Subjects: Biology >> Biophysics >> Oncology submitted time 2016-05-11
Wang, Anxin
Chen, Lisha
Li, Chunlin
Zhu, Yimin
Wang, Anxin
Chen, Lisha
Li, Chunlin
Wang, Anxin
Chen, Lisha
Li, Chunlin
Abstract： Accumulating evidence suggests that cancer stem cells (CSCs) are heterogeneous populations and their phenotypes are unstable. A number of intrinsic and extrinsic mechanisms contribute to CSC phenotypic variation. The existence of various CSC subpopulations which would lead to a rapid relapse after primary treatments might pose a problem for CSC targeted therapeutics. In order to develop more effective approaches to cancer therapeutics, more CSC-related surface markers or targeting molecules, as well as some novel targeting strategies should be explored. This review summarized the origin and performance of heterogeneity in CSCs and discussed their therapeutic implications. (c) 2014 Elsevier Ireland Ltd. All rights reserved.
Peer Review Status:
Awaiting Review
Subjects: Biology >> Virology submitted time 2020-02-14
Abstract： Abstract: In 2019, the 2019 novel Coronavirus (2019-nCoV) has caused the pneumonia outbreak in Wuhan (a city of China). In our previous study, the analytical results showed that both 2019-nCoV and SARS coronavirus belongs to Betacoronavirus subgroup B (BB coronavirus), but have large differences. The most important finding was that the alternative translation of Nankai CDS could produce more than 17 putative proteins, which may be responsible for the host adaption. The genotyping of 13 viruses using the 17 putative proteins revealed the high mutation rate and diversity of betacoronavirus. The present study for the first time reported a very important mutation in the Spike (S) proteins of BB coronavirus. By this mutation, 2019-nCoV acquired a cleavage site for furin enzyme, which is not present in the S proteins of all other BB coronavirus (e.g. SARS coronavirus) except the Mouse Hepatitis coronavirus (MHV). This mutation may increase the efficiency of virus infection into cells, making 2019-nCoV has significantly stronger transmissibility than SARS coronavirus. Because of this mutation, the packing mechanism of the 2019-nCoV may be changed to being more similar to those of MHV, HIV, Ebola virus (EBoV) and some avian influenza viruses, other than those of all other BB coronavirus (e.g. SARS coronavirus) except the Mouse Hepatitis coronavirus (MHV). In addition, we unexpectedly found that some avian influenza viruses acquired a cleavage site for furin enzyme by mutation as 2019-nCoV. Further studies of this mutation will help to reveal the stronger transmissibility of 2019-nCoV and lay foundations for vaccine development and drug design of, but not limited to 2019-nCoV.
Peer Review Status:Awaiting Review
Subjects: Biology >> Bioengineering submitted time 2018-12-25 Cooperative journals: 《中国生物工程杂志》
Abstract：通过现代生物技术制成的DNA疫苗、重组疫苗和亚单位疫苗等新型疫苗，虽然安全性较传统疫苗有所提高，但其免疫原性不及传统疫苗，需要通过佐剂增强疫苗的免疫效力。随着对佐剂研究的不断深入，铝佐剂、油乳佐剂、微生物类佐剂、蜂胶佐剂、左旋咪唑佐剂、脂质体佐剂、中药佐剂及小肽类佐剂等相继问世，其作用机理也随研究的不断深入逐渐清晰。通过动物免疫实验结果发现，小肽类免疫佐剂不仅可以增强特异性免疫反应，具备免疫增强剂的功效，而且获取简单，便于运输保存，安全性高，可能是未来佐剂研究的一个主要方向。
Subjects: Biology >> Bioengineering Subjects: Engineering and technical science >> Bioengineering submitted time 2018-12-11
