics and Molecular Biology ,Algorithms ,Tomography, Optical Coherence - Abstract
Automatic optical coherence tomography angiography (OCTA) vessel segmentation is of great significance to retinal disease diagnoses. Due to the complex vascular structure, however, various existing factors make the segmentation task challenging. This paper reports a novel end-to-end three-stage channel and position attention (CPA) module integrated graph reasoning convolutional neural network (CGNet) for retinal OCTA vessel segmentation. Specifically, in the coarse stage, both CPA and graph reasoning network (GRN) modules are integrated in between a U-shaped neural network encoder and decoder to acquire vessel confidence maps. After being directed into a fine stage, such confidence maps are concatenated with the original image and the generated fine image map as a 3-channel image to refine retinal micro-vasculatures. Finally, both the fine and refined images are fused at the refining stage as the segmentation results. Experiments with different public datasets are conducted to verify the efficacy of the proposed CGNet. Results show that by employing the end-to-end training scheme and the integrated CPA and GRN modules, CGNet achieves 94.29% and 85.62% in area under the ROC curve (AUC) for the two different datasets, outperforming the state-of-the-art existing methods with both improved operability and reduced complexity in different cases. Code is available at https://github.com/GE-123-cpu/CGnet-for-vessel-segmentation.
- Published
- 2022
41. Gliding arc discharge used for water activation: the production mechanism of aqueous NO and its role in sterilization
- Author
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Mengying Zhu, Zifeng Wang, Jinkun Chen, Linbo Liu, Wang Xi, Fugao Zhang, Li Guo, Dingxin Liu, and Mingzhe Rong
- Subjects
Acoustics and Ultrasonics ,Condensed Matter Physics ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials - Abstract
Gliding arc is a promising plasma technology for water activation due to its high energy efficiency for producing reactive nitrogen species (RNS), which is believed as the key agent for the sustained bactericidal effect of plasma-activated water (PAW). Nitric oxide (NO) is the major product of gliding arc and also widely exists in PAW, but the production mechanism of aqueous NO and its role in sterilization have been little investigated before. In this paper, NO-rich plasma effluent gas is produced by gliding arc discharge and introduced into water to produce PAW. The concentrations of gaseous and aqueous reactive species are detected, which decrease with the increasing air flowrate of the gliding arc. To clarify the contribution of plasma-induced RNS on water activation, the NO + air mixed gas is used to simulate the plasma effluent gas, and the results show that the two gases have similar gaseous composition and aqueous NO yield. Compared with the NO + Ar mixed gas with the same NO proportion, the NO + air mixed gas produces much more aqueous NO, implying that the presence of O2 significantly enhances the production of aqueous NO. The sterilization experiments demonstrate the key role of aqueous NO in sterilization, but an acidic environment is necessary for aqueous NO to achieve a potent bactericidal effect.
- Published
- 2022
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42. Microfluidic on-demand engineering of longitudinal dynamic self-assembly of particles
- Author
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Linbo Liu, Haibo Xiu, Zhonghua Ni, Haoyan Xu, and Nan Xiang
- Subjects
Microchannel ,Materials science ,Viscosity ,Microfluidics ,010401 analytical chemistry ,Mechanical engineering ,02 engineering and technology ,Microfluidic Analytical Techniques ,021001 nanoscience & nanotechnology ,01 natural sciences ,Biochemistry ,Finite element method ,Line (electrical engineering) ,0104 chemical sciences ,Analytical Chemistry ,Transverse plane ,Electrochemistry ,Environmental Chemistry ,Particle ,Self-assembly ,0210 nano-technology ,Realization (systems) ,Spectroscopy - Abstract
The lack of a simple operable method for on-demand engineering of longitudinal dynamic self-assembly of particles is one of the main problems in employing particle manipulation in biomedical research studies. Herein, a viscoelasticity-induced self-assembling microfluidic system is proposed to increase the maneuverability and orderliness of longitudinal dynamic self-assembly of particles, and achieve the on-demand control of interparticle spacings and frequencies of particles passing through an outlet. In our microfluidic system, two kinds of functional microstructures and a side-channel were designed to preprocess randomly distributed particles allowing them not to aggregate but rather to evenly distribute, and realize the on-demand control of the particle volume concentration. Randomly distributed particles could be focused into a line and become equally spaced on the center axis of a straight microchannel under transverse elastic force and longitudinal viscoelasticity-induced effective repulsive force. Besides, a finite element model was established to analyze the processes of particles flowing in each functional microstructure. Therefore, a step forward in the experimental method and realization of this microfluidic technology can provide opportunities for applications in biomedical engineering, materials science and beyond.
