分类： 核科学技术 >> 核科学与技术 提交时间： 2025-03-28
Xiangpeng Meng
Yuanyuan Liu
Bin Wu
Yu Wang
Jing Wang
Lai Zhou
Ao Ju
Yunshi Xiao
Qinjian Cao
Zhi Zeng
Qian Yue
Jianping Cheng
摘要： Efficiency calibration is a critical step that enables the conversion of the detectors’ count rate into the activityof radionuclides in the examined parts for in vivo measurement. However, to date, there hasn’t been awell-accepted framework for efficiency calibration. As such, it is often found researchers employ various kindsof anthropomorphic phantoms with considerably different patterns of radionuclide distribution coupling withdrastically different numbers of detectors to derive the calibration factor, rendering the cross-comparison amongstudies challenging. Moreover, some studies employ virtual calibration, whereas others prefer experimental calibration,though their equivalency has not been fully explored. In this paper, focusing on in vivo measurement ofPb-210 in the skull, a promising technique for individualized reconstruction of radon exposure is presented, anda detailed framework for efficiency calibration covering key issues mentioned above is provided. To be specific,physical phantoms of Pb-210 in the skull are developed based on the anatomical characteristics of a Chineseadult reference male, along with the corresponding computational phantoms constructed from computed tomographyscan. In comparison, the average deviations between simulation and experimental results are within 4%for efficiency calibration at the top, left, and right sides of the head across varying detection distances. Furthermore,based on the investigation of Pb-210 distribution regions reported in literature, the calculation methodfor Pb-210 activity is improved to account for different source distributions and joint measurements with multipledetectors. The results are useful for determining the appropriate conversion procedure under differentmeasurement conditions.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
Yan, Xinqiang
Yan, Xinqiang
Yan, Xinqiang
Xie, Zhentian
Zhang, Xiaoliang
Pedersen, Jan Ole
Zhang, Xiaoliang
摘要： Radiative antenna techniques, e.g., dipole and monopole, have been proposed for radiofrequency (RF) coil array designs in ultrahigh field MRI to obtain stronger B-1 field and higher signal-to-noise ratio (SNR) gain in the areas deep inside human head or body. It is known that element decoupling performance is crucial to SNR and parallel imaging ability of array coil and has been a challenging issue in radiative antenna array designs for MR imaging. Magnetic wall or induced current elimination (ICE) technique has proven to be a simple and effective way of achieving sufficient decoupling for radiative array coils experimentally. In this study, this decoupling technique for radiative coil array was analyzed theoretically and verified by a simulation study. The decoupling conditions were derived and obtained from the theory. By applying the predicated decoupling conditions, the isolation of two radiative elements could be improved from about -8 dB to better than -35 dB. The decoupling performance has also been validated by current distribution along the radiative elements and magnetic field profiles in a water phantom. (c) 2015 Wiley Periodicals, Inc.
分类： 物理学 >> 普通物理:统计和量子力学,量子信息等 提交时间： 2017-11-17
Hui Xie
Lili Zeng
Shaogao Zeng
Xin Lu
Xin Zhao
Guicheng ZhangZhengchao Tu
Hongjiang Xu
Ling Yang
Xiquan Zhang
Wenhui Hua
摘要： The structural superposition of DPP-IV complex with Alogliptin and Linagliptin displayed a similar binding mode. The butynyl of Linagliptin and cyanobenzyl of Alogliptin occupy the S1 pocket which therefore could be mutually switched. Thus a pharmacophore hybridization of Alogliptin was initiated and led to a novel DPP-IV inhibitor 61. Though it did not exhibit desired activity (IC50= 0.2 礛), the butynyl compound acts as a lead compound triggered a following structural optimization. A novel series of potent DPP-IV inhibitors represented by compound 77 (IC50= 0.36 nM) were obtained with a robust pharmacokinetic profile and better in vitro and in vivo efficacy than Alogliptin.