Abstract： Carbon dioxide partial pressure (pCO2) is an important parameter in mammalian cell culture, which come from cell respiration, bicarbonate in culture media and CO2 added during culture for pH maintenance. Generally, pCO2 is not precisely controlled like pH in cell culture, but it is crucial to maintain pCO2 level within a reasonable range, usually ranging from 30 to 80 mmHg. Higher (> 80mmHg) or lower (< 30mmHg) pCO2 levels were reported to be detrimental to cell growth, metabolism, productivity and product quality. Higher pCO2 is always encountered during scale-up, especially for the high density perfusion culture. Therefore, pCO2 difference between small scale (< 15 L) and large scale (> 200L) needs to be considered. This review illustrates the effects of pCO2 on cell growth, metabolism, productivity and product quality. In addition, the approaches to control pCO2 during scale-up are also discussed. " "
Peer Review Status:Awaiting Review
Subjects: Biology >> Virology submitted time 2020-02-25
Xia, Jia
Lu, Guoliang
Lu, Jing
Zhang, Jiahui
Feng, Lin
Wang, Bing
Yu, Hang
Xu, Yingjie
Lin, Jinzhong
Abstract： Frequent outbreaks of coronavirus make the development of an effective vaccine imperative. Recently, vaccines based on in-vitro transcribed messenger RNA (mRNA) have shown great potential. The streamlined manufacturing of mRNA molecules, combined with the superior flexibility in the antigen screening, greatly accelerates the development process. When using an mRNA platform to develop a vaccine, initial antigen choice plays a crucial role in determining the final efficacy and safety of the vaccine. Furthermore, mRNA sequences that encode antigens require extensive optimization to ensure highly efficient and sustained expression. Our ongoing efforts to develop an effective mRNA vaccine against 2019-nCoV place emphasis on the virus-like particles (VLPs) as the presenting antigen. At the same time, our second fast track uses mRNA to express the receptor-binding domain of the spike protein(S-RBD). After extensive optimization, an mRNA cocktail containing three genes is able to produce 2019-nCoV virus-like particles highly similar to the native 2019-nCoV. Meanwhile, an mRNA vaccine candidate expressing S-RBD is being tested in mice for its immunogenicity. We will next compare both the efficacy and the safety of the two mRNA vaccines based on S-RBD and VLPs, respectively.
Peer Review Status:Awaiting Review
Subjects: Biology >> Virology Subjects: Computer Science >> Other Disciplines of Computer Science submitted time 2020-02-21
Abstract： During the outbreak of new infectious diseases, there is an urgent need to put forward scientific hypotheses for the efficacy, mechanism and side effects of candidate drugs. The research and development of vaccines or new drugs need a certain period of time, so the strategy of drug repositioning has its place. However, the clinical data of pathogen and host response of new diseases are not ready, restricts the hypothesis of candidate drugs. At this stage, we often try to use broad-spectrum antiviral drugs according to the clinical characteristics of patients. In this paper, we propose a new method aCODE (agile discovery method of drugs or natural products for emerging epidemic) which based on the heuristic search strategy widely used in the field of artificial intelligence. Based on the broad-spectrum antiviral drugs with some early efficacy tips, the host target protein collection is obtained, and the associated gene modules is searched on the whole genome scale. We then carry out pattern matching and statistics for candidate compounds (such as approved drugs and natural products ingredients). This method can update the input drugs according to the progress of clinical practice, and output more accurate results iteratively. The output components from natural products, traditional Chinese medicine or food can be used for quick trial to form a closed loop of agile R & D test. In addition, for the second update of this method and its comparison with literature evidence, please refer to: http://chinaxiv.org/abs/202002.00024.
