Biotechnology Journal最新文献

{"title":"Lactobacillus reuteri Assists Engineered Bacteria That Target Tumors to Release PD-L1nb to Mitigate the Adverse Effects of Breast Cancer Immunotherapy","authors":"Lijun Yue,&nbsp;Feng Geng,&nbsp;Jiayi Jin,&nbsp;Wenzhen Li,&nbsp;Ben Liu,&nbsp;Maoru Du,&nbsp;Xue Gao,&nbsp;Junhong Lü,&nbsp;Xiaohong Pan","doi":"10.1002/biot.202400428","DOIUrl":"10.1002/biot.202400428","url":null,"abstract":"<div>\u0000 \u0000 <p>Programmed death protein-ligand 1 (PD-L1) inhibitors demonstrate significant antitumor efficacy by modulating T-cell activity and inhibiting the PD-1/PD-L1 pathway, thus enhancing immune responses. Despite their robust effects, systemic administration of these inhibitors is linked to severe immune toxicity. To address this issue, we engineered a strain, REP, which releases PD-L1 nanoantibodies (PD-L1nb) to treat breast cancer and attenuate immunotherapy-related side effects. REP selectively targets tumors and periodically releases PD-L1nb within tumors via a quorum-sensing lysis system. Administration of 10⁸ colony-forming units (CFU) of REP led to a substantial 52% reduction in tumor growth, achieved through the sustained release of PD-L1nb. Importantly, there were no detectable lesions in other organs, with the exception of mild intestinal damage. Further, we explored the potential of a combined treatment using <i>Lactobacillus reuteri</i> (LR) and REP to alleviate intestinal inflammation. LR modulates the expression of inflammatory markers IL-1β, IL-6, and IL-10 through the JNK pathway, reducing intestinal inflammation without compromising REP's antitumor efficacy. Consequently, we formulated a dual strategy employing an engineered strain and probiotics to reduce the adverse effects of immunotherapy in cancer treatment.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"19 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptable Manufacturing and Biofabrication of Milliscale Organ Chips With Perfusable Vascular Beds","authors":"Charles Ethan Byrne,&nbsp;Ashley T. Martier,&nbsp;Gideon Wills Kpeli,&nbsp;Kevin Michael Conrad,&nbsp;William Bralower,&nbsp;Elisabet Olsen,&nbsp;Gabrielle Fortes,&nbsp;Caroline C. Culp,&nbsp;Max Wendell,&nbsp;Keefer A. Boone,&nbsp;Matthew R. Burow,&nbsp;Mark J. Mondrinos","doi":"10.1002/biot.202400550","DOIUrl":"10.1002/biot.202400550","url":null,"abstract":"<p>Microphysiological systems (MPS) containing perfusable vascular beds unlock the ability to model tissue-scale elements of vascular physiology and disease in vitro. Access to inexpensive stereolithography (SLA) 3D printers now enables benchtop fabrication of polydimethylsiloxane (PDMS) organ chips, eliminating the need for cleanroom access and microfabrication expertise, and can facilitate broader adoption of MPS approaches in preclinical research. Rapid prototyping of organ chip mold designs accelerates the processes of design, testing, and iteration, but geometric distortion and surface roughness of SLA resin prints can impede the development of standardizable manufacturing workflows. This study reports postprocessing procedures for manufacturing SLA-printed molds that produce fully cured, flat, patently bonded, and optically clear polydimethyl siloxane (PDMS) organ chips. Injection loading tests were conducted to identify milliscale membrane-free organ chip (MFOC) designs that allowed reproducible device loading by target end-users, a key requirement for broad nonexpert adoption in preclinical research. The optimized milliscale MFOC design was used to develop tissue engineering protocols for (i) driving bulk tissue vasculogenesis in MFOC, and (ii) seeding the bulk tissue interfaces with a confluent endothelium to stimulate self-assembly of perfusable anastomoses with the internal vasculature. Comparison of rocker- and pump-based protocols for flow-conditioning of anastomosed vascular beds revealed that continuous pump-driven flow is required for reproducible barrier maturation throughout the 3D tissue bulk. Demonstrated applications include nanoparticle perfusion and engineering perfusable tumor vasculature. These easily adaptable methods for designing and fabricating vascularized microphysiological systems can accelerate their adoption in a diverse range of preclinical laboratory settings.