分类： 生物学 >> 生态学 提交时间： 2017-11-17
摘要： Drug compliance is critical for the patients with chronic diseases like diabetes. In our continuous effort to find better glucose lowering agents, an exploration for long-acting DPP-4 inhibitor had been launched. Based on our previous reported compound 111 bearing a pyrrolopyrimidine scaffold, lead compound 114 (IC50 = 2.3 nM, t1/2(rat) = 5.46 h) was rapidly determined with the pharmacokinetic superiority. Further SAR study indicated that the pyrrole ring was generally tolerable for variation, in which the β-substitution gave a better DPP-4 affinity. In depth evaluation on β position of pyrrole ring brought up with highly potent compound 124 (IC50 = 0.76 nM, t1/2(rat) = 7.89 h). In vivo pharmacodynamics tests demonstrated a similar or even slightly better sustained DPP-4 inhibition of compound 114 and 124 compared with the first marketed once-weekly drug Trelagliptin in this category, indicating that improvement of DPP-4 inhibitory activity or pharmacokinetic profile might be both feasible ways to rapid generation of long-acting DPP-4 inhibitors.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
Sun, Xianlei
Gao, Duo
Gao, Liquan
Zhang, Chenran
Yu, Xinhe
Jia, Bing
Wang, Fan
Liu, Zhaofei
Sun, Xianlei
Gao, Duo
Gao, Liquan
Zhang, Chenran
Yu, Xinhe
Jia, Bing
Wang, Fan
Liu, Zhaofei
Wang, Fan
摘要： Significant evidence has indicated that tumor-associated macrophages (TAMs) play a critical role in the proliferation, invasion, angiogenesis, and metastasis of a variety of human carcinomas. In this study, we investigated whether near-infrared fluorescence (NIRF) imaging using a macrophage mannose receptor (MMR; CD206)-targeting agent could be used to noninvasively visualize and quantify changes in TAMs in vivo. The CD206-targeting NIRF agent, Dye-anti-CD206, was prepared and characterized in vitro and in vivo. By using NIRF imaging, we were able to noninvasively image tumor-infiltrating macrophages in the 4T1 mouse breast cancer model. Importantly, longitudinal NIRF imaging revealed the depletion of macrophages in response to zoledronic acid (ZA) treatment. However, ZA alone did not lead to the inhibition of 4T1 tumor growth. We therefore combined anti-macrophage ZA therapy and tumor cytotoxic docetaxel (DTX) therapy in the mouse model. The results demonstrated that this combination strategy could significantly inhibit tumor growth as well as tumor metastasis to the lungs. Based on these findings, we concluded that CD206-targeted molecular imaging can sensitively detect the dynamic changes in tumor-infiltrating macrophages, and that the combination of macrophage depletion and cytotoxic therapy is a promising strategy for the effective treatment of solid tumors.
分类： 物理学 >> 普通物理:统计和量子力学,量子信息等 提交时间： 2017-05-02
Tian, Y [Tian, Ying][ 1 ]
Sun, J [Sun, Jing][ 1 ]
Yan, HJ [Yan, Huaijiang][ 2 ]
Teng, ZG [Teng, Zhaogang][ 1 ]
Zeng, LY [Zeng, Leyong][ 3 ]
Liu, Y [Liu, Ying][ 1 ]
Li, YJ [Li, Yanjun][ 1 ]
Wang, JD [Wang, Jiandong][ 4 ]
Wang, SJ [Wang, Shouju][ 1 ]
Lu, GM [Lu, Guangming][ 1 ]
摘要： Detection of malignant cells from malignant effusion is crucial to establish or adjust therapies of patients with cancer. The conventional qualitative detection in malignant pleuroperitoneal effusion is cytological analysis, which is time-consuming and complicated. Therefore, a faster and more convenient detection strategy is urgently needed. In this study, we report a rapid method to detect malignant cells from malignant pleuroperitoneal effusion (hydrothorax and ascites) of patients using IR-808, a tumor-targeted near-infrared (NIR) fluorescent heptamethine dye (tNRI dye), which exhibited superior labeling efficacy without specific conjugation to biomarkers. The targeted imaging performance toward malignant cells using IR-808 was confirmed by comparing with normal cells, and the fluorescence stability assay of IR- 808 in malignant effusion was performed from 1 h to 48 h. In order to save time and dose, the incubation time and concentration were optimized to 10 min and 5 mM, which were used to detect malignant cells from 28 clinical samples of malignant pleuroperitoneal effusion. The results revealed that IR-808 could be internalized selectively by malignant cells of samples, and these malignant cells could be easily distinguished from normal cells under a fluorescence microscope. The positive rates between cytological analysis and the IR-808 staining method were 86% (24/28) and 79% (22/28), respectively. An excellent concordance level (Kappa 1⁄4 0.752, P < 0.001) was observed between the two methods. Our results indicated that IR-808, a new NIR fluorescent heptamethine dye with unique optical imaging and tumor targeting properties, could provide a fast and simple way to detect a broad spectrum of malignant cells from malignant pleuroperitoneal effusion in patients.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