Peer Review Status:Awaiting Review
Subjects: Biology >> Bioengineering submitted time 2018-02-11 Cooperative journals: 《中国生物工程杂志》
Abstract：目的：制备负载NGF的可注射壳聚糖透明质酸复合水凝胶，探讨其理化性能以及生物相容性。方法：首先京尼平交联制备壳聚糖透明质酸复合水凝胶材料，采用倒置法检测凝胶时间；扫描电镜观察材料形态结构；NGF释放实验、体外溶胀以及降解实验等检测凝胶材料的物理化学性能；通过MTT实验、NGF活性检测、材料与细胞共培养检测凝胶材料生物学性能。结果：在37℃条件下，可注射凝胶材料凝胶时间在37min左右，凝胶材料为多孔网络状结构，凝胶材料8周最多能够降解76％，缓释21天的NGF具有生物活性，凝胶材料能促进RSC96细胞的粘附、增殖、迁移以及细胞活性物质的释放。结论：京尼平交联的壳聚糖透明质酸水凝胶具有良好的生物相容性，能作为NGF的载体材料，具有成为神经导管内填充材料的潜能。
Subjects: Biology >> Botany >> Plant cytology, plant genetics & plant morphology submitted time 2016-05-04
Abstract：
Fe deficiency is a widespread nutritional disorder in plants. The basic helix-loop-helix (bHLH) transcription factors (TFs), especially Ib subgroup bHLH TFs which are involved in iron uptake, have been identified. In this study, an IVc subgroup bHLH TF MdbHLH104 was identified and characterized as a key component in the response to Fe deficiency in apple. The overexpression of the MdbHLH104 gene noticeably increased the H+-ATPase activity under iron limitation conditions and the tolerance to Fe deficiency in transgenic apple plants and calli. Further investigation showed that MdbHLH104 proteins bonded directly to the promoter of the MdAHA8 gene, thereby positively regulating its expression, the plasma membrane (PM) H+-ATPase activity and Fe uptake. Similarly, MdbHLH104 directly modulated the expression of three Fe-responsive bHLH genes, MdbHLH38, MdbHLH39 and MdPYE. In addition, MdbHLH104 interacted with 5 other IVc subgroup bHLH proteins to coregulate the expression of the MdAHA8 gene, the activity of PM H+-ATPase and the content of Fe in apple calli. Therefore, MdbHLH104 acts together with other apple bHLH TFs to regulate Fe uptake by modulating the expression of the MdAHA8 gene and the activity of PM H+-ATPase in apple.
Peer Review Status:Awaiting Review
Subjects: Biology >> Bioengineering submitted time 2018-01-15 Cooperative journals: 《中国生物工程杂志》
Abstract：目的：从产品开发角度分析寡核苷酸类药物的发展现状和未来趋势。方法：检索科睿唯安（Clarivate Analytics）的Cortellis数据库的数据，利用定量分析法和对比分析法对检索结果进行分析。结果：目前已有7种寡核苷酸类药物上市，4种寡核苷酸类药物处于预注册及16种处于临床Ⅲ期，未来市场上的寡核苷酸类药物将呈现快速增长趋势。此外，寡核苷酸类药物的商业交易也越来越多，目前共发生包括药物开发及商业化许可、专利资产出售以及早期药物研发合作等10余起交易，其中药物开发及商业化许可是最主要的交易模式。结论：虽然寡核苷酸类药物市场尚处于起步阶段，但随着未来技术的不断发展改进，相信未来有更多的寡核苷酸类药物上市，为癌症及其他疾病的治疗提供新的契机。
Subjects: Biology >> Bioengineering submitted time 2018-01-16 Cooperative journals: 《中国生物工程杂志》
Abstract：SUMO蛋白酶（Ulp1）是切割小分子泛素修饰（SUMO）融合蛋白获得天然N端靶蛋白的一种工具酶，具有酶切效率高，特异性好等优点。但现有市售SUMO蛋白酶Ulp1价格昂贵，操作复杂，限制了SUMO融合体系的运用。利用基因工程技术，合成基因ulp1（Leu403-Lys621），并在N端和C端加入多聚组氨酸标签（His6），构建重组表达载体psvT7-ulp1，将重组质粒转入大肠杆菌BL21(DE3)和BL21 trxB(DE3)中。经过高通量筛选技术快速确定最优的表达条件为采用BL21(DE3)作为表达宿主，转接后7 h加入IPTG，IPTG的终浓度为0.1 mmol/L，诱导时间为16 h，最终蛋白表达量占菌体总蛋白的34.5%，重组蛋白Ulp1的表达量为190mg/L，通过Ni-NTA一步纯化即可得到纯度95%以上的Ulp1。通过酶切反应，测定酶活为5.19 U/μl，比酶活为5.23×104 U/mg，是先前报道比酶活的1.87倍，通过酶活动力学分析，Ulp1的表观米氏常数 Km=0.359 g/L，Vm=5.10μg/(mL·min)。将SUMO融合表达体系用于单链抗体（Single-Chain Antibody Fragment，scFv）的表达，得到可溶的SUMO-scFv融合蛋白，使用表达的Ulp1进行酶切并纯化，获得纯度高于90%且N端不含多余氨基酸的scFv,操作步骤简单，显著改善了scFv在大肠杆菌中难于高效可溶性表达纯化的现状。