- Published
- 2020
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43. Droplet‐based microreactor for the production of micro/nano‐materials
- Author
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Zhonghua Ni, Nan Xiang, and Linbo Liu
- Subjects
Materials science ,Microfluidics ,010401 analytical chemistry ,Clinical Biochemistry ,Nanotechnology ,Equipment Design ,Hardware_PERFORMANCEANDRELIABILITY ,02 engineering and technology ,021001 nanoscience & nanotechnology ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Analytical Chemistry ,Micro nano ,Nano ,Hardware_INTEGRATEDCIRCUITS ,Particle Size ,Hardware_ARITHMETICANDLOGICSTRUCTURES ,Microreactor ,0210 nano-technology - Abstract
Droplet-based microreactors are of great interest to researchers due to their incredible ability in the synthesis of micro/nano-materials with multi-function and complex geometry. In recent years, a broad range of micro/nano-materials has been synthesized in droplet-based microreactors, which provide apparent advantages, such as better reproducibility, reliable automation, and accurate manipulation. In this review, we give a comprehensive and in-depth insight into droplet-based microreactors, covering fundamental research from droplet generation and manipulation to the applications of droplet-based microreactors in micro/nano-material generation. We also explore the outlook for droplet-based microreactors and challenges that lie ahead and give a possible effort direction. We hope this review will promote communications among researchers and entrepreneurs.
- Published
- 2019
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44. AN EXPERIMENTAL STUDY ON PERFORMANCE OF SHAPE MEMORY ALLOY SUSPENSION PENDULUM DAMPING SYSTEM
- Author
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Yanghong Xi, Kun Zu, Fan Tuanjie, Ergang Xiong, Linbo Liu, and Sheliang Wang
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Materials science ,lcsh:TA1-2040 ,superelasticity ,phase relation ,Pendulum ,food and beverages ,sma suspension pendulum damping system ,Shape-memory alloy ,Composite material ,Suspension (vehicle) ,equivalent damping force ,lcsh:Engineering (General). Civil engineering (General) ,Civil and Structural Engineering - Abstract
A systematic study is conducted on variation regularities for such properties of SMA wires with the diameter of wires, strain amplitude and loading cycles as the stress-strain curve, characteristic stresses, energy dissipation capacity, equivalent damping ratio. The results show: The diameter increase of SMA wires can degrade the mechanical properties of SMA wires; SMA wires can exhibit a good and stable hysteretic performance when the strain amplitude is 6% and the loading cycle is 15. Utilizing the superelasticity of SMA and combining the operating principle of the tuned mass damper, a new kind of SMA suspension pendulum damping system, which is easy to disassemble, was designed and fabricated with the trained SMA wires. Corresponding experiments were conducted to analyse the natural frequency of the damping system, phase relations between the mass vibrators and the controlled structure, variation regularity of the equivalent damping force with the mass vibrators and length of pendulum rod. The results indicate that phase relations between the mass vibrators and the controlled structure can desirably fall within 150°~180° when this damping system subjected to the sine waves and real earthquake waves. Meanwhile, the equivalent damping force increases significantly with the amplitude of external loads. In conclusion, this kind of damping system can provide a stable and efficient damping force and be simply applied to structural vibration control, thus to protect structures free from strong dynamic disasters.