</p>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"19 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering VIGS Vectors by Modifying Movement Proteins of the 30K Family","authors":"David Villar-Álvarez,&nbsp;José A. Navarro,&nbsp;Vicente Pallas,&nbsp;Jesús Ángel Sanchez-Navarro","doi":"10.1002/biot.202400584","DOIUrl":"10.1002/biot.202400584","url":null,"abstract":"<p>Virus-induced gene silencing (VIGS) represents a particularly relevant tool in agricultural species for studying gene functionality. This study presents a novel approach for utilizing viruses belonging to the 30K family of movement proteins (MPs) as VIGS vectors. The method described here employs smaller inserts (54 bp or less) than those commonly used (100–500 bp). The developed strategy involves modifying 30K family MPs to introduce heterologous sequences of the gene of interest into their coding sequence. This approach enabled the successful induction of gene silencing in <i>Nicotiana tabacum</i> and <i>Nicotiana benthamiana</i>. Three representative viruses of the MP 30K family, alfalfa mosaic virus (AMV), cucumber mosaic virus (CMV), and tobacco mosaic virus (TMV) were employed. The capacity to induce gene silencing of small inserts (18–54 bp) was investigated, enabling to establish a correlation between insert size and silencing efficacy. This allowed the system to be calibrated to achieve partial silencing levels. The relationship between viral encapsidation and the level of gene silencing was also investigated, revealing that a high efficiency of viral encapsidation results in a reduction in the level of gene silencing achieved. Considering these findings, it can be concluded that the approach carried out with AMV, CMV, and TMV could be applied to other members of the MP 30K family. The MP 30K family comprises 20 viral genera and over 500 viral species, which can infect all agronomically significant plant species. Consequently, the strategy presented in this work could be applied to a wide range of relevant hosts.</p>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"19 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GOLPH3-STIP1 Complex Activates STAT3 Through Exosome Secretion to Induce Colon Cancer Metastasis","authors":"Yanta Guo,&nbsp;Zhongshi Hong,&nbsp;Sifu Huang,&nbsp;Yuze Wu,&nbsp;Chengzhi Qiu,&nbsp;Jianhua Xu","doi":"10.1002/biot.202400563","DOIUrl":"10.1002/biot.202400563","url":null,"abstract":"<div>\u0000 \u0000 <p>With a high mortality rate, colon cancer (CC) is the third most common malignant tumor worldwide. The primary causes are thought to be the high invasiveness and migration of CC cells. The functions of Golgi phosphoprotein 3 (GOLPH3), stress-induced phosphoprotein 1 (STIP1), and the signal transducer and activator of transcription 3 (STAT3) signaling pathway in the invasion and migration of CC cells were examined in this study. We collected the exosomes by high-speed centrifugation. The expressions of GOLPH3, STIP1, and epithelial-mesenchymal transition (EMT)-related proteins in CC tissues, cells, and exosomes were analyzed using Western blotting (WB) experiments. The abilities of CC cell invasion and migration were evaluated by the Transwell assay. The binding relationship between GOLPH3 and STIP1 was validated through Co-immunoprecipitation (Co-IP), and their sublocalization in CC cells was determined by immunofluorescence detection under laser confocal microscopy. Immunohistochemistry (IHC) experiments detected the expression levels of each protein in the transplanted tumor mass. Animal experiments confirmed the impact of the GOLPH3/STIP1/STAT3 regulatory axis on CC growth. We found that in CC tissues and cells, GOLPH3 was highly expressed, and silencing GOLPH3 not only greatly reduced CC cell invasion and migration but also prevented EMT. Furthermore, GOLPH3 and STIP1 interacted in CC cells, and the GOLPH3-STIP1 complex affected the capacity for cell invasion and migration by triggering the STAT3 signaling pathway. Noteworthily, GOLPH3, and STIP1 could also be detected in CC cell exosomes, and the exosomes carried the GOLPH3-ST1P1 complex to act on CC cells to activate intracellular STAT3 signaling, ultimately affecting the cancer cell migration and invasion. The above molecular regulatory mechanisms have also been validated in mice. In conclusion, the GOLPH3-STIP1 complex acted on surrounding CC cells through exosomes and activated the STAT3 signaling pathway to stimulate CC cell invasion and migration.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"19 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in Plant Gene Editing Technology: From Construct Design to Enhanced Transformation Efficiency","authors":"Pu Yuan,&nbsp;Muhammad Usman,&nbsp;Wenshan Liu,&nbsp;Ashna Adhikari,&nbsp;Chunquan Zhang,&nbsp;Victor Njiti,&nbsp;Ye Xia","doi":"10.1002/biot.202400457","DOIUrl":"10.1002/biot.202400457","url":null,"abstract":"<p>Plant gene editing technology has significantly advanced in recent years, thereby transforming both biotechnological research and agricultural practices. This review provides a comprehensive summary of recent advancements in this rapidly evolving field, showcasing significant discoveries from improved transformation efficiency to advanced construct design. The primary focus is on the maturation of the Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas)9 system, which has emerged as a powerful tool for precise gene editing in plants. Through a detailed exploration, we elucidate the intricacies of integrating genetic modifications into plant genomes, shedding light on transport mechanisms, transformation techniques, and optimization strategies specific to CRISPR constructs. Furthermore, we explore the initiatives aimed at extending the frontiers of gene editing to nonmodel plant species, showcasing the growing scope of this technology. Overall, this comprehensive review highlights the significant impact of recent advancements in plant gene editing, illuminating its transformative potential in driving agricultural innovation and biotechnological progress.