Yan, Xinqiang
Xue, Rong
Yan, Xinqiang
Wei, Long
Yan, Xinqiang
Wei, Long
Zhang, Xiaoliang
Zhang, Xiaoliang
Xue, Rong
摘要： Radio-frequency coil arrays using dipole antenna technique have been recently applied for ultrahigh field magnetic resonance (MR) imaging to obtain the better signal-noise-ratio (SNR) gain at the deep area of human tissues. However, the unique structure of dipole antennas makes it challenging to achieve sufficient electromagnetic decoupling among the dipole antenna elements. Currently, there is no decoupling methods proposed for dipole antenna arrays in MR imaging. The recently developed magnetic wall (MW) or induced current elimination decoupling technique has demonstrated its feasibility and robustness in designing microstrip transmission line arrays, L/C loop arrays and monopole arrays. In this study, we aim to investigate the possibility and performance of MW decoupling technique in dipole arrays for MR imaging at the ultrahigh field of 7T. To achieve this goal, a two-channel MW decoupled dipole array was designed, constructed and analyzed experimentally through bench test and MR imaging. Electromagnetic isolation between the two dipole elements was improved from about -3.6 dB (without any decoupling treatments) to -16.5 dB by using the MW decoupling method. MR images acquired from a water phantom using the MW decoupled dipole array and the geometry factor maps were measured, calculated and compared with those acquired using the dipole array without decoupling treatments. The MW decoupled dipole array demonstrated well-defined image profiles from each element and had better geometry factor over the array without decoupling treatments. The experimental results indicate that the MW decoupling technique might be a promising solution to reducing the electromagnetic coupling of dipole arrays in ultrahigh field MRI, consequently improving their performance in SNR and parallel imaging.
分类： 生物学 >> 生物物理学 >> 影像医学与生物医学工程 提交时间： 2016-05-11
Gao, Duo
Gao, Liquan
Zhang, Chenran
Liu, Hao
Jia, Bing
Wang, Fan
Liu, Zhaofei
Gao, Duo
Gao, Liquan
Zhang, Chenran
Liu, Hao
Jia, Bing
Wang, Fan
Liu, Zhaofei
Zhu, Zhaohui
Wang, Fan
摘要： Integrin alpha v beta 6 is widely upregulated in variant malignant cancers but is undetectable in normal organs, making it a promising target for cancer diagnostic imaging and therapy. Using streptavidin-biotin chemistry, we synthesized an integrin alpha v beta 6-targeted near-infrared phthalocyanine dye-labeled agent, termed Dye-SA-B-HK, and investigated whether it could be used for cancer imaging, optical imaging-guided surgery, and phototherapy in pancreatic cancer mouse models. Dye-SA-B-HK specifically bound to integrin alpha v beta 6 in vitro and in vivo with high receptor binding affinity. Using small-animal optical imaging, we detected subcutaneous and orthotopic BxPC-3 human pancreatic cancer xenografts in vivo. Upon optical image-guidance, the orthotopically growing pancreatic cancer lesions could be successfully removed by surgery. Using light irradiation, Dye-SA-B-HK manifested remarkable antitumor effects both in vitro and in vivo. F-18-FDG positron emission tomography (PET) imaging and ex vivo fluorescence staining validated the observed decrease in proliferation of treated tumors by Dye-DA-B-HK phototherapy. Tissue microarray results revealed overexpression of integrin alpha v beta 6 in over 95% cases of human pancreatic cancer, indicating that theranostic application of Dye-DA-B-HK has clear translational potential. Overall, the results of this study demonstrated that integrin alpha v beta 6-specific Dye-SA-B-HK is a promising theranostic agent for the management of pancreatic cancer. (C) 2015 Elsevier Ltd. All rights reserved.