- Published
- 2019
45. Estimation of Refractive Index for Biological Tissue Using Micro-Optical Coherence Tomography
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Junying Wu, Xiaojun Yu, Xianghong Wang, Linbo Liu, Yuemei Luo, Hongying Tang, Si Chen, and Xinyu Liu
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Materials science ,genetic structures ,Quantitative Biology::Tissues and Organs ,Physics::Medical Physics ,0206 medical engineering ,Biomedical Engineering ,Physics::Optics ,Image processing ,02 engineering and technology ,Cornea ,symbols.namesake ,Optics ,Optical coherence tomography ,Image Processing, Computer-Assisted ,medicine ,Animals ,medicine.diagnostic_test ,business.industry ,Cauchy distribution ,Equipment Design ,020601 biomedical engineering ,Rats ,Refractometry ,Wavelength ,Fourier transform ,symbols ,sense organs ,Tomography ,business ,Refractive index ,Tomography, Optical Coherence ,Coherence (physics) - Abstract
The refractive index of a biological tissue is required for investigating the tissue's optical properties. Efforts have been made to characterize the refractive indices of biological tissues at a single wavelength, but it is more convenient to know the Cauchy's coefficients, which provide refractive index over a wide range of wavelengths. We demonstrate a method to noninvasively provide the Cauchy's dispersion coefficients of biological tissues using a micro-optical coherence tomography. Using the short-frequency Fourier transforms, the relative optical thickness of the sample in the wavelength range of the broadband source was obtained from interferograms. The coefficients of the Cauchy's equation were estimated based on the wavelength-dependent sample thickness. We validated the proposed method using distilled water and fresh rat cornea ex vivo , and the experimental results were consistent with the reference data.
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- 2019
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46. TriD-LAMP: A pump-free microfluidic chip for duplex droplet digital loop-mediated isothermal amplification analysis
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Cui Wu, Linbo Liu, Zunzhong Ye, Jingjing Gong, Pei Hao, Jianfeng Ping, and Yibin Ying
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Microfluidics ,Escherichia coli ,Environmental Chemistry ,DNA ,Microfluidic Analytical Techniques ,Nucleic Acid Amplification Techniques ,Biochemistry ,Spectroscopy ,Fluorescent Dyes ,Analytical Chemistry - Abstract
Digital nucleic acid amplification techniques are powerful and attractive approaches for providing sensitive and absolute quantification in biology. Among these, digital loop-mediated isothermal amplification (dLAMP) shows the potential for field detection, since its robustness and independence from thermal cycling. The key of dLAMP is to generate a large number of individual droplets or microwells. However, an auxiliary precision pump is always required for sample digitalization. In addition, current systems for droplet dLAMP usually need to transfer the droplets after digitalization or amplification. Herein, we developed and evaluated a pump-free microfluidic chip for duplex droplet dLAMP (TriD-LAMP) detection. This chip was designed based on step emulsification and contains a droplet generation zone and a droplet storage zone. Droplets are formed through the step due to the difference in Laplace pressure. There are 64 parallel nozzles that could generate tens of thousands of uniform droplets manually (variation5%). The storage zone for droplets collection was previously filled with oil containing fluorosurfactant that keeps the droplets from fusing and evaporation during the amplification. Therefore, this custom chip is able to perform all stages of the dLAMP process without transferring droplets. Combined with the optimized fluorescent probe method, the chip achieves accurate quantification of the E. coli DNA down to 19.8 copies/μL. As a proof of concept, the simultaneous quantification of two targets was successfully realized on this custom chip. Conclusively, this integrated, pump-free TriD-LAMP chip can provide a promising tool for multiple targets detection in clinical diagnostics and point-of-care applications.