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology submitted time 2016-05-12
Abstract： With the rapid development of high-throughput sequencing technologies, the emerging of methylated RNA immunoprecipitation sequencing (MeRIP-seq) technology makes it possible to detect RNA epigenetic modifications in a large scale, which allows transcriptome-wide profiling of RNA methylation. Mining the patterns of global mRNA methylation from these MeRIP-seq data can help reveal the potential functional roles of these mRNA methylations in regulating gene expression, splicing, RNA editing and RNA stability, effectively guiding the therapeutic intervention of cancer. Here, the principle of MeRIP-seq sequencing was first introduced. Then, the recent progress of the processing and analysis of MeRIP-seq data were comprehensively discussed. In the end, the computational problems and challenges faced in the process of MeRIP-seq data processing were also summarized.
Peer Review Status:Awaiting Review
Subjects: Biology >> Virology submitted time 2020-03-06
Abstract： Global emergencies caused by the zoonotic severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and the newly discovered 2019 novel coronavirus (2019-nCoV) have posed a serious threat to human health. The spike (S) glycoprotein, a homotrimer located on the surface of the viral envelope, is the key antigen for therapeutic development. The S2 subunit from the S glycoprotein, which is highly conserved among coronaviruses, contributes to viral entry by mediating the host-viral membrane fusion. However, the structural information of the post-fusion S2 machinery from these highly pathogenic human-infecting coronaviruses is still lacking. Here, we report the structure of SARS-CoV S glycoprotein in the post-fusion state by single particle cryo-electron microscopy, revealing a more rotated HR1-HR2 six-helix bundle and a tightly bound linker region upstream of the HR2 motif that plays an important role in membrane fusion. Comparison with the structure of pre-fusion SARS-CoV S glycoprotein shows dramatic structural rearrangements and conformational changes, resembling that of the Mouse hepatitis virus (MHV) and other class I viral fusion proteins. By analyzing the structural features, describing the glycan shield and mapping the antibody and inhibitor targets on the surface of the post-fusion S glycoprotein, we provide structural basis of potential therapeutic targets within the highly conserved S2 subunit, which may help the development of effective vaccines and therapies against a wide range of SARS-like coronaviruses. " "
