中国生物医药产业技术创新战略联盟发展思路与对策(英文)

1 Introduction Modern biotechnology has significantly propelledthe development of global economy and has a majorimpact on our life[1-2].According to the report releasedin March 2011 by IMS Health,

Analysis of active patents to investigate the frequency and patterns of Chinese herbal extract combinations claiming to treat heart disease

Objective:Using Chinese patents in force to investigate the frequency and patterns of Chinese herbal extract combinations claiming to treat heart disease.Methods:Patent documents were retrieved from the official website of the State Intellectual Property Office of the People’s Republic China.Cluster,frequency,and fuzzy cluster analyses were applied.Results:A high number of patents in force included high-frequency herbs such as Salvia miltiorrhiza,Panax ginseng,and Panax notoginseng,as well as high-frequency herbal families such as Araliaceae,Leguminosae,Labiatae,and Umbelliferae.Herb pairs such as P.ginsengþOphiopogon japonicus,S.miltiorrhizaþDalbergia odorifera,and P.ginsengþSchisandra chinensis are also commonly used,as well as herbal family pairs such as AraliaceaeþLiliaceae,LauraceaeþLeguminosae,and AraliaceaeþSchisandraceae.Traditional treatment principles for preventing and treating heart diseases was most-commonly based on simultaneously treating the liver and heart and treating the lung and spleen secondarily for choosing herbal combinations.Conclusion:Most of the high-frequency Chinese herbs in the patents investigated belong to the high-frequency herbal families,and herb pairs were commonly selected to coincide with the commonly-used herbal family pairs.Low-frequency Chinese herbs were also used,but generally belonged to the high-frequency herbal families,and were therefore similar to the highfrequency herbs in terms of traditional categories of taste and channel entered.The results reflect the use of traditional principles of formula composition,and suggest that these principles may indeed be an effective guide for further research and development of Chinese herbal extract combinations to prevent and treat heart diseases.

InvasionDB: A genome and gene database of invasive alien species

Invasive alien species(IAS) are species whose introduction to areas outside of their native range cause harm to economics, biodiversity, and the environment. Understanding the genetic basis of invasiveness is critical for preventing invasion by an alien species and managing IAS with eco-friendly control methods. In addition, uncovering the genomic features of IAS is essential for accurately predicting invasiveness. However, even though increasing efforts have been devoted to sequencing the genomes of IAS, there is still not an integrated genome database for the invasive biology community. Here, we first determined a list of invasive plants and animals by mining references and databases. Then, we retrieved the genomic and gene data of these IAS, and constructed a database, Invasion DB. Invasion DB encompasses 131 IAS genomes, 76 annotated IAS assemblies, and links these data to conventional functions such as searching for gene coding sequences and Pfam, KEGG, NR annotations, BLAST server, JBrowse, and downloads services. Next, we analyzed 19 invasivenessrelated gene families which confer invasiveness in insects. To study the roles of noncoding RNA in invasiveness, we also annotated 135 494 mi RNAs, 89 294 r RNAs, and 2 671 941 t RNAs from these IAS. In summary, Invasion DB is useful for studying the invasiveness at the genomic level, and thus helps to develop novel management strategies to control IAS.

BioNano Genome Map Resource for Oryza sativa ssp.japonica and indica and Its Application in Rice Genome Sequence Correction and Gap Filling

Dear Editor As one of the most important staple food crops worldwide, rice is among the first plant species whose genomes were sequenced. The reference genome for Oryza sativa ssp. japonica variety Nipponbare was completed by the International Rice Genome Sequencing Project （IRGSP） using a bacterial artificial chromosome （BAC）-based cloning strategy （Matsumoto et al., 2005）.

Comparison of caspase-3 activation in tumor cells upon treatment of chemotherapeutic drugs using capillary electrophoresis

Caspases play important roles in cell apoptosis.Meas-urement of the dynamics of caspase activation in tumor cells not only facilitates understanding of the molecular mechanisms of apoptosis but also contributes to the development,screening,and evaluation of anticancer drugs that target apoptotic pathways.The fluorescence resonance energy transfer(FRET)technique provides a valuable approach for defining the dynamics of apop-tosis with high spatio-temporal resolution.However,FRET generally functions in the single-cell level and becomes ineffective when applied in the high throughput detection of caspase activation.In the cur-rent study,a FRET sensor was combined with capillary electrophoresis(CE)to achieve a high throughput method for cellular caspase detection.The FRET-based CE system is composed of a homemade CE system and a laser source for detecting the dynamics of caspase-3 in various cells expressing sensors of caspase-3 that have been treated with anticancer drugs,such as cell cycle-independent drug cisplatin and specific cell cycle drugs camptothecin and etoposide,as well as their combination with tumor necrosis factor(TNF).A posi-tive correlation between the caspase-3 activation ve-locity and drug concentration was observed when the cells were treated with cisplatin,but cells induced by camptothecin and etoposide did not show any apparent correlation with their concentrations.Moreover,differ-ent types of cells presented distinct sensitivities under the same drug treatment,and the combination treat-ment of TNF and anticancer drugs significantly accel-erated the caspase-3 activation process.Its high throughput capability and detection sensitivity make the FRET-based CE system a useful tool for investi-gating the mechanisms of anticancer drugs and anti-cancer drug screening.