提交时间： 2017-05-02
Ren, WZ [Ren, Wenzhi][ 1,2 ]
Yan, Y [Yan, Yong][ 3,4 ]
Zeng, LY [Zeng, Leyong][ 1,2 ]
Shi, ZZ [Shi, Zhenzhi][ 1,2 ]
Gong, A [Gong, An][ 1,2 ]
Schaaf, P [Schaaf, Peter][ 3,4 ]
Wang, D [Wang, Dong][ 3,4 ]
Zhao, JS [Zhao, Jinshun][ 5 ]
Zou, BB [Zou, Baobo][ 5 ]
Yu, HS [Yu, Hongsheng][ 6 ]
Chen, G [Chen, Ge][ 7 ]
Brown, EMB [Brown, Eric Michael Bratsolias][ 8 ]
Wu, AG [Wu, Aiguo][ 1,2 ]
摘要： White TiO2 nanoparticles [NPs] have been widely used for cancer photodynamic therapy based on their ultraviolet light-triggered properties. To date, biomedical applications using white TiO2 NPs have been limited, since ultraviolet light is a well-known mu
分类： 生物学 >> 生物物理学 >> 生物力学与生物流变学 提交时间： 2016-05-12
Zhao, Ye
Wang, Jun
Chen, Shaopeng
Yuan, Hang
Xu, An
Wu, Lijun
Ma, Xiaoyan
Hang, Haiying
Ma, Xiaoyan
Hang, Haiying
Wang, Jun
Chen, Shaopeng
Yuan, Hang
Xu, An
Wu, Lijun
Wu, Lijun
摘要： Previously reported studies have demonstrated the involvement of p21(Waf1/CIP1) in radiation-induced bystander effects (RIBE). Mouse embryonic fibroblasts (MEFs) lacking Hus1 fail to proliferate in vitro, but inactivation of p21 allows for the continued growth of Hus1-deficient cells, indicating the close connection between p21 and Hus1 cells. In this study, wildtype MEFs, Hus1(+/+)p21(-/-) MEFs and p21(-/-)Hus1(-/-) MEFs were used in a series of radiation-induced bystander effect experiments, the roles of p21 and Hus1 in the induction and transmission of radiation-induced damage signals were investigated. Our results showed that after 5 cGy alpha particle irradiation, wild-type MEFs induced significant increases in gamma-H2AX foci and micronuclei formation in bystander cells, whereas the bystander effects were not detectable in p21(-/-)Hus1(+/+) MEFs and were restored again in p21(-/-)Hus1(-/-) MEFs. Media transfer experiments showed that p21(-/-)Hus1(+/+) MEFs were deficient in the production bystander signals, but could respond to bystander signals. We further investigated the mitogen-activated protein kinases (MAPKs) that might be involved in the bystander effects. It was found that although knocking out p21 did not affect the expression of connexin43 and its phosphorylation, it did result in inactivation of some MAPK signal pathway kinases, including JNK1/2, ERK1/2 and p38, as well as a decrease in reactive oxygen species (ROS) levels in irradiated cells. However, the activation of MAPK kinases and the ROS levels in irradiated cells were restored in the cell line by knocking out Hus1. These results suggest that p21(Waf1/CIP1) and Hus1 play crucial roles in the generation and transmission of bystander damage signals after low-dose a particle irradiation. (C) 2015 by Radiation Research
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
Liu, Renfa
Dai, Zhifei
Shi, Jiyun
Fan, Di
Wang, Fan
Shi, Jiyun
Wang, Fan
Li, Yaqian
Tian, Jie
Jing, Lijia
摘要： This Article reported the fabrication of a robust theranostic cerasome encapsulating indocyanine green (ICG) by incorporating 1,2-distearoyl-sn-glycero-3-phosphoethanol-amine-N-[carboxy(polyethylene glycol)2000]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid monoamide (DSPE-PEG(2000)-DOTA), followed by chelating radioisotope of Lu-177. Its applications in optical and nuclear imaging of tumor uptake and biodistribution, as well as photothermal killing of cancer cells, were investigated. It was found that the obtained cerasome could act efficiently as fluorescence contrast agent as well as nuclear imaging tracer. Encapsulating ICG into cerasome could protect ICG from degradation, aggregation, and fast elimination from body, resulting in remarkable improvement in near-infrared fluorescence imaging, photothermal stability, and in vivo pharmacokinetic profile. Both fluorescence and nuclear imaging showed that such agent could selectively accumulate in