Peer Review Status:Awaiting Review
Subjects: Biology >> Bioengineering submitted time 2018-07-31 Cooperative journals: 《中国生物工程杂志》
Abstract：目的：从产品开发角度分析免疫细胞治疗类药物的发展现状和未来趋势。方法：检索科睿唯安（Clarivate Analytics）的Cortellis数据库的数据，利用定量分析法和对比分析法对检索结果进行分析。结果：目前已有2种免疫细胞治疗类药物上市，1种免疫细胞治疗类药物处于预注册阶段，4种药物处于临床III期，同时大量处于临床II/I期药物显示未来市场上将有更多免疫细胞治疗类药物。产品交易方面，目前在免疫细胞治疗类药物的商业交易也趋向频繁。目前已发生的交易中，本文列举分析了交易金额前十的交易，其中药物开发及商业化许可是最主要的交易模式。结论：目前免疫细胞治疗类药物市场尚处于起步阶段，但随着未来技术的不断发展改进，相信未来有更多的药物进入商用市场，为癌症及其他疾病的治疗提供新的契机。
Subjects: Biology >> Bioengineering submitted time 2018-04-19 Cooperative journals: 《中国生物工程杂志》
Abstract：SpyCatcher和SpyTag可通过自发反应形成共价键，产生稳定的分子自组装体。酶分子自组装体因具有高效有序的催化特性在合成生物学和纳米技术领域具有重要的应用价值。为探索SpyTag/SpyCatcher在大肠杆菌胞内多酶复合体系形成有序自组装分子能力，将SpyCatcher和SpyTag分别与P450BM3m单加氧酶和葡萄糖脱氢酶GDH进行融合表达，以期产生具有辅酶再生循环系统、高效生物合成靛蓝分子的SpyTag/SpyCatcher双酶自组装复合体。首先，通过电泳及质谱对重组工程菌表达蛋白进行分析，证实SpyCatcher-P450BM3m与SpyTag-GDH在胞内成功形成了自组装多酶复合体；然后，系统分析了不同培养条件下组装体合成靛蓝的能力，结果发现，经0.5mmol/L IPTG诱导后，菌体在16 ℃继续培养18 h后，工程菌对吲哚（2 mmol/L）与葡萄糖（4 mmol/L）的全细胞催化能力最强，靛蓝产量最高达258 mg/L，是未组装多酶系统的1.9倍，比P450BM3m单酶表达系统高约2.4倍；反应70 min后达到反应平衡，转化率为52%。本研究成功实现了SpyTag/SpyCatcher介导的多酶体系在大肠杆菌细胞中的自组装和高效转化体系，为胞内多酶复合物组装体的设计提供了新思路。
Subjects: Biology >> Bioengineering submitted time 2017-07-24 Cooperative journals: 《中国生物工程杂志》
Abstract： Development Status and Trend Analysis of Mesenchymal Stem Cells Therapeutic Products
Subjects: Biology >> Bioengineering submitted time 2018-04-19 Cooperative journals: 《中国生物工程杂志》
Abstract：CRISPR/Cas9系统已不仅仅是一种革命性的基因编辑工具，还能在各种原核和真核生物中调控基因转录。近年来，由CRISPR/Cas9衍生而来的CRISPR-dCas9系统已被用于基因成像、高通量筛选、基因调控、必需基因功能研究及表观遗传调控等多个方向。本文总结了近年来CRISPR-dCas9系统在激活或抑制基因转录、降低脱靶效率、sgRNA与转录强度及特异性之间的联系等方面的研究进展，以期对CRISPR-dCas9系统定向调控基因转录的研究提供参考和帮助，并就其未来可能的改进进行了展望。
Subjects: Biology >> Botany >> Applied botany submitted time 2020-05-28 Cooperative journals: 《广西植物》
Abstract： Magnolia officinalis is a famous traditional medicinal plant, belonging to the Magnoliaceae family and Magnolia genus and being widely cultivated in China. Its bark, root bark, branch bark, leaves, flowers and fruits could be used as medicine or food. However, the whose genome information is little known for this plant species. In order to obtain the whole genome sequence information of M. officinalis, the leaf DNA was used as the material, and the third-generation sequencing technology of Pacbio Sequel was used to establish its nucleotide sequence database. Then genome assembly, function annotation and evolution analysis were carried out by bioinformatic methods. The experimental results showed that 140.91 Gb third-generation data were obtained after the original sequencing data, with the Read N50 about 13 784 bp. The assembled M. officinalis genome size was 1.68 Gb, Contig N50 being about 222 069 bp, and the integrity of single copy gene being 78.05 %. 