Biodegradation of pendimethalin by Bacillus subtilis Y3

A bacterium strain Y3,capable of efficiently degrading pendimethalin,was isolated from activated sludge and identified as Bacillus subtilis according to its phenotypic features and 16 S rRNA phylogenetic analysis.This strain could grow on pendimethalin as a sole carbon source and degrade 99.5%of 100 mg/L pendimethalin within 2.5 days in batch liquid culture,demonstrating a greater efficiency than any other reported strains.Three metabolic products,6-aminopendimethalin,5-amino-2-methyl-3-nitroso-4-（pentan-3-ylamino） benzoic acid,and 8-amino-2-ethyl-5-（hydroxymethyl）-1,2-dihydroquinoxaline-6-carboxylic acid,were identified by HPLC-MS/MS,and a new microbial degradation pathway was proposed.A nitroreductase catalyzing nitroreduction of pendimethalin to 6-aminopendimethalin was detected in the cell lysate of strain Y3.The cofactor was nicotinamide adenine dinucleotide phosphate（NADPH） or more preferably nicotinamide adenine dinucleotide（NADH）.The optimal temperature and pH for the nitroreductase were 30℃ and 7.5,respectively.Hg^（2＋）,Ni^（2＋）,Pb^（2＋）,Co^（2＋）,Mn^（2＋） Cu^（2＋）,Ag~＋,and EDTA severely inhibited the nitroreductase activity,whereas Fe^（2＋）,Mg^（2＋）,and Ca^（2＋） enhanced it.This study provides an efficient pendimethalin-degrading microorganism and broadens the knowledge of the microbial degradation pathway of pendimethalin.

Perspectives on the management of synthetic biological and gene edited foods

Synthetic biology,gene editing and transgene technologies that involving gene manipulation are widely used in food research and development.In recent decades,China has formulatedmany policies and regulations to govern the safety of genetically modified agricultural organisms.Based on the comparative analysis of technical connotations on synthetic biology,gene editing and transgenes and related risksregarding the safety of food,environment and the management of genetically modified agricultural organisms,this paper puts forward the following suggestions on 1)management of synthetic biological and gene-edited foods(in this paper,“food”refers to“edible agricultural products and food”),2)promoting the gradual process of industrialization on gene-edited and synthetic biological foods through lessons learned from the practice on genetically modified crops,3)speeding up the industrialization of gene-edited foods and prudently promoting the application of synthetic biological foods,4)urgently establishing and updating policies and regulations related to gene-edited and synthetic biological foods,5)unifying the legislation and supervision of synthetic biological,gene-edited and genetically modified foods 6)establishing ethical principles and bottom lines for genetically manipulated foods.

In silico Analysis of the Potential Infection Mechanisms of Magnaporthe grisea from Horizontal Gene Transfer Hypothesis

Horizontal gene transfer （HGT） has long been considered as a principal force for an organism to gain novel genes in genome evolution. Homology search, phylogenetic analysis and nucleotide composition analysis are three major objective approaches to arguably determine the occurrence and directionality of HGT. Here, 21 genes that possess the potential to horizontal transfer were acquired from the whole genome of Magnaporthe grisea according to annotation, among which three candidate genes （corresponding protein accession numbers are EAA55123, EAA47200 and EAA52136） were selected for further analysis. According to BLAST homology results, we subsequently conducted phylogenetic analysis of the three candidate HGT genes. Moreover, nucleotide composition analysis was conducted to further validate these HGTs. In addition, the functions of the three candidate genes were searched in COG database. Consequently, we conclude that the gene encoding protein EAA55123 is transferred from Clostridium perfringens. Another HGT event is between EAA52136 and a certain metazoan＇s corresponding gene, but the direction remains uncertain. Yet, EAA47200 is not a transferred gene.

Epidermal growth factor receptor stabilizes programmed death ligand 1 by glycosylation in colorectal cancer with microstatellite instability status

Programmed death ligand-1(PD-L1)is involved in inhibiting of T lymphocyte proliferation,producing cytokine,cytolytic activity,and suppressing of the immune response.Genes with molecular alterations involved in DNA mismatch repair promote cancer initiation and tumor progression.Clinical studies show that colorectal cancer(CRC)patients harboring microsatellite instability(MSI)have a higher anti-programmed cell death protein 1/PD-L1 immunotherapy response ratio compared with microsatellite stable subgroup patients.The underlying mechanism has however remained unclear.Here,we found that compared with microsatellite stable samples,PD-L1 was glycosylated and highly expressed both in MSI CRC cell lines and tissue samples.Specifically,PD-L1 was Nglycosylated at its N35,N192,N200,and N219 sites,and the four glycosylation sites were all responsible for PD-L1 degradation.Additionally,non-glycosylated PD-L1 underwent rapid degradation compared with glycosylated PD-L1 through the 26S proteasome pathway.The faster degradation of the non-glycosylated PD-L1 was ascribed to its binding to glycogen synthase kinase 3b via ubiquitination.This degradation phenotype was,however,not observed for glycosylated PD-L1.Significantly,glycosylated PD-L1 was up-regulated by activated epidermal growth factor receptor in MSI CRC cells.Together,our results indicate that epidermal growth factor receptor stabilized PD-L1 via glycosylation in MSI CRC cells,uncovering a novel role of PD-L1 in MSI CRC immunosuppression and disease progression.The study was approved by the Clinical Ethics Review Committee at the Six Affiliated Hospital of Sun Yat-sen University,China(Approval No.2019ZSLYEC-005).