tumor site after intravenous injection of the cerasome agent into Lewis lung carcinoma tumor bearing mice, resulting in efficient photothermal ablation of tumor through a one-time NIR laser irradiation at the best time window. The ability to track the uptake of cerasomes on a whole body basis could provide researchers with an excellent tool for developing cerasome-based drug delivery agents, especially the strategy of labeling cerasomes with theranostic radionuclide Lu-177, enabling the ability of the Lu-177-labeled cerasomes for radionuclide cancer therapy and even the combined therapy.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
摘要： The prokaryotic mechanosensitive channel of large conductance (MscL) is a pressure-relief valve protecting the cell from lysing during acute osmotic downshock. When the membrane is stretched, MscL responds to the increase of membrane tension and opens a nonselective pore to about 30 angstrom wide, exhibiting a large unitary conductance of similar to 3 nS. A fundamental step toward understanding the gating mechanism of MscL is to decipher the molecular details of the conformational changes accompanying channel opening. By applying fusion-protein strategy and controlling detergent composition, we have solved the structures of an archaeal MscL homolog from Methanosarcina acetivorans trapped in the closed and expanded intermediate states. The comparative analysis of these two new structures reveals significant conformational rearrangements in the different domains of MscL. The large changes observed in the tilt angles of the two transmembrane helices (TM1 and TM2) fit well with the helix-pivoting model derived from the earlier geometric analyses based on the previous structures. Meanwhile, the periplasmic loop region transforms from a folded structure, containing an.-shaped loop and a short beta-hairpin, to an extended and partly disordered conformation during channel expansion. Moreover, a significant rotating and sliding of the N-terminal helix (N-helix) is coupled to the tilting movements of TM1 and TM2. The dynamic relationships between the N-helix and TM1/TM2 suggest that the N-helix serves as a membrane-anchored stopper that limits the tilts of TM1 and TM2 in the gating process. These results provide direct mechanistic insights into the highly coordinated movement of the different domains of the MscL channel when it expands.
分类： 生物学 >> 生物物理学 >> 细胞生物学 提交时间： 2016-05-05
Ding, Jingzhen
Chen, Shuliang
Ferro-Novick, Susan
Segarra, Veronica A.
Lemmon, Sandra K.
Cai, Huaqing
摘要： Coat protein complexes contain an inner shell that sorts cargo and an outer shell that helps deform the membrane to give the vesicle its shape. There are three major types of coated vesicles in the cell: COPII, COPI, and clathrin. The COPII coat complex facilitates vesicle budding from the endoplasmic reticulum (ER), while the COPI coat complex performs an analogous function in the Golgi. Clathrin-coated vesicles mediate traffic from the cell surface and between the trans-Golgi and endosome. While the assembly and structure of these coat complexes has been extensively studied, the disassembly of COPII and COPI coats from membranes is less well understood. We describe a proteomic and genetic approach that connects the J-domain chaperone auxilin, which uncoats clathrin-coated vesicles, to COPII and COPI coat complexes. Consistent with a functional role for auxilin in the early secretory pathway, auxilin binds to COPII and COPI coat subunits. Furthermore, ER-Golgi and intra-Golgi traffic is delayed at 15 degrees C in swa2 Delta mutant cells, which lack auxilin. In the case of COPII vesicles, we link this delay to a defect in vesicle fusion. We propose that auxilin acts as a chaperone and/or uncoating factor for transport vesicles that act in the early secretory pathway.