</p>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"19 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biot.202400457","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visualize PIM-1 Protein Function and Its Interaction With PI3K/Akt/mTOR Pathway Regulated by Its Active Sites Through FRET Biosensors","authors":"Na Li,&nbsp;Youyi Zhao,&nbsp;Danbo Wang,&nbsp;Shuai Shao,&nbsp;Zhengyao Zhang,&nbsp;Bo Liu","doi":"10.1002/biot.202400443","DOIUrl":"10.1002/biot.202400443","url":null,"abstract":"<div>\u0000 \u0000 <p>Pro-viral Insertion site for the Moloney Murine Leukemia virus 1 (PIM-1) is widely involved in various biological processes and diseases, which is based on its structure and functional sites. However, the relationship between active sites and function of PIM-1 kinase remains unclear due to the lack of effective study approaches in live cells. Herein, to visualize the effect of different active sites in PIM-1 protein on its function activity and relation with PI3K/Akt/mTOR pathway, three mutant probes of EPHY which was developed previously based on fluorescence resonance energy transfer (FRET) technology to detect PIM-1 kinase activity in living cells were further constructed and transfected into cells followed by treating with PIM-1 inhibitors, ATP and PI3K inhibitor, respectively. The results showed that Lys67 is related to substrate binding and catalytic activity of PIM-1 kinase, thereby directly regulating PI3K/Akt/mTOR signaling pathway. Pro81/Asn82 are primarily participated in PIM-1 binding to ATP, thus also involving in the modulation on PI3K/Akt/mTOR signaling pathway, but play less role in the interaction between PIM-1 protein and its substrate. Asp167 has few effects on both the catalytic function activity of PIM-1 and PI3K/AKT/mTOR pathway, even though the binding ability of PIM-1 protein to its substrate is dramatically inhibited by D167A mutation. Altogether, the mutant probes works well as visualization tools to unearth the function of active sites in PIM-1 kinase, not only facilitating the further clarification of molecular mechanism underlying PIM-1 related signaling pathways, but also shedding light on drug development and disease therapy targeting PIM-1 protein.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"19 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Considerations Regarding High Oil Density Bioreactor-Scale Fermentations of Yarrowia lipolytica Using CFD Modeling and Experimental Validation","authors":"Sarah M. Coleman,&nbsp;Richard J. Marx,&nbsp;Morgan K. Martinez,&nbsp;Ashli J. Silvera,&nbsp;Junwon Park,&nbsp;Esha Ramanan,&nbsp;Geena Kaown,&nbsp;Seongkyu Yoon,&nbsp;Dongming Xie,&nbsp;Hal S. Alper","doi":"10.1002/biot.202400506","DOIUrl":"10.1002/biot.202400506","url":null,"abstract":"<div>\u0000 \u0000 <p>Hydrophobic feedstocks such as waste cooking oil have recently been considered for microbial biotransformation due to their abundance, low cost, and unique advantage for lipid-derived fermentation products. Most fermentations with hydrophobic substrates are conducted at the tube or flask scale (less than 1 L total volume) or with the hydrophobic substrate comprising a small fraction of the media. Low substrate concentrations require additional feeding. Alternatively, high concentrations do not require significant dilution of the oil feedstock, which reduce volumetric requirements for larger scale fermentations. However, high-oil-density fermentations complicate efficient mixing and mass transfer challenges which are exacerbated at larger scales. To address this, computational fluid dynamics (CFD) models were explored to simulate three-phase (hydrophobic, hydrophilic, and gaseous) bench (3 L) and pilot scale (4000 L) bioreactors, highlighting challenges and potential considerations. Bioreactor fermentations of <i>Yarrowia lipolytica</i> strain L36DGA1 with substrate loadings of 5%, 10%, 20%, 30%, 40%, and 50% (v/v) waste cooking oil were also conducted, representing one of the highest concentrations in the reported literature. This work supports future research into and implementation of high-oil-density fermentations at the bench and pilot bioreactor scale.