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- 2022
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47. Designing Self-floating Anisotropic Macroporous Hydrogel by Step Emulsification and Buoyancy-assisted Microfluidics
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Xing Huang, Linbo Liu, Jie-Li Wang, Mingcheng Bi, Cong Liu, Wenya Liao, Pengfei Wang, Junfeng Liu, Zhanglin Hou, Zhongbin Xu, and Fangfu Ye
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General Chemical Engineering ,Environmental Chemistry ,General Chemistry ,Industrial and Manufacturing Engineering - Published
- 2022
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48. Influence of the pandemic dissemination of COVID-19 on facial rejuvenation: A survey of Twitter
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Ran Pang, Xu Cheng, Guangshuai Li, Han Zhang, Zhiru Wei, Linbo Liu, Wenhui Liu, and Zong Chen
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Facial rejuvenation ,Pneumonia, Viral ,Twitter ,Face (sociological concept) ,Dermatology ,Cosmetic Techniques ,Public opinion ,Public interest ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Betacoronavirus ,0302 clinical medicine ,facial rejuvenation ,Humans ,Rejuvenation ,Social media ,Pandemics ,Covid‐19 ,business.industry ,SARS-CoV-2 ,Sentiment analysis ,COVID-19 ,Advertising ,word cloud ,Original Contribution ,030220 oncology & carcinogenesis ,Face ,Public Opinion ,sentiment analysis ,Tag cloud ,Psychology ,business ,Coronavirus Infections ,Social Media - Abstract
Background With the pandemic dissemination of COVID‐19, attitude and sentiment surrounding facial rejuvenation have evolved rapidly. Aims The purpose of this study was to understanding the impact of pandemic on the attitude of people towards facial skin rejuvenation. Methods Twitter data related to facial rejuvenation were collected from January 1, 2020, to April 30, 2020. Sentiment analysis, frequency analysis, and word cloud were performed to analyze the data. Statistical analysis included two‐tailed t‐tests and chi‐square tests. Results In the post‐declaration, the number of tweets about facial rejuvenation increased significantly, and the search volume in Google Trends decreased. Negative public emotions increased, but positive emotions still dominate. The words frequency of “discounts” and “purchase” decreased. The dominant words in word cloud were “Botox”, “facelift”, “hyaluronic” and “skin”. Conclusion The public has a positive attitude toward facial rejuvenation during the pandemic. In particular, minimally invasive procedures dominate the mainstream, such as “Botox”, “Hyaluronic acid” and “PRP”. The practitioners could understand the change of the public interest in facial rejuvenation in time and decide what to focus on.
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- 2020
49. Evaluating Micro-Optical Coherence Tomography as a Feasible Imaging Tool for Pancreatic Disease Diagnosis
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Qianshan Ding, Honggang Yu, Yunchao Deng, Xiaojun Yu, Yuemei Luo, Linbo Liu, Ganggang Mu, Zhaohui Yuan, Chi Hu, and School of Electrical and Electronic Engineering
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Pancreatic Imaging ,Pancreatic disease ,genetic structures ,medicine.diagnostic_test ,business.industry ,Histology ,medicine.disease ,eye diseases ,Atomic and Molecular Physics, and Optics ,Serous fluid ,Imaging Tool ,Optical coherence tomography ,Pancreatic cancer ,Electrical and electronic engineering [Engineering] ,Medical imaging ,Medicine ,sense organs ,Tomography ,Optical Coherence Tomography ,Electrical and Electronic Engineering ,business ,Nuclear medicine - Abstract
Pancreatic cancer is one of the leading causes of cancer mortality worldwide due to the lack of reliable tools for early diagnosis of this cancer. In this study, we evaluated the feasibility of micro-optical coherence tomography (μOCT) as an imaging tool for the diagnosis of pancreatic cancers. Specifically, we constructed a μOCT device that achieves a resolution of 1.67 ± 0.01 μm and 1.79 ± 0.01 μm in axial and lateral directions, respectively, and acquired three-dimensional μOCT images of mouse, rat, and human pancreatic specimens ex vivo. We compared the results of μOCT with those of the corresponding histology. In μOCT images of normal pancreatic specimens, the detailed cellular and subcellular-level pancreatic microstructures, e.g., the islet of