分类： 物理学 >> 普通物理:统计和量子力学,量子信息等 提交时间： 2017-05-02
He, Y [He, Yu][ 1 ]
Hu, ZW [Hu, Zhiwei][ 2 ]
Ren, MD [Ren, Mengda][ 1 ]
Ding, CK [Ding, Changkun][ 3 ]
Chen, P [Chen, Peng][ 4 ]
Gu, Q [Gu, Qun][ 4 ]
Wu, Q [Wu, Qiong][ 1,5,6 ]
摘要： Two types of fibers were prepared by using bio- based materials: a mono-filament made from poly(3- hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and a multi-filament made from poly(3-hydroxybutyrate-co-3- hydroxyvalerate) (PHBV) and polylactic acid (PLA) blend. The two fibers were evaluated for mechanical properties, biocompatibility and degradability for the potential appli- cation as medical sutures. The PHBHHx fiber showed remarkable biocompatibility by H.E. Stainning, with very little impact to the surrounding tissues. The degradation of the fiber was observed by SEM after implantation for 36 weeks, and the major degradation product was detected after 96 weeks. Consistently, the PHBHHx fiber main- tained more than half of the mechanical properties after 96 weeks. The other fiber was prepared by twisting PHBV/PLA blend strands to a bunch, and showed high biocom- patibility and relatively high degradability. The bunched structure loosed after 36 weeks of implantation. These low- cost and easily prepared fibers have great potential in medical applications, since they could avoid the formation of fibrous capsule, reduce the size of scar, and degrade into non-toxic and even beneficial products.
提交时间： 2017-04-06
摘要： In this study, chlorobenzene (CB) vapor assistant annealing (VAA) method is employed to make high quality perovskite films and produce high efficiency CH3NH3PbI3-xClx perovskite solar cells. The perovskite films made by this method present several advanta
分类： 物理学 >> 普通物理:统计和量子力学,量子信息等 提交时间： 2017-04-06
摘要： Two types of fibers were prepared by using bio-based materials: a mono-filament made from poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and a multi-filament made from poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and polylactic acid (PLA) b
分类： 生物学 >> 生物物理学 >> 生物力学与生物流变学 提交时间： 2016-05-15
Wan, Zhengpeng
Chen, Xiangjun
Chen, Yingjia
Wang, Jing
Cao, Yiyun
Liu, Wanli
Chen, Haodong
Wang, Fei
Tang, Zhuo
Ji, Qinghua
Lou, Jizhong
摘要： B lymphocytes use B cell receptors (BCRs) to sense the physical features of the antigens. However, the sensitivity and threshold for the activation of BCRs resulting from the stimulation by mechanical forces are unknown. Here, we addressed this question using a double-stranded DNA-based tension gauge tether system serving as a predefined mechanical force gauge ranging from 12 to 56 pN. We observed that IgM-BCR activation is dependent on mechanical forces and exhibits a multi-threshold effect. In contrast, the activation of isotype-switched IgG- or IgE-BCR only requires a low threshold of less than 12 pN, providing an explanation for their rapid activation in response to antigen stimulation. Mechanistically, we found that the cytoplasmic tail of the IgG-BCR heavy chain is both required and sufficient to account for the low mechanical force threshold. These results defined the mechanical force sensitivity and threshold that are required to activate different isotyped BCRs.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-05
Li, Dan
Chen, Yuanyuan
Wang, Xia
Chen, Xin
Liu, Boli
Jia, Hongmei
Deuther-Conrad, Winnie
Steinbach, Joerg
Brust, Peter
Jia, Bing
Dong, Chengyan
