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1. chinaXiv:201708.00176 [pdf]

佛山市生物医药产业专利分析与发展策略若干建议.doc

庞弘燊
Subjects: Biology >> Biomedical Laboratory Science

由于生物医药产业具有巨大的经济效益、社会效益,生物医药产业已经成为许多国家的朝阳产业。对于佛山市的产业发展来说,因为生物医药有着广阔的发展前景,将是佛山市今后的大力发展方向。本论文通过对佛山市的生物医药相关技术领域内的专利进行检索分析,从专利文献研究的角度分析技术领域内研究现状,梳理技术布局,了解相关技术研发的主要应用方向以及优劣势,对比佛山市自身的技术特点,制定专利布局实施方案建议。包括提高专利保护、管理、运用意识;优化产业结构及布局,把握各产业不同发展方式;提升现有技术竞争能力;建立风险预警机制,推送专利信息服务;优化发展环境等方面的具体建议。

submitted time 2017-08-08 Hits3058Downloads582 Comment 0

2. chinaXiv:201707.00063 [pdf]

Mouse model with age-dependent immune response and immune-tolerance for HBV infection

Xuerui,Yi
Subjects: Biology >> Biomedical Laboratory Science

Objective: Viral clearance of human HBV infection largely depends on the age of exposure, so a mouse model with age-dependent immune response and immune-tolerance for HBV infection is essential. Methods: HBVRag1 mice were generated by crossing Rag1-/- mice with HBV-Tg mice. The differences between adult and young HBVRag1 mice were detected after adoptive transfer of splenocytes. Immune tolerance was evaluated by quantitative hepatitis B core antibody (qAnti-HBc) assay, adoptive transfer, and modulation of gut microbiota with antibiotic. Results: After HBVRag1 mouse reconstitution, adult mice showed obvious HBV-dependent inflammation and hepatocytes damage, cleared HBsAg and generated HBsAb and HBcAb, but young mice never developed ALT elevation, and only generated HBcAb with persistence of HBsAg. In addition, for adult mice, more hepatic CD8+T and B cells promoted clearance of HBsAg 30 days after lymphocytes transfer, and for young mice, higher levels of cytokines link to the persistence of viral antigens during initiation of immune response towards HBV. The level of qAnti-HBc increased significantly with the time of adoptive transfer in young mice, but decreased significantly in adult within our model. This mimics kinetic changes of human HBV infection regarding qAnti-HBc level. Also, the age-related tolerance in this model was different from which was in HBV-Tg mice, and can be regulated through modulation of gut microbiota. Meanwhile, GS-9620 can achieve inhibition of HBsAg, but HBV vaccine just clears limited HBsAg within the model. Conclusions: Here, we described a mouse model with age-dependent immune response and immune tolerance of HBV infection which could mimic chronic HBV infection in human. It will open a door for evaluating new therapeutic approaches before clinical trials.

submitted time 2017-07-11 Hits3841Downloads603 Comment 0

3. chinaXiv:201707.00003 [pdf]

知识产权密集型产业现状分析及对策研究—以广东省生物医药行业为例

侯红明; 庞弘燊; 宋亦兵; 覃筱楚; 范风舟; 赵鹏武
Subjects: Biology >> Biomedical Laboratory Science

由于生物医药产业具有相当可观的经济和社会效益,其已经成为许多国家重点发展的朝阳产业。为推动生物医药相关产业的发展,诸如美国、日本、印度等国家把生物技术产业作为了提高本国竞争力的手段,并制定了相应的法律法规规范生物医药产业的发展和保障生物医药的知识产权。本论文首先从宏观层面进行各角度数据分析,包括全球、我国的生物医药产业知识产权发展态势分析,然后以广东省生物医药产业为例,对其知识产权密集型情况指标的数据进行分析,并与其他省份的产业经济和专利情况等指标数据进行对比,最后提出有效提高广东省生物医药产业发展和运用知识产权,增强产业竞争力的对策和建议。

submitted time 2017-07-03 Hits11882Downloads1748 Comment 3

4. chinaXiv:201705.00899 [pdf]

广东省生物医药知识产权密集型产业对比分析研究

侯红明; 庞弘燊; 宋亦兵; 覃筱楚; 黄耀东; 张雯
Subjects: Biology >> Biomedical Laboratory Science

摘要:知识产权密集型产业具备较为明显的专利优势,依赖技术创新与知识产权参与市场摘要:知识产权密集型产业具备较为明显的专利优势,依赖技术创新与知识产权参与市场竞争。生物医药产业具有巨大的经济效益和社会效益,是广东大力扶持的新兴产业。本文选取广东高技术产业、先进制造业及传统产业下的若干产业与生物医药产业进行知识产权密集型情况对比,并通过发展现状、经济贡献及研发创新三个维度进行了对比,最后利用SPSS工具对广东省生物医药专利发展进行预测,为增强广东生物医药知识产权密集型产业竞争力提供建议。

submitted time 2017-05-23 Hits4214Downloads907 Comment 0

5. chinaXiv:201705.00726 [pdf]