98.40% of the genes from the assembled sequence got gene annotation after being compared with functional databases such as NR, KOG and KEGG. The result of KOG gene annotation was that the protein function of M. officinalis concentrated in the general functional prediction only, posttranslational modification, protein turnover, chaperones signal transduction mechanisms. GO functional classification indicated that the genes of M. officinalis concentrated on cell components and biological processes. KEGG analysis found that the M. Officinalis genes mostly involved in metabolic pathways. By comparative genomics analysis, the genomes of Vitis vinifera, Arabidopsis thaliana, Oryza sativa, Poplar trichocarpa, Ginkgo biloba, Amborella trichopoda, Camellia sinensis and Cinnamomum kanehirae were aligned. It was found that 20 801 of 23 424 genes in M. officinalis could be classified into 12 129 families, 515 gene families being unique to M. officinalis. The genetic evolution tree constructed from the genomes of the selected reference species pointed that the M. officinalis (Magnoliaceae) was closely related to Cinnamomum kanehirae (Lauraceae), and the divergence time between the two species was about 122.5 mya. It is the first time to use the third-generation sequencing technology to analyze the whole genome of M. officinalis in the study. The study is conducive to its further development and utilization, and also provides the information for the study of the whole genome of other medicinal plants.
Subjects: Biology >> Virology submitted time 2020-04-19
Shu, Ting
Huang, Muhan
Wu, Di
Ren, Yujie
Zhang, Xueyi
Han, Yang
Mu, Jingfang
Wang, Ruibing
Qiu, Yang
Zhang, Ding-Yu
Zhou, Xi
Abstract： "
Peer Review Status:Awaiting Review
Subjects: Biology >> Bioengineering submitted time 2018-07-15 Cooperative journals: 《中国生物工程杂志》
Abstract：脐带间充质干细胞来源于人体脐带组织，具有自我复制更新和多向分化潜能，是一种具有许多优势的干细胞类型，可用于治疗老年性退变、帕金森、血管缺血、小儿自闭症、系统性红斑狼疮、强直性脊柱炎、多发性神经硬化症、糖尿病、各种创伤、移植物抗宿主病等常规治疗方法难以治愈的疾病，并且治疗效果明确。本文介绍了脐带间充质干细胞的研究发现历程，临床应用价值，分离制备和检测鉴定方法，生物学特性以及规模化生产技术。需要强调的是，脐带间充质干细胞具有比其他一些干细胞（如脐带造血干细胞、骨髓造血干细胞、骨髓间充质干细胞等）没有的优势，材料来源广泛，细胞增殖能力强，没有伦理问题。脐带间充质干细胞的生产和应用应遵循政府或机构颁布的相关法律法规和标准规范。
Subjects: Biology >> Bioengineering submitted time 2018-10-09 Cooperative journals: 《中国生物工程杂志》
Abstract：乙型肝炎病毒(hepatitis B virus，HBV)是引起病毒性乙型肝炎的主要病原体，依然是影响人类健康的全球性问题。干扰素和核苷（酸）类似物是国内外获批上市的主要抗乙肝病毒药物。替诺福韦和恩替卡韦在国外抗乙肝病毒药物市场上占据巨大的份额，而早期推出的拉米夫定和阿德福韦酯因其耐受性和安全性等原因所占市场份额逐年减少。国外有39种抗乙肝病毒新药正处于临床阶段。国内临床上使用更多的是口服核苷(酸)类似药物，尤其是恩替卡韦近年来占近一半抗乙肝药物市场。抗乙肝病毒药物城市零售前10的企业市场份额占整个零售的91.8%，市场集中度较高。虽然国内乙肝新药研发水平与欧美还存在较大差距，但是在国内创新政策推动下，出现了东阳光、正大天晴等20余家从事研发企业，并取得一定的成效。基于我国抗乙肝病毒药物发展困境，提出了继续完善抗乙肝病毒药物医保政策、部署和实施乙型肝炎重大专项等研发项目、推进产学研用深度融合等对策建议。
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