摘要： We have designed and synthesized a series of cyclopentadienyl tricarbonyl rhenium complexes containing a 5,6-dimethoxyisoindoline or a 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline pharmacophore as sigma(2) receptor ligands. Rhenium compound 20a possessed low nanomolar sigma(2) receptor affinity (K-i = 2.97 nM) and moderate subtype selectivity (10-fold). Moreover, it showed high selectivity toward vesicular acetylcholine transporter (2374-fold), dopamine D-2L receptor, NMDA receptor, opiate receptor, dopamine transporter, norepinephrine transporter, and serotonin transporter. Its corresponding radiotracer [Tc-99m]20b showed high uptake in a time- and dose-dependent manner in DU145 prostate cells and C6 glioma cells. In addition, this tracer exhibited high tumor uptake (5.92% ID/g at 240 min) and high tumor/blood and tumor/muscle ratios (21 and 16 at 240 min, respectively) as well as specific binding to sigma receptors in nude mice bearing C6 glioma xenografts. Small animal SPECT/CT imaging of [Tc-99m]20b in the C6 glioma xenograft model demonstrated a clear visualization of the tumor at 180 min after injection.
分类： 生物学 >> 生物物理学 >> 免疫学 提交时间： 2016-05-05
Zhu, Danming
Liu, Longchao
Yang, Dan
Bian, Yingjie
Sun, Zhichen
He, Junming
Zhang, Liguo
Peng, Hua
Fu, Yang-Xin
Liu, Longchao
Bian, Yingjie
Sun, Zhichen
Fu, Sherry
Fu, Yang-Xin
Su, Lishan
摘要： Development of therapeutic vaccines/strategies to control chronic hepatitis B virus (HBV) infection has been challenging because of HBV-induced tolerance. In this study, we explored strategies for breaking tolerance and restoring the immune response to the HBV surface Ag in tolerant mice. We demonstrated that immune tolerance status is attributed to the level and duration of circulating HBsAg in HBV carrier models. Removal of circulating HBsAg by a monoclonal anti-HBsAg Ab in tolerant mice could gradually reduce tolerance and reestablish B cell and CD4(+) T cell responses to subsequent Engerix-B vaccination, producing protective IgG. Furthermore, HBsAg-specific CD8(+) T cells induced by the addition of a TLR agonist resulted in clearance of HBV in both serum and liver. Thus, generation of protective immunity can be achieved by clearing extracellular viral Ag with neutralizing Abs followed by vaccination.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-11
摘要： Long noncoding RNAs (IncRNAs), which have emerged in recent years as a new and crucial layer of gene regulators, regulate various biological processes such as carcinogenesis and metastasis. HOTAIR (Hox transcript antisense intergenic RNA), a lncRNA overexpressed in most human cancers, has been shown to be an oncogenic lncRNA. Here, we explored the role of HOTAIR in HeLa cells and searched for proteins regulated by HOTAIR. To understand the mechanism of action of HOTAIR from a systems perspective, we employed a quantitative proteomic strategy to systematically identify potential targets of HOTAIR. The expression of 170 proteins was significantly dys-regulated after inhibition of HOTAIR, implying that they could be potential targets of HOTAIR. Analysis of this data at the systems level revealed major changes in proteins involved in diverse cellular components, including the cytoskeleton and the respiratory chain. Further functional studies on vimentin (VIM), a key protein involved in the cytoskeleton, revealed that HOTAIR exerts its effects on migration and invasion of HeLa cells, at least in part, through the regulation of VIM expression. Inhibition of HOTAIR leads to mitochondrial dysfunction and ultrastructural alterations, suggesting a novel role of HOTAIR in maintaining mitochondrial function in cancer cells. Our results provide novel insights into the mechanisms underlying the function of HOTAIR in cancer cells. We expect that the methods used in this study will become an integral part of functional studies of IncRNAs.
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