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"19 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Creating a System of Dual Regulation of Translation and Transcription to Enhance the Production of Recombinant Protein","authors":"Xin Li,&nbsp;Peng-Wei Shi,&nbsp;Fei Du,&nbsp;Zi-Xu Zhang,&nbsp;Zi-Jia Li,&nbsp;Na Wu,&nbsp;Guang Yang,&nbsp;Wang Ma,&nbsp;Xiao-Man Sun","doi":"10.1002/biot.202400679","DOIUrl":"10.1002/biot.202400679","url":null,"abstract":"<div>\u0000 \u0000 <p>When constructing cell factories, it is crucial to reallocate intracellular resources towards the synthesis of target compounds. However, imbalanced resource allocation can lead to a tradeoff between cell growth and production, reducing overall efficiency. Reliable gene expression regulation tools are needed to coordinate cell growth and production effectively. The orthogonal translation system, developed based on genetic code expansion (GCE), incorporates non-canonical amino acids (ncAAs) into proteins by assigning them to expanded codons, which enables the control of target protein expression at the translational level in an ncAA-dependent manner. However, the stringency of this regulatory tool remains inadequate. This study achieved strict translational-level control of the orthogonal translation system by addressing the abnormal leakage caused by the arabinose-inducible promoter. Further validation was conducted on the relationship between ncAA concentration and expression level, as well as the host's adaptability to the system. Subsequently, the system's applicability across multiple <i>Escherichia coli</i> hosts was verified by examining the roles of RF1 (peptide chain release factor 1) and endogenous TAG codons. By combining this strategy with inducible promoters, dual-level regulation of target gene expression at both transcriptional and translational levels was achieved and the dynamic range was further increased to over 20-fold. When using ncAA to control the expression of T7 RNA polymerase (T7 RNAP), the leakage expression was reduced by 82.7%, mitigating the low production efficiency caused by extensive leakage in the T7 system. As proof of concept, the strategy enhanced the production of alcohol dehydrogenase (ADH) by 9.82-fold, demonstrating its excellent capability in controlling gene expression in developing cell factories.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"19 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information: Biotechnology Journal 12/2024","authors":"","doi":"10.1002/biot.202470121","DOIUrl":"https://doi.org/10.1002/biot.202470121","url":null,"abstract":"","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"19 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biot.202470121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Competition-Based Strategy for the Isolation of an Anti-Idiotypic Blocking Module and Fine-Tuning for Conditional Activation of a Therapeutic Antibody","authors":"Jan Habermann,&nbsp;Dominic Happel,&nbsp;Adrian Bloch,&nbsp;Charles Shin,&nbsp;Harald Kolmar","doi":"10.1002/biot.202400432","DOIUrl":"10.1002/biot.202400432","url":null,"abstract":"<p>The masking of therapeutic antibodies by the installation of a blocking module that can be removed under certain physiological conditions, is becoming increasingly important to improve their safety and toxicity profile. To gain access to such masking units, we used chicken immunization in combination with yeast surface display and a competition-based FACS screening campaign to obtain anti-idiotypic single-chain Fv (scFv) fragments. This approach promotes the identification of functional masking units, since specificity and high affinity do not necessarily guarantee a paratope blocking effect. This strategy was used to isolate a scFv masking unit for the therapeutic antibody 6G11 (BI-1206), which is currently in clinical trials for the treatment of B-cell lymphoma to block the inhibitory Fcγ receptor IIB (CD32b). N-terminal fusion of the anti-idiotypic scFv to the 6G11 light chain successfully abolished binding to FcγRIIB in vitro. For conditional activation, a cleavable linker for the tumor-associated protease MMP-9 was implemented. To improve demasking efficiency, the affinity of the scFv mask was attenuated through rational design. The substitution of one key amino acid in the masking scFv reduced the affinity toward the 6G11 paratope by factor 10 but still mediated 9800-fold blocking of receptor binding. Proteolytic demasking allowed full recovery of therapeutic antibody function in vitro, supporting the concept of conditional antibody activation using this anti-idiotypic binding module.</p>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"19 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}