Differential expression analysis of Liprin-a2 in hibernating bat (Rhinolophus ferrumequinum)

Lihong Yuan; Xueguo Zuo; Jinping Chen; Benfu Lin; Junpeng Zhang; Min SunShuyi Zhang
Subjects: Biology >> Biomedical Laboratory Science

A PCR-based subtractive hybridization technique was used to identify genes up-regulated in the hibernating bat brain to explore the molecular mechanism of hibernation. Three genes, Liprin-a2, PTP4A2 and CAMKKb were differentially expressed in hibernating bat brain tissue compared to active bat brain tissue. One of them, Liprin-a2, which has recently been shown to have the key function in the organization of presynaptic and postsynaptic multiprotein complexes was studied in detail. We demonstrated that the expression level of Liprin-a2 was up-regulated almost 4-fold in hibernating bat brains by RT-PCR compared to levels in active bats. The differential expression pattern of Liprin-a2 was also detected in muscle, fat, brain and heart tissue of hibernating bats by real-time quantitative PCR. The result indicated that Liprin-a2 was over-expressed in brain and heart tissue and down-regulated in muscle and fat. In brain tissue of hibernating bats, Liprin-a2 expression was statistically significantly higher than in brain tissue of active controls (P = 0.029). The precise control of transcriptional level and the distinctively differential expression pattern of Liprin-a2 in different organs during circannual hibernation may have important physiological significance, not only in maintaining normal function of many key organs but also in effectively conserving limited energy resources without physiological damage.

submitted time 2017-05-10 Hits1875Downloads303 Comment 0

6. chinaXiv:201705.00725 [pdf]

Rapid isothermal detection assay: a probe amplification method for the detection of nucleic acids

Wenjuan Gao; Xiang Li; Lingwen Zeng; Tao Peng(1)
Subjects: Biology >> Biomedical Laboratory Science

Simple, accurate, and stable diagnostic tests are essential to control viral infectious diseases such as avian influenza virus. The current technologies are often inaccessible to people who need them, mainly because of the specialized equipment and the need for highly trained technologists. Here, we describe a rapid isothermal nucleic acid detection assay (RIDA) that can be used to detect both DNA and RNA targets. Using chemically modified probes, we designed a lateral-flow (LF) immunoassay that can be used in combination with RIDA for equipment-free nucleic acid target detection. RIDA is a “probe amplification” assay that uses the single-strand nicking activity of restriction nicking endonucleases to repeatedly cleave synthetic probes hybridizing to the same target sequences. In the RIDA-LF combined assay, chemically labeled probes are covalently conjugated to magnetic microbeads, which is propitious to separate cleaved probes from the reaction solution. The cleaved probes in the solution are then detected with an LF immunoassay. The real-time assay shows that RIDA is able to specifically detect target sequences in 5 to 15 min. The RIDA-LF combined assay can specifically detect nucleic acid targets without sophisticated equipment. In this report, our data suggest that RIDA is a flexible simple assay that could be applied for point-of-care detection. The modified-RIDA described in this report further extends the application of this technology. © 2008 Elsevier Inc. All rights reserved.

submitted time 2017-05-10 Hits1871Downloads314 Comment 0

7. chinaXiv:201705.00724 [pdf]

Aromatic Residues in the C-terminal Domain 2 Are Required for Nanog to Mediate LIF-independent Self-renewal of Mouse Embryonic Stem Cells

Wang, Zhe(1.2); Ma, Tianhua; Chi, Xiaoke; Pei, Duanqing
Subjects: Biology >> Biomedical Laboratory Science

Nanog was identified by its ability to sustain the LIF-independent self-renewal of mouse embryonic stem (ES) cells and has recently been shown to play a role in reprogramming adult fibroblasts into pluripotent stem cells. However, little is known about the structural basis of these remarkable activities of Nanog. We have previously identified an unusually strong transactivator named CD2 at its C terminus. Here we demonstrate that CD2 is required for Nanog to mediate ES cell self-renewal. Furthermore, deletion and point mutation analysis revealed that CD2 relies on at least seven aromatic amino acid residues to generate its potent transactivating activity. A mutant Nanog bearing alanine substitutions for these seven residues fails to confer LIF-independent self-renewal in mouse ES cells. Substitution of CD2 by the viral transactivator VP16 gave rise to Nanog-VP16, which is 10 times more active than wild-type Nanog in ES cells. Surprisingly, the expression of Nanog-VP16 in mouse ES cells induces differentiation and is thus unable to sustain LIF-independent self-renewal for mouse ES cells. Taken together, our results demonstrate that the CD2 domain of Nanog is a unique transactivator that utilizes aromatic residues to confer specific activity absolutely required for ES self-renewal.

submitted time 2017-05-10 Hits2012Downloads301 Comment 0

8. chinaXiv:201705.00723 [pdf]

Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia

Wang, Lan; Zhou, Guang-Biao; Liu, Ping; Song, Jun-Hong; Liang, Yang; Yan, Xiao-Jing; Xu, Fang; Wang, Bing-Shun; Mao, Jian-Hua; Shen, Zhi-Xiang
Subjects: Biology >> Biomedical Laboratory Science

To enhance therapeutic efficacy and reduce adverse effects, practitioners of traditional Chinese medicine (TCM) prescribe a combination of plant species/minerals, called formulae, based on clinical experience. Nearly 100,000 formulae have been recorded, but the working mechanisms of most remain unknown. In trying to address the possible beneficial effects of formulae with current biomedical approaches, we use Realgar-Indigo naturalis formula (RIF), which has been proven to be very effective in treating human acute promyelocytic leukemia (APL) as a model. The main components of RIF are realgar, Indigo naturalis, and Salvia miltiorrhiza, with tetraarsenic tetrasulfide (A), indirubin (I), and tanshinone IIA (T) as major active ingredients, respectively. Here, we report that the ATI combination yields synergy in the treatment of a murine APL model in vivo and in the induction of APL cell differentiation in vitro. ATI causes intensified ubiquitination/degradation of promyelocytic leukemia (PML)-retinoic acid receptor #1; (RAR#1;) oncoprotein, stronger reprogramming of myeloid differentiation regulators, and enhanced G1/G0 arrest in APL cells through hitting multiple targets compared with the effects of mono- or biagents. Furthermore, ATI intensifies the expression of Aquaglyceroporin 9 and facilitates the transportation of A into APL cells, which in turn enhances A-mediated PML-RAR#1; degradation and therapeutic efficacy. Our data also indicate A as the principal component of the formula, whereas T and I serve as adjuvant ingredients. We therefore suggest that dissecting the mode of action of clinically effective formulae at the molecular, cellular, and organism levels may be a good strategy in exploring the value of traditional medicine.

submitted time 2017-05-10 Hits1861Downloads310 Comment 0

9. chinaXiv:201705.00722 [pdf]

Adenoviral cardiotrophin-1 transfer improves survival and early graft function after ischemia and reperfusion in rat small-for-size liver transplantation model

Jun Song(1.2); Ye-Wei Zhang; Ai-Hua Yao; Yue Yu; Zhi-Yuan Hua; Li-Yong PuGuo-Qiang Li; Xiang-Cheng Li; Feng Zhang; Guo-Qing Sheng; Xue-Hao Wang
Subjects: Biology >> Biomedical Laboratory Science

This study was to investigate the effect of donor liver adenoviral cardiotrophin-1 (CT-1) gene transfer on early graft survival and function in rat small-for-size liver transplantation. We constructed a recombinant murine CT-1 adenoviral vector. Donor rats were transduced in vivo with adenoviruses expressing CT-1 (AdCT-1) or control vector (AdEGFP). Livers were harvested 4 days later, reduced to 40% of weight, and transplanted. A syngeneic rat orthotopic liver transplantation model was performed using 40% small-for-size grafts. Graft survival, liver function, hepatic architecture change, the degree of necrosis and apoptosis, and cell survival signaling pathways were assessed. AdCT-1 pretreatment markedly improved liver function and the survival of small-for-size grafts. In the CT-1 treatment group, hepatic architecture was well protected, apoptotic and necrotic cells were reduced; anti-apoptotic protein bcl-2 was up-regulated and proapoptotic cleaved caspase-3 was down-regulated, cell survival signaling pathways were activated by phosphorylation of protein kinase B (Akt), extracellular-regulated kinase (ERK) and Signal transducer and activator of transcription-3 (Stat- 3) after transplantation. In conclusion, donor liver adenoviral CT-1 transfer ameliorated ischemia/reperfusion injury by decreasing hepatic necrosis and apoptosis in small-for-size liver transplantation, mediated in part by activation of the Akt, ERK, and Stat-3 survival signaling pathways. These results may provide a potential clinical strategy to improve the outcome of small-for-size liver grafts.

submitted time 2017-05-10 Hits1693Downloads271 Comment 0

10. chinaXiv:201705.00721 [pdf]

An efficient method for the synthesis of disubstituted thioureas via the reaction of N,N0-di-Boc-substituted thiourea with alkyl and aryl amines under mild conditions

Biaolin Yin; Zhaogui Liu; Mingjun Yi; Jiancun Zhang
Subjects: Biology >> Biomedical Laboratory Science

An efficient method for the synthesis of disubstituted thioureas via the reaction of N,N0-di-Boc-substituted thiourea 5 with alkyl and aryl amines under mild conditions has been developed. In the presence of NaH as a base, trifluoroacetic anhydride (TFAA) reacted with 5 providing intermediate 6, which then reacted with amines giving thioureas 7 in excellent yields. This reaction conditions tolerated other functional groups such as amide, ester, enol ether and hydroxyl groups.

submitted time 2017-05-10 Hits1868Downloads303 Comment 0

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