Langerhans (IL), IL cell nuclei, blood vessels, and serous acini, could be clearly resolved in different cases. To the best of our knowledge, this study is the first to demonstrate that the cellular and subcellular structures of pancreatic tissues were identified using OCT. More importantly, we showed that these normal cellular-level structures were lost in μOCT images of cancerous specimens, demonstrating the feasibility of differentiating malignant lesions from normal tissues using μOCT. Moving forward, the development of an intraoperative imaging device may realize optical biopsies in vivo or real-time cellular-resolution examination of specimens from needle aspiration biopsies. Ministry of Education (MOE) Nanyang Technological University National Medical Research Council (NMRC) National Research Foundation (NRF) Accepted version This work was supported in part by the National Natural Science Foundation of China under Grant 61705184, the Fundamental Research Funds for the Central Universities (G2018KY0308), in part by the National Research Foundation of Singapore (NRF-CRP13-2014-05), in part by the Ministry of Education of Singapore (MOE2013-T2-2-107), in part by the National Medical Research Council of Singapore (NMRC/CBRG/0036/2013), and in part by the NTU-AIT-MUV Program in Advanced Biomedical Imaging (NAM/15005).
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- 2019
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50. Combination therapy with cystic fibrosis transmembrane conductance regulator modulators augment the airway functional microanatomy
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Marina Mazur, William E. Grizzle, George M. Solomon, Guillermo J. Tearney, Susan E. Birket, Peter A. Sloane, Vivian Y. Lin, Linbo Liu, Grace H. Houser, Justin Hanes, Courtney M. Fernandez, Kengyeh K. Chu, Steven M. Rowe, Suresh Shastry, and Eric J. Sorscher
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Cystic Fibrosis ,Physiology ,Mucociliary clearance ,Drug Evaluation, Preclinical ,Mutation, Missense ,Cystic Fibrosis Transmembrane Conductance Regulator ,Quinolones ,Pharmacology ,Aminophenols ,Cystic fibrosis ,Membrane Potentials ,Amiloride ,Ivacaftor ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,medicine ,Animals ,Humans ,Chloride Channel Agonists ,Cells, Cultured ,Ion transporter ,biology ,Colforsin ,Cell Biology ,medicine.disease ,Mucus ,Cystic fibrosis transmembrane conductance regulator ,030104 developmental biology ,030228 respiratory system ,Mechanism of action ,NIH 3T3 Cells ,Call for Papers ,biology.protein ,Drug Therapy, Combination ,medicine.symptom ,medicine.drug - Abstract
Recently approved therapies that modulate CFTR function have shown significant clinical benefit, but recent investigations regarding their molecular mechanism when used in combination have not been consistent with clinical results. We employed micro-optical coherence tomography as a novel means to assess the mechanism of action of CFTR modulators, focusing on the effects on mucociliary clearance. Primary human airway monolayers from patients with a G551D mutation responded to ivacaftor treatment with increased ion transport, airway surface liquid depth, ciliary beat frequency, and mucociliary transport rate, in addition to decreased effective viscosity of the mucus layer, a unique mechanism established by our findings. These endpoints are consistent with the benefit observed in G551D patients treated with ivacaftor, and identify a novel mechanism involving mucus viscosity. In monolayers derived from F508del patients, the situation is more complicated, compounded by disparate effects on CFTR expression and function. However, by combining ion transport measurements with functional imaging, we establish a crucial link between in vitro data and clinical benefit, a finding not explained by ion transport studies alone. We establish that F508del cells exhibit increased mucociliary transport and decreased mucus effective viscosity, but only when ivacaftor is added to the regimen. We further show that improvement in the functional microanatomy in vitro corresponds with lung function benefit observed in the clinical trials, whereas ion transport in vitro corresponds to changes in sweat chloride. Functional imaging reveals insights into clinical efficacy and CFTR biology that significantly impact our understanding of novel therapies.
- Published
- 2016
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